Papers by Shivakalyani Adepu
International Journal of Molecular Sciences
Drug-eluting stents have been widely implanted to prevent neointimal hyperplasia associated with ... more Drug-eluting stents have been widely implanted to prevent neointimal hyperplasia associated with bare metal stents. Conventional polymers and anti-proliferative drugs suffer from stent thrombosis due to the non-selective nature of the drugs and hypersensitivity to polymer degradation products. Alternatively, various herbal anti-proliferative agents are sought, of which biochanin A (an isoflavone phytoestrogen) was known to have anti-proliferative and vasculoprotective action. PLA-PEG diblock copolymer was tagged with heparin, whose degradation releases heparin locally and prevents thrombosis. To get a controlled drug release, biochanin A was loaded in layered double hydroxide nanoparticles (LDH), which are further encapsulated in a heparin-tagged PLA-PEG copolymer. LDH nanoparticles are synthesized by a co-precipitation process; in situ as well as ex situ loading of biochanin A were done. PLA-PEG-heparin copolymer was synthesized by esterification reaction, and the drug-loaded nanop...
Researchers from the Indian Institute of Technology (IIT) Hyderabad have developed a new drug del... more Researchers from the Indian Institute of Technology (IIT) Hyderabad have developed a new drug delivery system to treat fungal infections, without running the risk of inducing drug resistance
Industrial-scale fabrication and functionalization of nanocellulose
Nanocellulose Materials, 2022
Proceedings of the Indian National Science Academy, 2021
Bacterial cellulose (BC) is a suitable drug delivery carrier owing to the nanofibrous micro and m... more Bacterial cellulose (BC) is a suitable drug delivery carrier owing to the nanofibrous micro and mesoporous structure. One of the unique aspects is the tunability of BC microstructure by the addition of certain additives in the growth medium during the synthesis of cellulose by bacteria. In the present work, BC was in situ modified by adding Polyethylene glycol 2000 (PEG 2000). Effect of in situ modification on crystallinity, chemical composition, microstructure and morphology and, porosity was studied by XRD, FTIR, SEM and BET, followed by the effect on drug (Diclofenac sodium) loading and release kinetics. As a non-incorporating in situ modifier, PEG2000 increased the overall porosity, pore volume and decreased the specific surface area with no significant effect on crystallinity. In vitro, drug release studies revealed that a huge burst release for PEG modified BC as compared to pristine BC. The mechanism of release is further investigated by mathematical modelling. This work opens up avenues of exploring the wide possibility of tuning immediate and sustained drug release from bacterial cellulose for various release applications.
Bacterial Cellulose-Based Drug Delivery System for Dual Mode Drug Release
Transactions of the Indian National Academy of Engineering, 2021
As-produced bacterial cellulose (BC) hydrogel has been dried by two methods [oven drying (OD) and... more As-produced bacterial cellulose (BC) hydrogel has been dried by two methods [oven drying (OD) and freeze drying (FD)] to obtain two different release profiles of the drug diclofenac sodium (DCF). Freeze dried BC exhibits a immediate first order release, while the oven dried BC shows a sustained non-Fickian supercase II transport/release of drug. The difference in the release profiles is due to the difference in the fiber and matrix flexibility, pore size distribution and density. More importantly, this work presents a facile way to obtain a combination of immediate as well as sustained release by a simple assembly of OD and FD BC. It has been shown that the assembled (stacked) sample can offer a burst release for 1 h for immediate pain relief followed by a sustained release for long term pain management. This work can be extended to provide a combinational release of different drugs, where the release profiles need to be different as per their need and activity.
Molecules, 2021
The drug delivery system enables the release of the active pharmaceutical ingredient to achieve a... more The drug delivery system enables the release of the active pharmaceutical ingredient to achieve a desired therapeutic response. Conventional drug delivery systems (tablets, capsules, syrups, ointments, etc.) suffer from poor bioavailability and fluctuations in plasma drug level and are unable to achieve sustained release. Without an efficient delivery mechanism, the whole therapeutic process can be rendered useless. Moreover, the drug has to be delivered at a specified controlled rate and at the target site as precisely as possible to achieve maximum efficacy and safety. Controlled drug delivery systems are developed to combat the problems associated with conventional drug delivery. There has been a tremendous evolution in controlled drug delivery systems from the past two decades ranging from macro scale and nano scale to intelligent targeted delivery. The initial part of this review provides a basic understanding of drug delivery systems with an emphasis on the pharmacokinetics of...
Ex-situ modification of bacterial cellulose for immediate and sustained drug release with insights into release mechanism
Carbohydrate Polymers, 2020
The release of drug from bacterial cellulose (BC) is tuned to achieve immediate and controlled de... more The release of drug from bacterial cellulose (BC) is tuned to achieve immediate and controlled delivery by using two drying strategies: freeze-drying and oven-drying. Diclofenac sodium (DCF), a hydrophilic drug, was used as the model drug and was loaded in oven-dried BC (BC-OD-DCF) and freeze-dried BC (BC-FD-DCF) to obtain sustained release and burst release, respectively. BC dried by the two methods were characterized and found to possess different structures and morphologies. The crystallinity was found to be higher for BC-OD (86 % for BC-OD and 79 % for BC-FD) while BC-FD offered higher porosity (92 % for BC-FD and 75 % for BC-OD), higher specific surface area (85 m2/g for BC-FD and 35 m2/g for BC-OD) and pore size, which altogether affects the matrix swellability, drug loading and release behaviour. The mathematical modelling of drug release kinetics supports diffusion-driven first-order release from BC-FD-DCF whereas release from BC-OD-DCF shows a super case II transport, where the buffer front travels slowly into the denser oven-dried matrix leading to a controlled release of the drug. The correlation between swelling and cumulative drug release is also discussed.
Materialia, 2020
A double barrier release system is designed for herbal essential oils which possess tremendous an... more A double barrier release system is designed for herbal essential oils which possess tremendous anti-fungal activity, even against drug-resistant fungi. However, their utilization is limited owing to their sensitivity towards pH, temperature and light. Three essential oils (thymol, eugenol, carvacrol) are microencapsulated in polylactic acid shell with a high encapsulation efficiency of 80% in order to leverage their synergistic anti-fungal activity. These microcapsules are further incorporated in bacterial cellulose-a naturally produced nanofibrous hydrogel. This unique system offers double barrier to the release of oils-the polymeric shell and the nanofibrous matrix. The anti-fungal testing was carried out on model fungus-Candida albicans (cause of common oral, vaginal infections). In vitro transvaginal drug release study was performed to compare release from microcapsules as colloids and the composites, where the later exhibited a controlled release. Mathematical modelling was performed to understand the release, which is governed by matrix swelling, diffusion of oils and erosion of microcapsules. The time-kill curves show that the composites were able to achieve fungicidal endpoint with half the oil dosage as compared to the colloidal microcapsules and were far more effective than commercial antifungal fluconazole.
Journal of Materials Science, 2017
Bacterial cellulose-based antifouling materials have been produced by incorporation of silver nan... more Bacterial cellulose-based antifouling materials have been produced by incorporation of silver nanoparticles for broad-spectrum antimicrobial activity. Three variations of silver nitrate (AgNO 3) to reducing agent concentrations have been tried to vary the silver nanoparticle dimension. The formation of silver nanoparticles was also evidenced by the X-ray diffraction, and the crystallite size was found to decrease with increase in NaBH 4 concentration. AgBC composites having \ 2% (W/W) of silver exhibited 99.9% antimicrobial activity which was sustained up to 72 h against spoiled food derived mixed microbial culture. On the other hand, only 90% activity was observed with colloidal AgNPs due to aggregate formation. Composites displayed superior antimicrobial activity than colloid with equivalent amount of silver. Food stuff was protected from microbial spoilage for 30 days when stored in AgBC nanocomposites, whereas spoilage was noticed within 15 days for food stuff stored in regular polythene bag. Therefore, the AgBC composite having \ 2% silver can be used as a lining of regular food packaging material to extend shelf life till 30 days. Toxicity due to high amount of silver can be prevented with these composites and can be safely used in healthcare applications such as food packaging, wound dressing, hospital bed lining and surgical apparels.
Current Opinion in Biomedical Engineering, 2017
Three-dimensional bioprinting can prove to be a promising technology for bone tissue regeneration... more Three-dimensional bioprinting can prove to be a promising technology for bone tissue regeneration as it facilitates good spatio-temporal distribution of cells in scaffold. The feed for bioprinting is bioink, which comprises of cells incorporated in the scaffold material. Progress has been made on the incorporation of growth factors in the bioink, which not only enables efficient regeneration but at the same time proves the feasibility of large constructs. Important parameters which determine the suitability of bioink have been discussed here. Lack of vascularization limits the success of this technology in its present form. Advances in inducing vascularization and growth factors have also been discussed. Towards the end, challenges and opinions in the area of bioprinting of bone tissue regeneration have been presented.
Applied Surface Science, 2017
Sustained release and prevention of burst release for low half-life drugs like Diclofenac sodium ... more Sustained release and prevention of burst release for low half-life drugs like Diclofenac sodium is crucial to prevent drug related toxicity. Electrospun nanofibers have emerged recently as potential carrier materials for controlled and sustained drug release. Here, we present a facile method to prevent burst release by tuning the surface wettability through template assisted micropatterning of drug loaded electrospun cellulose acetate (CA) nanofibers. A known amount of drug (Diclofenac sodium) was first mixed with CA and then electrospun in the form of a nanofabric. This as-spun network was hydrophilic in nature. However, when electrospinning was carried out through non-conducting templates, viz nylon mesh with 50 and 100μm size openings, two kinds 2 of hydrophobic micro-patterned CA nanofabrics were produced. In vitro transdermal testing of our nanofibrous mats was carried out; these tests were able to show that it would be possible to create a patch for transdermal drug release. Further our results show that with optimized micropatterned dimensions, a zero order sustained drug release of up to 12 h may be achieved for the transdermal system when compared to non-patterned samples. This patterning caused a change in the surface wettability, to a hydrophobic surface, resulting in a controlled diffusion of the hydrophilic drug. Patterning assisted in controlling the initial burst release, which is a significant finding especially for low half-life drugs.
researchers from the Indian Institute of Technology (IIT) Hyderabad have developed a new drug del... more researchers from the Indian Institute of Technology (IIT) Hyderabad have developed a new drug delivery system to treat fungal infections, without running the risk of inducing drug resistance
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Papers by Shivakalyani Adepu