Hyaluronic acid functionalization improves dermal targeting of polymeric nanoparticles for management of burn wounds: In vitro, ex vivo and in vivo evaluations.

Owing to its intricate pathophysiology, impaired wound healing is one of the substantial challenges in the treatment of burn wounds (BWs). Despite the variety of conventional therapies available, morbidities associated with BWs have not subsided. Therefore, aim of the present study was to design an advanced nanotechnology-composited therapy for effectual management of BWs. Hyaluronic acid (HA)-functionalized curcumin (CUR) and quercetin (QUE) co-loaded nanoparticle (HA-CUR-QUE-CSNPs) were fabricated, optimized, characterized and evaluated for successful co-encapsulation of drugs, morphology, stability, drug release, cell proliferation, penetration across the skin, localization in the epidermis and dermis, and in vivo wound healing efficacy. Fabricated HA-functionalized CSNPs exhibited ultra-small size (177 ± 11 nm), good zeta potential (+37.0 ± 3.2 mV), high encapsulation efficiency (EE) (QUE ∼84% and CUR ∼64%) and loading capacity (LC) (QUE ∼38% and CUR ∼43%), and spherical shape with uniformly rough surface. HA-functionalized CSNPs showed a triphasic release pattern with Fickian diffusion kinetics, a time-mannered progression in MC3T3-E1 cells proliferation, improved penetration of CUR (2414 µg/cm2) and QUE (1984 µg/cm2) through stratum corneum, and good localization of drugs in the epidermis and dermis. A superior wound healing efficacy (98% wound closure rate at day 28) with marked histological signs of minimal infiltration of inflammatory cells, re-epithelization, ECM formation, fibroblast infiltration at wound site, granulation tissue formation, angiogenesis, and collagen deposition were also evidenced. This study concludes that HA-functionalization of polymeric NPs could be a promising approach to maximize skin penetration efficiency, localization of drugs in skin tissues, tissue regeneration and BWs healing.

Rising horizon in circumventing multidrug resistance in chemotherapy with nanotechnology.

Multidrug resistance (MDR) is one of the key barriers in chemotherapy, leading to the generation of insensitive cancer cells towards administered therapy. Genetic and epigenetic alterations of the cells are the consequences of MDR, resulted in drug resistivity, which reflects in impaired delivery of cytotoxic agents to the cancer site. Nanotechnology-based nanocarriers have shown immense shreds of evidence in overcoming these problems, where these promising tools handle desired dosage load of hydrophobic chemotherapeutics to facilitate designing of safe, controlled and effective delivery to specifically at tumor microenvironment. Therefore, encapsulating drugs within the nano-architecture have shown to enhance solubility, bioavailability, drug targeting, where co-administered P-gp inhibitors have additionally combat against developed MDR. Moreover, recent advancement in the stimuli-sensitive delivery of nanocarriers facilitates a tumor-targeted release of the chemotherapeutics to reduce the associated toxicities of chemotherapeutic agents in normal cells. The present article is focused on MDR development strategies in the cancer cell and different nanocarrier-based approaches in circumventing this hurdle to establish an effective therapy against deadliest cancer disease.