Controlled Drug Delivery Systems: Current Status and Future Directions.

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 the drug. It also discusses the conventional drug delivery systems and their limitations. Further, controlled drug delivery systems are discussed in detail with the design considerations, classifications and drawings. In addition, nano-drug delivery, targeted and smart drug delivery using stimuli-responsive and intelligent biomaterials is discussed with recent key findings. The paper concludes with the challenges faced and future directions in controlled drug delivery.

Heparin-Tagged PLA-PEG Copolymer-Encapsulated Biochanin A-Loaded (Mg/Al) LDH Nanoparticles Recommended for Non-Thrombogenic and Anti-Proliferative Stent Coating.

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 nanoparticles are coated. The formulation was characterized by FTIR, XRD, DSC, DLS, and TEM. In vitro drug release studies, protein adhesion, wettability, hemocompatibility, and degradation studies were performed. The drug release was modeled by mathematical models to further emphasize the mechanism of drug release. The developed drug-eluting stent coating is non-thrombogenic, and it offers close to zero-order release for 40 days, with complete polymer degradation in 14 weeks.

Ex-situ modification of bacterial cellulose for immediate and sustained drug release with insights into release mechanism.

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.