Hybrid membranes based on poly(vinyl alcohol) (PVA) of widely different molecular weights and ex situ nanosilica were synthesized and characterized as transdermal delivery device for Diltiazem hydrochloride. Investigations showed that change in PVA molecular weight strongly influenced physico-mechanicals of the hybrids especially at low nanosilica content than at higher levels. As for example at 1 wt %, low molecular weight PVA induced finer dispersion of silica nanoparticles resulting into higher dry state crystallinity and mechanical strength but slightly lower biocompatibility as compared to high molecular weight PVA. Those variations in physico-mechanicals finally affected Diltiazem retention and its elution from those membranes under physiological conditions. Low molecular weight PVA produced highest drug retention as well as slowest yet steady release than both high molecular weight PVA and neat PVA membranes. © 2013 Wiley Periodicals, Inc.