Human beta defensin-2 loaded PLGA nanoparticles impregnated in collagen-chitosan composite scaffold for the management of diabetic wounds.

Diabetic wound (DW) is the most devastating complication resulting in significant mortality and morbidity in diabetic patients. The standard treatment of DW care fails to address the prerequisites of treating DW owing to its multifactorial pathophysiology. Henceforth, developing a single treatment strategy to handle all the loopholes may effectively manage DW. The objective of the current study was to formulate Human beta defensin-2 (HBD-2) loaded Poly (lactic-co-glycolic acid) (PLGA) nanoparticle impregnated in collagen/chitosan (COL-CS) composite scaffolds for the accelerated healing of DW. Upon investigation, the developed biodegradable crosslinked scaffold possesses low matrix degradation, optimum porosity, and sustained drug release than the non-crosslinked scaffold. In vitro studies revealed that the HBD-2 COL-CS scaffold was biocompatible and accelerated cell migration and angiogenesis. The HBD-2 COL-CS scaffold showed significant antimicrobial activity in S. aureus, E. coli, and P. aeruginosa. The in vivo studies revealed that the HBD-2 COL-CS treated group accelerated healing compared to those in COL-CS and control groups. The ELISA results indicated a significant decrease in MMP-9, TNF-α, MPO, NAG, and NO with an increase in IL-10 in HBD-2 COL-CS treated group. The accelerated healing in HBD-2 COL-CS treated group might be due to the synergistic effects of PLGA (collagen synthesis and deposition and positive angiogenic effect), HBD-2 (anti-inflammatory, antibacterial, positive angiogenic effect, cell proliferation, and migration), COL (established wound healer and stabilizer) and CS (antibacterial, controlled drug release).

Preclinical models of diabetic wound healing: A critical review.

The treatment of diabetic wounds (DWs) is always challenging for the medical community because of its multifaceted pathophysiology. Due to practical and ethical considerations, direct studies of therapeutic interventions on human subjects are limited. Thus, it is ideal for performing studies on animals having less genetic and biological variability. An ideal DW model should progress toward reproducibility, quantifiable interpretation, therapeutic significance, and effective translation into clinical use. In the last couple of decades, various animal models were developed to examine the complex cellular and biochemical process of skin restoration in DW healing. Also, these models were used to assess the potency of developed active pharmaceutical ingredients and formulations. However, many animal models lack studying mechanisms that can appropriately restate human DW, stay a huge translational challenge. This review discusses the available animal models with their significance in DW experiments and their limitations, focusing on levels of proof of effectiveness in selecting appropriate models to restate the human DW to improve clinical outcomes. Although numerous newer entities and combinatory formulations are very well appreciated preclinically for DW management, they fail in clinical trials, which may be due to improper selection of the appropriate model. The major future challenge could be developing a model that resembles the human DW environment, can potentiate translational research in DW care.

HER2 targeted biological macromolecule modified liposomes for improved efficacy of capecitabine in breast cancer.

The present research reports the beneficial effects of surface modified chitosan and tumor-homing peptide conjugated liposomes of capecitabine (CAP) for treating breast cancer. Liposomal formulation of CAP was prepared by film hydration method using cholesterol-THP conjugate (CTHP-CAP-LPs) to achieve active targeting through HER2 receptors. CTHP-CAP-LPs significantly improved the specificity and efficacy of CAP by improving cell uptake, cytotoxicity and tumor regression in tumor bearing mice. CTHP-CAP-LPs, therefore, is a promising approach to improve the anticancer effects of CAP.

Tumor homing peptide modified liposomes of capecitabine for improved apoptotic activity and HER2 targeted therapy in breast cancer: in vitro studies.

In the present study, we have formulated a liposomal formulation of cytotoxic agent capecitabine (CAP) to overcome its bioavailability issues. Then we have surface modified CAP loaded liposomes (CAP-LPs) with a tumour homing peptide (THP-CAP-LPs) to achieve site specific delivery to breast cancer cells. We found a significant cellular internalization of THP-CAP-LPs when compared to unmodified CAP-LPs. The cytotoxic effect of CAP was also significantly improved with THP-CAP-LPs by downregulating anti-apoptotic proteins and upregulating pro-apoptotic proteins as observed by Western blot analysis. THP-CAP-LPs mediated delivery of CAP can be, therefore, a promising approach for improving antitumor activity and reducing off-target effects.