Indira Gandhi National Tribal University

Over the last few decades, synthetic polyesters have stimulated the interest of many researchers.Polycaprolactone (PCL) has been of particular interest in various scientific and industrial fields since the 1970s-1980s.The biodegradability, biocompatibility, physicochem. and mech. properties of this aliphatic polyester set it apart.PCL is popular and plays a major role in increasing drug bioavailability.The bioavailability of a drug is 100% when administered i.v. and the drug′s bioavailability reduces if it is delivered via other routes such as oral, due to inadequate absorption or first-pass metabolismThe role of polymer PCL nanoparticles (NPs) has been widely researched because of their biocompatibility with cells and tissue and their enhanced controlled and sustained release characteristics.PCL NPs can be synthesized using a variety of methods and these methods are divided into groups based on whether a polymerization reaction is necessary for the particles to form, or if the NPs can instead form immediately from a preformed polymer or macromol.This review examines both problems associated with drug bioavailability and different methods for improving the bioavailability of drugs that are poorly water-soluble and have low bioavailability.Addnl., it describes the role and application of PCL in enhancing drug bioavailability.

Macromolecule translocation across the plasma membrane remains a major challenge for therapeutic development. In this study, we evaluated whether macropinocytosis inducers (MPIs) increase therapeutic internalization in colorectal cancer cell (CRC) lines. We synthesized 15 novel MPI compounds (3-(((3-mercapto-5-(pyridin-4-yl)-4H-1,2,4-triazol-4-yl)imino)methyl)quinolin-2-ol (BAPT))), of which, two lead compounds, BAPT 78 (50 μM) and BAPT 54 (50 μM), significantly increased high-molecular-weight dextran and albumin uptake, in SW620 and HCT116 CRC cells by macropinocytosis, which was confirmed by the CF-488A green fluorescent probe. BAPT 78 vacuoles contained early endosomal markers and interacted with lysosomes, indicating acidic endosomes. In addition, BAPT 54 and BAPT 78 increased the uptake of anti-tubulin antibodies in SW620 and HCT116 cells. However, the plant toxin, saporin (10.9-350 nM), and small-interfering RNA (siRNA; 50 nM) delivery to SW620 cells was limited, perhaps due to low endolytic capacity of the MPI compounds. Combining BAPT 78 with the low-molecular-weight anticancer drugs, doxorubicin and paclitaxel, significantly enhanced their cytotoxicity in CRC (SW620, HCT116) and in the triple-negative breast cancer (TNBC) cell lines, SUM159 and SUM159-PAC200 (paclitaxel-resistant TNBC). Overall, this study provides proof-of-concept to deliver macromolecules and small molecule therapeutics intracellularly by activating macropinocytosis.

We present a holistic framework to evaluate groundwater contamination and its associated health risks in a mining-affected region of India with a focus on identifying key processes driving groundwater chemistry, quantifying contaminant levels, and assessing the health risks. Results revealed a complex hydrochemical regime driven by seasonal changes from pre- to post-monsoon and the intermixing of both geogenic and anthropogenic factors. A gradual change from carbonate weathering to silicate weathering from pre- to post-monsoon was observed, while anthropogenic inputs due to agricultural activities resulted in the contamination of groundwater by anions like NO₃^-. High F^- levels were found to be impacted by pH levels resulting in either the desorptive release or dissolution of F^--bearing minerals in the mining areas. Health risk assessments showed that children were the most vulnerable. Although the imprints of agricultural inputs were more explicit on the groundwater quality than that of mining activities, the monsoon-driven dilution shifts clustering patterns of all quality parameters, indicating active recharge and mixing. The study presented an examination of enhanced weathering processes occurring in hard-rock aquifers characterized by substantial recharge rates, which are adversely affected by the cumulative influence of mining operations and agricultural practices. Future research should focus on implementing long-term monitoring programs to safeguard water resources and public health in similar settings globally.