Drug Carriers

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Nanotechnology is playing an increasing role in targeted drug delivery into pathological tissues. Drug-loaded pharmaceutical nanocarriers can be delivered into diseased sites by passive targeting (spontaneous accumulation of nanocarriers in the areas with affected vasculature) or by active targeting (via site-specific ligands attached to the surface of drug-loaded nanocarriers). Subsequent level of targeting requires cellular internalization of nanocarriers and their specific association with certain individual cell organelles. The control over intracellular distribution of pharmaceutical nanocarriers requires effective and non-invasive methods of their visualization inside cells. In an attempt to enhance cellular internalization of pharmaceutical nanocarriers and their association with mitochondria specifically, we have prepared three types of cationic liposomes and investigated their intracellular distribution. The analysis was performed using Raman microspectroscopy in combination with optical microscopy, in order to provide morphological information as well as biochemical signatures of the sample. It was demonstrated that the Raman microscopy allows to evaluate the extent of mitochondrial association depending on the liposome composition.

empty liposomes CPP coronary perfusion pressure LV left ventricle LVDP left ventricular developed pressure LVEDP left ventricular end diastolic pressure LVSP left ventricular systolic pressure KH Krebs-Henseleit EPR enhanced permeability and retention Rh-PE rhodamine-phosphatidylethanolamine FITC-dextran fluorescein-isothiocyanate-labeled dextran PEG poly(ethylene glycol

Previously, stearyl triphenylphosphonium (STPP)-modified liposomes (STPP-L) were reported to target mitochondria. To overcome a non-specific cytotoxicity of STPP-L, we synthesized a novel polyethylene glycol-phosphatidylethanolamine (PEG-PE) conjugate with the TPP group attached to the distal end of the PEG block (TPP-PEG-PE). This conjugate was incorporated into the liposomal lipid bilayer, and the modified liposomes were studied for their toxicity, mitochondrial targeting, and efficacy in delivering paclitaxel (PTX) to cancer cells in vitro and in vivo. These TPP-PEG-PE-modified liposomes (TPP-PEG-L), surface grafted with as high as 8 mole % of the conjugate, were less cytotoxic compared to STPP-L or PEGylated STPP-L. At the same time, TPP-PEG-L demonstrated efficient mitochondrial targeting in cancer cells as shown by confocal microscopy in co-localization experiments with stained mitochondria. PTX-loaded TPP-PEG-L demonstrated enhanced PTX-induced cytotoxicity and anti-tumor efficacy in cell culture and mouse experiments compared to PTX-loaded unmodified plain liposomes (PL). Thus, TPP-PEG-PE can serve as a targeting ligand to prepare non-toxic liposomes as mitochondria-targeted drug delivery systems (DDS).

Eudraginated polymer blends: A potential oral controlled drug delivery system for theophylline Sustained release (SR) dosage forms enable prolonged and continuous deposition of the drug in the gastrointestinal (GI) tract and improve the bioavailability of medications characterized by a narrow absorption window. In this study, a new strategy is proposed for the development of SR dosage forms for theophylline (TPH). Design of the delivery system was based on a sustained release formulation, with a modified coating technique and swelling features aimed to extend the release time of the drug. Different polymers, such as Carbopol 71G (CP), sodium carboxymethylcellulose (SCMC), ethylcellulose (EC) and their combinations were tried. Prepared matrix tablets were coated with a 5 % (m/m) dispersion of Eudragit (EUD) in order to get the desired sustained release profile over a period of 24 h. Various formulations were evaluated for micromeritic properties, drug concentration and in vitro drug ...

Due to tenoxicam (TX)'s poor aqueous solubility (0.072 mg/ml), it is poorly absorbable in the GIT, and the long-term oral administration of TX may cause severe GIT disturbances. Topical administration of TX can help in bypassing the GIT adverse effects. Therefore, in the present work, we constructed different pluronic/lecithin organogels (PLOs) for topical delivery of TX. PLO was constructed simply via direct mixing of an aqueous pluronic solution with lecithin solution. The prepared PLO formulations were characterized for their physicochemical properties including pH, drug content, visual inspection, viscosity, and spreadability. Also, the in vitro release and kinetic studies were carried out to investigate the mechanism of drug release. Moreover, the in vivo studies were carried out by investigating the anti-inflammatory and analgesic activities using albino male rats. The results showed that the modified PLOs have good physicochemical properties. The viscosity of the modified gels is a direct proportionality with both lecithin and pluronic concentrations. Also, subsequently, the drug release rate is directly proportional to gel viscosity. Moreover, the in vivo studies showed that the modified PLOs (F19) showed a significant (< 0.05%) paw edema inhibition and pain analgesia compared with other investigated groups. Also, the results indicated that the increase in dose is accompanied by higher activity and a longer duration of action which extended to 12 h. Hence, the modified PLOs are promising safe candidates or vehicles for effective TX loading with sustained delivery behavior.

Chitosan (CH) is a natural product produced from the shells of crustaceans. Both CH and Chitosan nanoparticles (CH-NPs) have recently been used in various pharmaceutical and biomedical applications. The present study aimed to evaluate the potency of chitosan or chitosan nanoparticles in reducing the negative effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)induced haematotoxicity and nephrotoxicity in albino rats. Methods: Twenty adult male albino rats were placed in four groups of five rats each: the control group, the TCDD group (10µg/kg intraperitoneally injected), the TCDD + CH group (intraperitoneal injection of TCDD (10µg/ kg) and an oral dose of CH (200 mg/kg), and the TCDD + CH-NPs group: intraperitoneal injection of a dose of TCDD (10µg/ kg) and an oral dose of CH-NPs (200 mg/kg). For all groups, the experimental period lasted for four weeks. Results: The TCDD-treated group showed a significant (P < 0.05) decrease in RBC count, HB, HCT, WBC count, lymphocyte percentage, and PLT, whereas there was a non-significant decrease in MCV, MCH, MCHC, and monocytes. On the other hand, a significant increase in neutrophils and eosinophils was noticed. In addition, several morphological abnormalities in the erythrocyte membranes were observed in the TCDD-treated group. A significant increase in serum urea and creatinine levels and marked histopathological changes in kidney tissue were observed. Administration of chitosan and chitosan nanoparticles could approximately restore the normal hematological parameters and improve the dioxin-induced renal histopathological changes. Although there is no significant difference between CH and CH-NPs groups, CH have seemed to have a better effect on some parameters and vice versa with CH-NPs in some parameters. The present study concluded that oral administration of CH or CH-NPs to the TCDD-treated animals might play a protective role against dioxin-induced hematotoxicity and nephrotoxicity in rats.

Although resistant starch/pectin (RS/P) films have previously displayed suitable properties for colonspecific drug delivery, nanocomposite films were developed aiming to enhance physicochemical, thermal, mechanical and barrier properties, as well as the low oral bioavailability of methotrexate (MTX). FEG-SEM micrographs of nanocomposite films showed different interaction patterns occurring among nanocellulose and RS/P. The nanofiller addition led to an increase in the thermal stability, probably due to its interaction with RS crystalline double helices. Results also displayed an improvement of the puncture strength, while barrier properties revealed a low water vapor permeability. Ex vivo bioadhesion test displayed the nanocomposites films to interact strongly with porcine gastrointestinal mucosa. In vitro drug release studies showed that the films developed enhanced the drug dissolution rates with approximately 80% of MTX release in 150 min, suggesting the potential of these materials as a poor solubility drugs carrier, which constitutes an important tool for enhancing oral bioavailability.

Self-assembly of multidomain peptides (MDP) can be tailored to carry payloads that modulate the extracellular environment. Controlled release of growth factors, cytokines, and small-molecule drugs allows for unique control of in vitro and in vivo responses. In this study, we demonstrate this process of ionic cross-linking of peptides using multivalent drugs to create hydrogels for sustained long-term delivery of drugs. Using phosphate, heparin, clodronate, trypan, and suramin, we demonstrate the utility of this strategy. Although all multivalent anions result in good hydrogel formation, demonstrating the generality of this approach, suramin led to the formation of the best hydrogels per unit concentration and was studied in greater detail. Suramin ionically cross-linked MDP into a fibrous meshwork as determined by scanning and transmission electron microscopy. We measured material storage and loss modulus using rheometry and showed a distinct increase in G&#39; and G″ as a function ...

Paclitaxel is hydrophobic in nature and is recognized as a highly toxic anticancer drug, showing adverse effects in normal body sites. In this study, we developed a polymeric nano drug carrier for safe delivery of the paclitaxel to the cancer that releases the drug in a sustained manner and reduces side effects. N-isopropylacrylamide/ vinyl pyrrolidone (NIPAAm/VP) nanoparticles were synthesized by radical polymerization. Physicochemical characterization of the polymeric nanoparticles was conducted using dynamic light scattering, transmission electron microscopy, scanning electron microscopy and nuclear magnetic resonance, which confirmedpolymerization of formulated nanoparticles. Drug release was assessed using a spectrophotometer and cell viability assays were carried out on the MCF-7 breast cancer and B16F0 skin cancer cell lines. NIPAAm/ VP nanoparticles demonstrated a size distribution in the 65-108 nm range and surface charge measured -15.4 mV. SEM showed the nanoparticles to be spherical in shape with a slow drug release of ~70% in PBS at 38°C over 96 h. Drug loaded nanoparticles were associated with increased viability of MCF-7 and B16F0 cells in comparison to free paclitaxel. Nano loaded paclitaxel shows high therapeutic efficiency by sustained release action for the longer period of time, i increasing its efficacy and biocompatibility for human cancer therapy. Therefore, paclitaxel loaded (NIPAAm/VP) nanoparticles may provide opportunities to expand delivery of the drug for clinical selection.

We explored the duration of immune responses and the effect of a late third HIV-modified vaccinia virus Ankara (MVA) boost in HIV-DNA primed and HIV-MVA boosted Tanzanian volunteers. Twenty volunteers who had previously received three HIV-DNA and two HIV-MVA immunizations were given a third HIV-MVA immunization 3 years after the second HIV-MVA boost. At the time of the third HIV-MVA, 90% of the vaccinees had antibodies to HIV-1 subtype C gp140 (median titer 200) and 85% to subtype B gp160 (median titer 100). The majority of vaccinees had detectable antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, 70% against CRF01_AE virus-infected cells (median titer 239) and 84% against CRF01_AE gp120-coated cells (median titer 499). A high proportion (74%) of vaccinees had IFN-γ ELISpot responses, 63% to Gag and 42% to Env, 3 years after the second HIV-MVA boost. After the third HIV-MVA, there was an increase in Env-binding antibodies and ADCC-mediating antibodies relative to...

ES participated in the design of the study. FSM and MB oversaw the implementation of the study. JF, LM, EAA and MJ participated in the conduct of the study. BW and AB designed and constructed the DNA vaccines and performed preclinical studies leading to selection of the HIVIS DNA vaccines. DB served on the oversight of dispensing DNA and MVA vaccines, accountability and treatment allocation. SA, EFL, CN, AJ, VP, KGR, FSM and GB were responsible for the immunological assays and SA, EFL and FSM were responsible for the safety assays. CM and ES undertook statistical analyses. MB, SA, CN, GB, FSM and ES drafted the report and all co-authors participated in revising the report.

International Journal of ChemTech Research CODEN( USA): IJCRGG ISSN : 0974-4290 Vol.1, No.4, pp 941-947, Oct-Dec 2009 ... Amrish Kumar*1, Pankaj Sharma1, Ashwani Chaturvedi1, Durga Jaiswal1, Meenakshi Bajpai1, Mukesh Choudhary2, Indranil Kumar ...

Superparamagnetic iron oxide nanoparticles (MNPs) with appropriate surface chemistry exhibit many interesting properties that can be exploited in a variety of biomedical applications such as magnetic resonance imaging contrast enhancement, tissue repair, hyperthermia, drug delivery and in cell separation. These applications required that the MNPs such as iron oxide Fe3O4 magnetic nanoparticles (Fe3O4 MNPs) having high magnetization values and particle size smaller than 100 nm. This paper reports the experimental detail for preparation of monodisperse oleic acid (OA)-coated Fe3O4 MNPs by chemical co-precipitation method to determine the optimum pH, initial temperature and stirring speed in order to obtain the MNPs with small particle size and size distribution that is needed for biomedical applications. The obtained nanoparticles were characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dis...

Purpose: To compare the intravitreal pharmacokinetic profile of a triamcinolone acetonide formulation containing the preservative benzyl alcohol (TA-BA) versus a preservative-free triamcinolone acetonide formulation (TA-PF), and evaluate potential signs of toxicity to the retina. Methods: A total of 60 New Zealand male white rabbits, divided into two groups, were studied. In the TA-BA group, 30 rabbits received an intravitreal injection of TA-BA (4 mg/0.1ml) into the right eye. In the TA-PF group, 30 rabbits received an intravitreal injection of TA-PF (4 mg/0.1ml) into the right eye. The intravitreal drug levels were determined in 25 animals from each group by high-performance liquid chromatography (HPLC). The potential for toxicity associated with the intravitreal triamcinolone injections was evaluated in five randomly selected animals from each group by electroretinography (ERG) and by light microscopy.

Background: Textile dyeing is a major environmental pollutant in the fashion industry. Producing naturally colored silk through dietary dye supplementation in silkworms offers a potential eco-friendly alternative. However, the effects of this method on silkworm development, cocoon yield, and silk quality are not fully understood. Aim: This study aimed to evaluate the impact of supplementing mulberry leaves with different dyes on silkworm (Bombyx mori) growth, cocoon yield, and the quality and coloration of silk cocoons. Methods: An experiment was conducted using a completely randomized design with three replicates, each containing 200 fourth-instar silkworms. Three dyes (rhodamine B, Nile blue A, and neutral red) and a control (freshwater) were applied to mulberry leaves. Parameters recorded included larval development duration, larvae and silk gland weight, pupation rate, single cocoon and shell weight, total cocoon yield, filament length, raw silk rate, and silk color. Results: Dye supplementation resulted in visible coloration in larvae, silk glands, and cocoons. Compared to the control, dye treatments caused a reduction of 4%-13% in single cocoon weight and 17.4%-26% in shell weight. Cocoon yield per 200 larvae decreased by 19.3%-29.4%. Among the dyes, neutral red produced the highest yield, while rhodamine yielded the longest silk filament. The dyed cocoons retained distinguishable colors, although lighter than the original dyes, with minor adverse effects on silk quality. Conclusion: Feeding silkworms with dye-supplemented mulberry leaves successfully produced naturally colored silk with minimal negative effects on development and quality. This approach represents a promising, environmentally sustainable method for producing high-value colored silk.

Eukaryotic life contains hierarchical vesicular architectures (i.e. organelles) that are crucial for material production and trafficking, information storage and access, as well as energy production. In order to perform specific tasks, these compartments differ among each other in their membrane composition and their internal cargo and also differ from the cell membrane and the cytosol. Man-made structures that reproduce this nested architecture not only offer a deeper understanding of the functionalities and evolution of organelle-bearing eukaryotic life but also allow the engineering of novel biomimetic technologies. Here, we show the newly developed vesicle-in-water-in-oil emulsion transfer preparation technique to result in giant unilamellar vesicles internally compartmentalized by unilamellar vesicles of different membrane composition and internal cargo, i.e. hierarchical unilamellar vesicles of controlled compositional heterogeneity. The compartmentalized giant unilamellar vesicles were subsequently isolated by a separation step exploiting the heterogeneity of the membrane composition and the encapsulated cargo. Due to the controlled, efficient, and technically straightforward character of the new preparation technique, this study allows the hierarchical fabrication of compartmentalized giant unilamellar vesicles of controlled compositional heterogeneity and will ease the development of eukaryotic cell mimics that resemble their natural templates as well as the fabrication of novel multi-agent drug delivery systems for combination therapies and complex artificial microreactors.

Eukaryotic life contains hierarchical vesicular architectures (i.e. organelles) that are crucial for material production and trafficking, information storage and access, as well as energy production. In order to perform specific tasks, these compartments differ among each other in their membrane composition and their internal cargo and also differ from the cell membrane and the cytosol. Man-made structures that reproduce this nested architecture not only offer a deeper understanding of the functionalities and evolution of organelle-bearing eukaryotic life but also allow the engineering of novel biomimetic technologies. Here, we show the newly developed vesicle-in-water-in-oil emulsion transfer preparation technique to result in giant unilamellar vesicles internally compartmentalized by unilamellar vesicles of different membrane composition and internal cargo, i.e. hierarchical unilamellar vesicles of controlled compositional heterogeneity. The compartmentalized giant unilamellar vesicles were subsequently isolated by a separation step exploiting the heterogeneity of the membrane composition and the encapsulated cargo. Due to the controlled, efficient, and technically straightforward character of the new preparation technique, this study allows the hierarchical fabrication of compartmentalized giant unilamellar vesicles of controlled compositional heterogeneity and will ease the development of eukaryotic cell mimics that resemble their natural templates as well as the fabrication of novel multi-agent drug delivery systems for combination therapies and complex artificial microreactors.

Objectives-Report of risk behavior, HIV incidence, and pregnancy rates among women participating in the Step Study, a phase IIB trial of MRKAd5 HIV-1 gag/pol/nef vaccine in HIVnegative individuals who were at high risk of HIV-1. Methods-Women were from North American (NA) and Caribbean and South America (CSA) sites. Risk behavior was collected at screening and 6-month intervals. Differences in characteristics between groups were tested with Chi-square, two-sided Fisher's exact tests, and Wilcoxon rank sum tests. Generalized estimating equation models were used to assess behavioral change. Results-Among 1134 enrolled women, the median number of male partners was 18; 73.8% reported unprotected vaginal sex, 15.9% unprotected anal sex and 10.8% evidence of a sexually

We report herein a biopolymer actuator with a modular design that allosterically transduces ligand binding into an aqueous demixing phase transition. The biopolymer actuator consists of two modular domains: a ligand binding protein domain, calmodulin (CaM) that is fused to a transducer domain, a stimulus responsive elastin-like polypeptide (ELP) that exhibits a reversible lower critical solution temperature (LCST) phase transition. We demonstrate that binding of calcium to CaM spontaneously triggers the phase transition of the attached ELP, leading to the formation of meso-micro scale particles depending on the chain length of the ELP. This behavior is reversible, as chelation of the bound calcium results in dissolution of the assembled particles; is selective for calcium as opposed to magnesium; and is abolished by the binding of a peptide ligand that is specific to calcium-bound CaM. These results are, to our knowledge, the first demonstration of biomolecular recognition triggered, allosteric regulation of the LCST phase transition of a polymer, and are significant because they expand the available triggers of the LCST transition of stimulus responsive polymers to biochemical ligand binding. The ability to allosterically trigger the LCST transition of ELPs by biomolecular recognition will be useful for developing "smart" polymer actuators that capitalize upon the myriad ligand-protein pairs that are available from biology, for application in the design of selective pull-down assays in proteomics, drug delivery, and in the design of nanoscale biomolecular devices.

2. From Ringsdorf's model to the clinic: current status of polymer-drug conjugates 2.1. Polymer conjugates carrying orthodox anticancer agents 2.1.1. Polymer-Dox conjugates 2.1.2. Polymer-paclitaxel conjugates 2.1.3. Polymer-camptothecin conjugates 2.1.4. Polymer-platinate conjugates 2.2. Polymer-anticancer drug conjugates designed for active targeting 3. Polymer-drug conjugates: future trends, challenges and opportunities 3.1. Novel polymers and polymer architecture, implications for intracellular targeting 3.2. A novel concept in polymer-drug conjugates: drug combination 3.3. Polymer conjugates carrying novel anticancer agents 3.4. Use of polymer-drug conjugates for the treatments of diseases other than cancer 3.5. The importance of an exhaustive physico-chemical characterization of polymer-drug conjugates 4. Conclusions 5. Acknowledgments 6. References

Polymeric nanoparticles have revealed very effective in transmucosal delivery of proteins. Polysaccharides are among the most used materials for the production of these carriers, owing to their structural flexibility and propensity to evidence biocompatibility and biodegradability. In parallel, there is a preference for the use of mild methods for their production, in order to prevent protein degradation, ensure lower costs and easier procedures that enable scaling up. In this work we propose the production of pullulan-based nanoparticles by a mild method of polyelectrolyte complexation. As pullulan is a neutral polysaccharide, sulfated and aminated derivatives of the polymer were synthesized to provide pullulan with a charge. These derivatives were then complexed with chitosan and carrageenan, respectively, to produce the nanocarriers. Positively charged nanoparticles of 180-270 nm were obtained, evidencing ability to associate bovine serum albumin, which was selected as model protein. In PBS pH 7.4, pullulan-based nanoparticles were found to have a burst release of 30% of the protein, which maintained up to 24h. Nanoparticle size and zeta potential were preserved upon freeze-drying in the presence of appropriate cryoprotectants. A factorial design was approached to assess the cytotoxicity of raw materials and nanoparticles by the metabolic test MTT. Nanoparticles demonstrated to not cause overt toxicity in a respiratory cell model (Calu-3). Pullulan has, thus, demonstrated to hold potential for the production of nanoparticles with an application in protein delivery.

This mini review explores the integration of venom-derived bioactives with nanotechnology for targeted cancer therapy. Venom peptides such as melittin, apamin, and chlorotoxin exhibit potent cytotoxicity against cancer cells but suffer from poor stability and off-target toxicity. Recent advances in nanoparticle-based delivery systems—liposomes, polymeric carriers, and metallic nanoparticles—have enabled controlled release, tumor-specific targeting, and enhanced therapeutic efficacy. We synthesize findings from four recent studies that demonstrate the promise of venom-loaded nanomaterials in treating breast, glioma, and colon cancers. These insights support the development of precision nanomedicine platforms that harness venom’s natural potency while minimizing systemic toxicity.

Epithelial ovarian cancer (EOC) is a lethal gynecological neoplasia characterized by extensive angiogenesis and overexpression of nerve growth factor (NGF). Here, we investigated the mechanism by which NGF increases vascular endothelial growth factor (VEGF) expression and the vasculogenic potential of EOC cells, as well as the contribution of the cyclooxygenase 2/prostaglandin E2 (COX-2/PGE2) signaling axis to these events. EOC biopsies and ovarian cell lines were used to determine COX-2 and PGE2 levels, as well as those of the potentially pro-angiogenic proteins c-MYC (a member of the Myc transcription factors family), survivin, and β-catenin. We observed that COX-2 and survivin protein levels increased during EOC progression. In the EOC cell lines, NGF increased the COX-2 and PGE2 levels. In addition, NGF increased survivin, c-MYC, and VEGF protein levels, as well as the transcriptional activity of c-MYC and β-catenin/T-cell factor/lymphoid enhancer-binding factor (TCF-Lef) in a T...

SLNs are hopeful carriers for the topical delivery of antifungal drugs. This research aimed to develop a topical gel combining Efinaconazole-loaded SLNs with fluconazole to enhance the treatment of onychomycosis. The objective was to formulate a nail gel that capitalizes on the localized action and improved adherence of efinaconazole, a crucial agent in treating nail disorders like onychomycosis. The formulation utilized an alcohol-based system with specialized ingredients to ensure low surface tension and optimal wetting properties. Fluconazole, a broad-spectrum third-generation triazole antifungal, was included for its systemic and superficial antifungal activity. It works by inhibiting the formation of ergosterol, a key component of fungal cell membranes, by blocking the fungal cytochrome P-450 enzyme. The SLN-based delivery system allows for the slower release of Efinaconazole, while fluconazole diffuses more rapidly. The optimized gel formulation showed sustained drug release, with Efinaconazole releasing 32.85% of the drug by the 8 th hour, compared to 74.05% for fluconazole during the same period. A stability study on the F4 formulation, which utilized Carbopol 934, was conducted according to ICH guidelines and demonstrated that the gel maintained its quality attributes, such as color, odor, homogeneity, pH, and viscosity over 6 months of testing. These results indicate that the F4 topical gel formulation is stable and suitable for long-term use.

The study aimed to prepare imatinib mesylate-loaded polybutylcyanoacrylate (PBCA) nanoparticles and evaluate their efficacy on leukemia cell line K562. The formulation was prepared by miniemulsion polymerization technique. Nanoparticles were characterized by dynamic light scattering (DLS), spectrophotometry, Fourier transform infrared spectroscopy (FTIR), dialysis membrane, and 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) techniques. Nanoscale particles with high encapsulation efficiency (86%) and physical entrapment of drug were observed. In addition, nanoparticles showed suitable drug retention capability and potentiate the cytotoxicity effects of imatinib mesylate. Findings of study suggested PBCA nanoparticles are promising carrier for imatinib mesylate delivery to leukemia cell line K562.

Nowadays bacterial resistance to known antibiotics is a serious health problem. In order to achieve more efficient treatment, lately there is an effort to find new substances, such as certain biomaterials, that are non-toxic to humans with antibiotic potential. Lignins and lignin-derived compounds have been proposed to be good candidates for use in medicine and health maintenance. In this study, the antibacterial activity of the lignin model polymer dehydrogenate polymer (DHP) in alginate hydrogel (Alg) was studied. The obtained results show that DHP-Alg has strong antimicrobial activity against several bacterial strains and biofilms and does not have a toxic effect on human epithelial cells. These results strongly suggest its application as a wound healing agent or as an adjunct substance for wound treatments.

In order to meet the unmet medical needs for effective cancer treatment, multifunctional nanocarriers based on iron oxide nanoparticles hold tremendous promise. Here we report a superparamagnetic iron oxide nanoparticles based hexa-functional nanosystem for synergistic cancer theranostic applications by offering active tumour targeting, accumulation and complementary imaging capability by combining magnetic resonance imaging as well as near-infrared fluorescence, magnetophotothermia and chemotherapy. The uniquely designed nanosystem exhibited a paramount increase in the antitumour efficacy through the simultaneous application of multiple thermal effects called magnetophotothermia, which outweighed the therapeutic efficacy of the current thermo-chemo therapies or stand-alone therapies. The active tumour-seeking property with prolonged tumour accumulation and complementary imaging capability with improved sensitivity and resolution also augments the therapeutic efficacy of the propose...

Quantitative evaluation of the effect caused by vaginal administration of gelatin capsules loaded with starch pellets and lyophilized powder, respectively, on vaginal pH and microflora. Method: Administration of gelatin capsules loaded with fast-disintegrating starch pellets (group P) or lyophilized lactose/skimmed milk (group L) was compared to no intervention (group C) in a 3-way randomized, double-blinded, parallel study with 18 volunteers. Follow-up visits were at day 6 (immediately after administration), day 14 (pill stop), day 22 (after withdrawal bleeding) and day 35 (midcycle). Vaginal pH was measured and swabs were taken for Gram staining and culture to assess the presence of hydrogen peroxide-producing lactobacilli. Colposcopy was performed to assess the occurrence of adverse effects on the vaginal and ectocervical mucosa. Results: No severe adverse events occurred. For all women, vaginal pH and Gram stain were normal from screening until pill stop. Although immediately after withdrawal bleeding, 8 out of 18 women had an elevated pH, a disturbed microflora or lacked hydrogen peroxide-producing lactobacilli, all women had hydrogen peroxide-producing lactobacilli and a normal vaginal pH at midcycle, and all but two had a normal Gram stain. Conclusion: No major differences could be observed between the groups, whereby all changes in pH and microflora could be ascribed to withdrawal bleeding, indicating that gelatin capsules, starch pellets and lyophilized powder are acceptable carrier materials for the vaginal delivery of probiotic strains.

While administration of medical aerosols with heliox and positive airway pressure are both used clinically to improve aerosol delivery, few studies have differentiated their separate roles in treatment of asthmatics. The aim of this randomized, double blinded study is to differentiate the effect of heliox and oxygen with and without positive expiratory pressure (PEP), on delivery of radiotagged inhaled bronchodilators on pulmonary function and deposition in asthmatics. 32 patients between 18 and 65 years of age diagnosed with stable moderate to severe asthma were randomly assigned into four groups: (1) Heliox þ PEP (n Z 6), (2) Oxygen þ PEP (n Z 6), (3) Heliox (n Z 11) and (4) Oxygen without PEP (n Z 9). Each group received 1 mg of fenoterol and 2 mg of ipratropium bromide combined with 25 mCi

Objectives This study aimed to investigate the distribution and release profile in the skin of a lipophilic model molecule, octylmethoxycinnamate (OMC), loaded in poly(ε-caprolactone) nanocapsules (NC) by the Franz cell method. Methods Nanocapsules were formulated in a hydroxyethylcellulose gel and compared to the same gel containing 5% of free OMC as control. A new extraction method was used to discriminate the OMC still entrapped in the NC from free OMC released in the skin strata. The OMC extraction from the skin was performed using acetonitrile, which broke the NC, or isopropyl myristate, which kept the NC intact. Key findings When isopropylmyristate was used to determine the OMC released from NC, the results showed that more than 80% of the OMC was released from the NC at the skin surface after 6 h, whereas only 30% was released in the stratum corneum and epidermis. Conclusions It is suggested that the mechanism of release is different at the surface and in viable skin, probabl...

Diosmin (DSN) showed poor water solubility and decreased bioavailability. The current study aims to repurpose diosmin-loaded nanoparticles to provide an alternative for the cure of acetic acid (AA)-induced colitis in rats comparing it with the free drug. Lipid-chitosan hybrid nanoparticles (LCHNps) loaded with DSN were prepared and characterized regarding DSN entrapment efficiency, size, and zeta-potential. Additionally, solid-state characterization, in vitro release, and storage stability for the optimized formula were assessed. The anti-inflammatory and antioxidant impact against AA-induced colitis in rodents was further proven. Rats were divided into six groups where acetic acid (2 mL, 3 % v/v) was injected intrarectally on day 4 to cause colitis. DSN and LCHNPs were given orally for 7 days. Colon weight, weight/length ratio, DAI, serum LDH, CRP, ALT, MDA, GSH, colonic necroinflammatory alterations, caspase-1 expression levels, colonic NLRP3, and IL-1β levels were determined. Examination by Transmission electron microscopy (TEM) showed nanoscopic spherical particles. The results of solid-state characterization revealed that the chosen nanoparticles comprised encapsulated drug. DSN-loaded LCHNps alleviated AA-induced colitis via ameliorating colonic histopathological architecture combined with lowering colonic weight, weight/length ratio, DAI and serum LDH, ALT, and CRP levels compared to a free drug formulation. It also counteracted AA-induced colitis via ameliorating oxidative stress (lowering MDA, increasing GSH), and decreasing NLRP3, caspase-1, and IL-1β expression levels. Results showed that DSN-loaded LCHNps can be repurposed to prevent AA-induced colitis in rats.

Determining thermal properties and morphology seems to be useful in the analysis of release and degradation processes form polymeric materials. Risperidone is available in the formulation of a long-acting injection based on poly(D,L-lactide-co-glycolide). Currently, alternative solutions are also offered, i.e., nano- and microparticles or implants, including copolymers of lactide and glycolide. The effect of risperidone content on the properties of poly(L-lactide-co-glycolide) matrices was determined. The study also involved an assessment of the changes during degradation. Risperidone free matrices and the matrices with risperidone were obtained by solvent casting. Thermal characteristics were tested by means of differential scanning calorimetry, and the morphology was evaluated using a scanning electron microscope. Risperidone did not change significantly semi-crystalline structure of poly(L-lactide-co-glycolide) matrices. The decrease in crystallization temperature and glass trans...

Microsponge refers to a highly cross-linked particle system with a capacity to adsorb (like a dry sponge) pharmaceutical materials. There are various methods available to prepare microsponge formulations, in this study we used quasi emulsion-solvent diffusion method with a combination of hydrophobic (ethyl cellulose) and hydrophilic polymers (hydroxypropyl methylcellulose) mediated via Tween 80 and polyvinyl alcohol. Various ratios and amounts of the polymers and surfactants were used to prepare microsponge formulations using ketoprofen as a model drug and extensively characterised. Our results, for the first time, indicate successful and optimised formulation with desired pharmaceutical characteristics using a combination of hydrophobic and hydrophilic polymers.

Remodeling and in vitro erosion of the PEA fibrils (4 mm in length and 120-300 μm in diameter) were analyzed by incubation at 37o C in PBS, human, and rabbit vitreous. In vivo biocompatibility and degradation were analyzed by subconjunctival (sc) and ivt implantation in normal and VEGF-treated rabbits. VEGF injection simulates bloodretinal barrier breakdown characteristic for many diseases of the posterior segment. The animals were regularly funduscopically controlled including an intraocular pressure (IOP) measurement. After finalization the ocular tissue was histologically examined. Changes in molecular weight and mass were determined by GPC in THF and weighing. HPLC measurements determined drug release by single PEA and PLGA fibrils loaded with dexamethasone in vitro. Slow-release intraocular drug delivery by injectable PEA microfibrils G. Thumann1, G. Mihov2, J. Thies2, A. Kemp2, K.M. Morawa1, M. Kropp1 1Dept. Ophthalmology, University Hospitals of Geneva, Switzerland; 2DSM, Gel...

Poly-l-glutamic acid (PG) has been used widely as a carrier to deliver anticancer chemotherapeutics. This study evaluates PG as a selective renal drug carrier. (3)H-deoxycytidine-labeled PGs (17 or 41 kDa) and (3)H-deoxycytidine were administered intravenously to normal rats and streptozotocin-induced diabetic rats. The biodistribution of these compounds was determined over 24 h. Accumulation of PG in normal kidneys was also tracked using 5-(aminoacetamido) fluorescein (fluoresceinyl glycine amide)-labeled PG (PG-AF). To evaluate the potential of PGs in ferrying renal protective anti-oxidative stress compounds, the model drug 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) was conjugated to 41 kDa PG to form PG-AEBSF. PG-AEBSF was then characterized and evaluated for intracellular anti-oxidative stress efficacy (relative to free AEBSF). In the normal rat kidneys, 17 kDa radiolabeled PG (PG-Tr) presents a 7-fold higher, while 41 kDa PG-Tr shows a 15-fold higher renal a...

Objective: The purpose of our study is to search for a new express method for quality control of peptides and polypeptides based on their authenticity. Methods: Aqueous solutions of animal and plant-derived regulatory peptides, experimental compounds and finished therapeutics, finished dosage forms of animal tissue extracts (a mixture of peptides and polypeptides from tissues) and drugs with active pharmaceutical ingredient in which solutions of anti-bodies to interferon γ were applied on a carrier in the fluidized bed chamber have been studied by methods such as: dynamic light scattering (DLS) for determining the size distribution of density heterogeneities, method of two-dimensional dynamic light scattering (2D-DLS) and method for determining radiothermal emission using a broadband radiometer to specific identification of peptides and polypeptides drugs without opening the packaging due to the individual data set of each biomolecule. Method of solid phase peptide synthesis based on the FMOC technology Results: The data obtained indicate that biologically active peptides and polypeptides can induce heterogeneous densities within the submicron (100-1000 nm) and micron (5,000-6,000 nm) ranges. These specific induction patterns were used as individual characteristics of each peptide or active pharmaceutical agent. These were detected using the two-dimensional dynamic light scattering (2D-DLS) method. For example, peptides derived from the same plant (StSys1) and (StPep1) can be easily distinguished at nanomolar concentrations. This approach demonstrates the creation of a unique "fingerprint" for each peptide preparation. In addition, it has been found that solutions containing peptides, which are biologically active nanoparticles with complex shapes, not only emit within the millimeter wavelength range but can also mimic their presence within cells by activating giant clusters. Conclusion: The interaction of peptides and polypeptides with aqueous solutions leads to remote anomalous induction of water clusters. The spectrum of sizes of these giant heterophase water clusters, the kinetics of their flickering, and millimeter-wavelength radio emission open up the possibility of express control of peptide-based drugs by their "authenticity" characteristic without opening the packaging.

Pectin is a natural, non-toxic biopolymer derived from plant cell walls, where it constitutes approximately one-third of the dry weight in most higher plants. Predominantly concentrated in the middle lamella, it has traditionally been used in the food industry for its thickening, gelling, and stabilizing properties. However, its unique resistance to gastric and intestinal enzymatic degradation, coupled with fermentability by colonic bacteria, has led to its emerging role in pharmaceutical applications, particularly in targeted drug delivery. The gelling characteristics of pectin depend on its source, molecular weight, and degree of esterification (DE), factors that influence its suitability as a carrier for bioactive agents. Despite the increasing interest in pectin-based systems, previous reviews have largely focused on its conventional uses, lacking depth in recent advancements within pharmaceutical and biomedical domains. This review addresses those lacunae by offering an updated and detailed examination of pectin's pharmaceutical relevance, with a special focus on pectin beads (PB). It outlines the complete process for preparing the PB formulation, including solution preparation, incorporation of active agents, cross-linking, droplet optimization, hardening, washing, and drying. Furthermore, the article examines the gelation and swelling properties of PB, as well as their morphological and physicochemical characterization using scanning electron microscopy (SEM) and zeta potential analysis. Emphasis is placed on their versatile pharmaceutical applications, such as regulated drug release, colon-specific delivery, iron supplementation, immunization, and enhanced stability via polymeric coatings like chitosan and alginate. By synthesizing current findings, this review provides a comprehensive resource for researchers investigating the potential of pectin in modern therapeutic systems.

The objective of this study was to evaluate the effect of various hydrodynamic conditions on drug release from an eroding and gel forming matrix. For this purpose, dimenhydrinate was formulated with hydroxypropyl methyl cellulose and polyethylene oxide into matrix tablets and the drug release in deionized water was evaluated spectrophotometrically, using multiple dissolution methods, namely, compendial USP 27-apparatus I-III, and a modified apparatus II (paddle over mesh). Various hydrodynamic conditions were examined at the agitation rates of 50 and 100 rpm for apparatus I and II, and 5 and 8 dpm for apparatus III. Similarity and difference factors were calculated using compendial apparatus II release data as reference. Among the methods, apparatus I showed the slowest initial release, while the release from apparatus III at 8 dpm was the highest among the methods. This was further compared via the dissolution half-times and calculation of the average release rate for each method. Based on the analysis of difference and similarity factors (f 1 and f 2 ), the study clearly demonstrates the significance of hydrodynamics and the choice of a dissolution method and their respective effect on overall release profiles when erodible and swellable matrix systems are involved. Full surface exposure with insertion of mesh device in apparatus II may provide more realistic conditions especially when release data are to be used in developing IVIVCs.

The success of pharmacotherapy depends on the availability of the drug at the site of action at a rate that ideally matches the real need in vivo for the duration of therapy. Therefore, pharmacological information such as dose response, onset and duration of effect, as revealed by pharmacokinetic-pharmacodynamic (drug concentrationeffect) relationships, has necessitated attentiveness to and piqued interest in delivering drugs at rates and locations that optimize their effects. Controlled drug delivery, in general, encompasses both rate and location of drug release for achieving beneficial effects and reducing undesired side effects. Design of such delivery systems has evolved and requires expertise in disciplines such as material and polymer sciences, engineering technologies, colloid and surface chemistry, biology, and molecular biopharmaceutics. In this presentation, emphasis is placed on various facets of drug delivery via oral administration, which is the most convenient and preferred means of administration. Novel concepts, experimental and predictive methods, conventional practices, and biosimulation studies for achievements of better delivery systems and more efficacious medication will be discussed.