Metformin‐loaded silver nanoparticles tailored with their in vitro, ex vivo and in silico characterization modulated via quality‐by‐design approach

Abstract Despite the substantial success of drug delivery via the transdermal route over the oral route (e.g. noninvasiveness, circumvented first‐pass metabolism), the presence of stratum corneum is the biggest hurdle and impedes resilience toward the absorption of therapeutics via transdermal routes; thus, a nanotherapeutic approach is needed for overcoming it. The current research focused on quality‐by‐design (QbD)‐based optimization of metformin (MTH) loaded silver nanoparticles (AgNPs). Polyvinyl pyrrolidone (PVPK30)‐ capped AgNPs was synthesized by a chemical reduction technique and optimized via 3 2 factorial design for the topical delivery of MTH. The developed NPs were characterized for Fourier transform infrared spectroscopy (FTIR), particle size (PS), zeta potential (ZP), polydispersity index (PDI), transmission electron microscopy (TEM), and energy‐dispersive X‐ray (EDX). The surface plasmon resonance (SPR) for AgNPs was observed at 431 nm via UV spectrophotometry due to a combined oscillation generated by free electrons of AgNPs, and was equally confirmed by EDX, resulting in elemental distribution with a specific peak (at 3.0 keV). The optimized batch of AgNPs (F0) and MTH‐loaded AgNPs (MTH‐AgNPs) (M3) revealed a PS of 161.9 and 89.98 nm, ZP of −40.2 and −33.0 mV, and PDI of 0.445 and 0.288, respectively. The drug was further subjected to its in‐silico pharmacokinetics study followed by toxicity evaluation (for MTH and AgNO 3 ). The developed hydrogel containing NPs denoted substantial drug permeability (94.53% over a period of 5 h) via goat skin mucosa. The MTH‐AgNPs‐loaded gel showed immense potential for altering skin disorders, nullifying modern‐day healthcare challenges.