Development of phytosterol-loaded silver nanoparticles for ameliorating haemorrhoidal complications via the AMPK pathway-a mechanistic approach.

The aim of the current study was to synthesize silver nanoparticles (PLSNPs) using green technology by means of phytosterol-enriched fractions fromBlumea laceraextracts (EAF) and evaluate their toxicological and anti-haemorrhoidal potential. The average size of the synthesized particles was found to be 85.64 nm by scanning electron microscopy and transmission electron microscopy. Energy dispersive spectroscopy showed the elemental composition of PLSNPs to be 12.59% carbon and 87.41% silver, indicating the capping of phytochemicals on the PLSNPs. The PLSNPs were also standardized for total phytosterol content using chemical methods and high-perfromance liquid chromatography. The PLSNPs were found to be safe up to 1000 mg kg-1as no toxicity was observed in the acute and sub-acute toxicity studies performed as per OECD guidelines. After the induction of haemorrhoids, experimental animals were treated with different doses of EAF, PLSNPs and a standard drug (Pilex) for 7 d, and on the eighth day the ameliorative potential was assessed by evaluating the haemorrhoidal (inflammatory severity index, recto-anal coefficient) and biochemical (tumour necrosis factor-alpha and interleukin-6) parameters and histology of the recto-anal tissue. The results showed that treatment with PLSNPs and Pilex significantly (p< 0.05) reduced haemorrhoidal and biochemical parameters. This was further supported by restoration of altered antioxidant status. Further, a marked reduction in the inflammatory zones along with minimal dilated blood vessels was observed in the histopathological study. The results of molecular docking studies also confirmed the amelioration of haemorrhoids via AMP-activated protein kinase (AMPK)-mediated reduction of inflammation and endothelin B receptor modification by PLSNPs. In conclusion, PLSNPs could be a good alternative for the management of haemorrhoids.

Third Generation Cyclodextrin Graft with Polyurethane Embedded in Hydrogel for a Sustained Drug Release: Complete Shrinkage of Melanoma.

An injectable hydrogel-based drug delivery carrier has been developed for long-term drug release by assembling various generations of cyclodextrin (CD) followed by hydrophobic layers to control the drug release for effective cancer treatment. Three generations of CD are designed through urethane linkages using small spacers to create a large hydrophilic core, which is covered with hydrophobic layers of polyurethane through grafting to maintain the hydrophilic hydrophobic balance of the whole superstructure. Drug release becomes sustained from the intricate superstructure following the non-Fickian diffusion process, resulting in massive cancer cell killing as compared to the low killing rate from the pure drug/material arising from its burst release. The superstructure is found to be a good biomaterial, and its drug-loaded conjugate as a carrier is applied to albino mice to treat their tumors, generated through a melanoma cell line. A drug-embedded superstructure is inoculated in an injectable hydrogel and is placed subcutaneously, below the tumor site, which completely healed the melanoma. No side effect was observed, as opposed to the conventional/control system, due to a sustained drug release from the superstructure as evident from histopathological studies of sensitive body organs and biochemical parameters. Thus, a new design of the vehicle heals the melanoma tumor by enhancing the bioavailability of drug and specific interaction without having any side effects as opposed to conventional chemotherapeutic treatment.