pH-Sensitive Encapsulates of Sodium Alginate and Poly(3-Hydroxybutyrate-co-3-Hydroxyvalerate) for Dual Drug Delivery

Stimuli-responsive dual drug delivery systems (DDDS) offer potential for the co-delivery of therapeutic agents, thereby improving clinical outcomes. In this study, for the first time, we reported the development of pH-responsive nano-in-micro materials for dual-drug delivery using poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles encapsulated in pH-sensitive sodium alginate (NA) microspheres. The dual drugs, curcumin (Cur) and 5-fluorouracil (5FU), were immobilized, respectively, in nanoparticles and microspheres for the delivery of drugs as a function of pH. Various formulations with drugs, CurPNp, NAB5FU, PNpNAB5FU, CurPNpNAB, and CurPNpNAB5FU were prepared and evaluated for physicochemical properties, cell viability, and pH-dependent release. All the developed formulations were stable at physiological conditions and 70% cell viability with significant cellular uptake. pH-dependent release studies observed significant enhancement at pH 7.4 for 5FU (90%, 98%, and 97% for NAB5FU, PNpNAB5FU, and CurPNpNAB5FU, respectively) as compared to the release at pH 1.2 (58%, 64%, and 62%). Similarly, Cur release was minimal at pH 1.2 and increased at pH 7.4. The dual-drug formulation CurPNpNAB5FU exhibited optimal controlled, pH-responsive release. The developed, nontoxic DDDS can be considered for oral delivery application to treat multiple diseases through the strategic manipulation of pH-responsive polymers, NA, and PHBV.