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Although paclitaxel is a front-line chemotherapeutic agent for the treatment of metastatic breast cancer, its intravenous therapy produces deleterious adverse effects. In an attempt to address the issue, the present study aimed to develop a paclitaxel loaded thermosensitive/thermoresponsive hydrogel (PTXNp-TGel) for loco-regional administration to breast tumors to provide dose-dense chemotherapy. Poloxamer and xanthan gum were used to prepare TGel by the cold method. In vitro and in vivo performance of PTXNp-TGel was compared with TGel, pure drug loaded TGel (PTX-TGel) and marketed formulation, Taxol®. The formulated PTXNp-TGel showed acceptable gelation temperature and time (37 °C and 57 s), lower viscosity at room temperature and higher viscosity at body temperature to support sol-gel transition with increasing temperature, and sustained drug release up to 21 days. Additionally, PTXNp-TGel showed negligible hemolytic toxicity as compared to PTX-TGel and Taxol®. Intratumoral administration of PTXNp-TGel produced significantly higher antitumor activity as indicated by lowest relative tumor volume (1.50) and relative antitumor proliferation rate (27.71 %) in comparison with PTX-TGel, Taxol®, and PTXNp (p 0.05). Finally, insignificant body weight loss during the experimental period, lack of hematotoxicity, nephrotoxicity, and hepatotoxicity imply improved therapeutic performance of the locally administrated dose-dense therapy of PTXNp-TGel as compared to Taxol®.

A smart linker is a crucial element throughout the creation of polymer-drug conjugates. It binds different portions or subunits altogether and may be freed by a suitable trigger, resulting in localized drug distribution and enhanced bioavailability. PEG (Polyethylene Glycol) linkers can be synthesized chemically by specifically adding functionalized groups with chemical reactivity at certain structural ends of PEG. Because they may integrate a diverse range of groups, PEG linkers are frequently utilized in molecular biology experiments due to increased water solubility, excellent biocompatibility, and non-immunogenicity. In present work, we have included various linkers which are incorporated in design of PDC’s (polymer drug conjugates) of pegylated NSAIDs (nonsteroidal anti-inflammatory drugs) through PEGylation. The main focus was to investigate the pharmacodynamic changes brought about by these linker’s conjugated to model drug Ibuprofen (IB1-IB7). The tools used for the analysis are Argus Lab 4.0 for molecular docking and pkCMS as ADMET prediction tool. The outcome of this work was, establishment of a method for choosing suitable linker for designing PDC’s for various NSAIDs and other bioactive agents.

Multi-drug resistance has shown to be one of the leading threats faced currently in many chemotherapeutic agents. Permeability glycoprotein (P-gp) is an efflux transporter in membrane, an integral part of ATP-binding cassette (ABC) transporters widely distributed in the body for cellular uptake. It is present enormously in cancerous cells and is in charge of generating transporter mediated resistance to treatments of tumorous cells in addition to blocking the entry of chemotherapeutic drugs into the cell. Natural P-gp inhibitors are derived from natural plant sources possessing basic structures like alkaloids, flavonoids, phenolics, terpenoids, saponins, sapogenins, sterols, coumarins and miscellaneous structures acting on P-gp substrate for inhibition of multi-drug resistance via inhibiting the efflux pump. They do not depict their action on the healthy cells and thus it is proven to be more effective and less toxic than synthetic P-gp inhibitor leading to enhancement in bioavailability of chemotherapeutic drugs. The significant objective of the present review is surfing through the impact of natural P-gp inhibitors having basic structures derived from the plant sources and how it inhibits the resistance of chemotherapeutic drugs together with how well it delivers chemotherapy medicines.

Reaction optimization has been a tedious task for the research chemist for very long and many approaches has been employed to achieve the best reaction condition resulting in highest yield. As an answer to this problem the statistical optimization approach has better chances of providing most acceptable solution to it. Through, our present work we have found that among other statistical approaches the custom design approach is the best methodology to be adopted for optimizing any synthetic reaction. The oxidative transformation of polyethylene glycol into polyethylene carboxylate by the use of TEMPO, NaClO and KBr; has been optimized by identifying the key factors affecting the yield and exact ratios of them to achieve highest possible yield. Here, we have employed custom design approach to further limit the experimental runs and yet find a better possible combination of reagents and conditions to get highest yield with maximum purity. This method has reduced the number of runs to only 16, which was 1024 in case of the traditional OVAT approach and in full factorial approach it was 64 runs. Thus, custom design method of DoE has been satisfactorily utilized for optimizing the oxidative derivatization of polyethylene glycol to polyethylene carboxylate.

Abstract: Autoimmune disease is increasing widely, and the biologicals in autoimmune disease play a vital role in the cure. Biologicals have an affinity to bind the specific target molecule and suppress inflammation. The different biologicals are used to treat various autoimmune diseases by preventing the cytokines from unlocking cells and causing inflammation. Each biologic targets a different cytokine. The common classes of biologic that are used to treat autoimmune disease are i) Tumor Necrosis Factor-alpha (TNFα) inhibitors and ii) Interleukin Inhibitors (IL). Along with biologics, nanomedicine has shown to be a successful method for creating customized nanomaterials with the potential to deliver medicinal agents to particular organs or tissues drugs without causing immunosuppressive or immunostimulatory adverse effects. This article reviews biologics used in treating Autoimmune Disease (AD) and the mechanism involved. The examination of current developments that have been made to create innovative nanoparticle-based therapies for autoimmune illnesses and their inclusion in vaccines. Also, recent clinical trials display nanosystem strategies for treating AD.

Development of a biodegradable nanoplatform poly(lactic-co-glycolic acid) (PLGA) for co-delivery of two drugs is hugely imperative and beneficial in anticancer therapeutics. In this study, co-deliv...

Development of a biodegradable nanoplatform poly(lactic