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Uniform carboxymethyl chitosan-enveloped Pluronic F68/poly(lactic-co-glycolic acid) nano-vehicles for facilitated oral delivery of gefitinib, a poorly soluble antitumor compound.
Colloids and Surfaces. B, Biointerfaces 2019 Februrary 16
In this study, a new type of biodegradable and stable carboxymethyl chitosan (CCS)-enveloped Pluronic® F68/poly(lactic-co-glycolic acid) (PF/PLGA) nanoparticle (CCS/PF/PLGA NP) was developed, and its potential as an oral delivery vehicle to achieve pH-triggered prolonged release, enhance cellular uptake, and promote oral absorption of poorly soluble antitumor compounds was systemically studied. In this nanocarrier, a PF/PLGA NP serves as the core for effective loading, transport, and prolonged release of a chemotherapeutic agent, while a CCS surface layer acts as the shell and provides pH-responsive and mucoadhesive features. Gefitinib (GEF), an oral poorly soluble chemotherapeutic agent, was selected as the model compound. The prepared GEF-loaded CCS/PF/PLGA (GEF/CCS/PF/PLGA) NPs possessed a monodispersed spherical shape with a uniform size (242 ± 6 nm). Thermal analysis confirmed that GEF/CCS/PF/PLGA NPs were present in an amorphous form. Drug release tests showed that GEF/CCS/PF/PLGA NPs have a pH-responsive prolonged release manner with limited drug release at low gastric pH. Furthermore, the mucoadhesive property, intestinal distribution, cellular uptake, and cytotoxicity of CCS/PF/PLGA NPs were also tested. After oral administration in rats, pharmacokinetic analysis revealed that GEF/CCS/PF/PLGA NPs produced approximately 1.6-fold increased bioavailability of GEF when compared to the commercial trademarked product (Iressa® ). In addition, under accelerated stability conditions, the prepared GEF/CCS/PF/PLGA NPs exhibited excellent physicochemical stability. Our results suggest that CCS/PF/PLGA NPs exhibit great potential as an effective and stable oral delivery system for achieving pH-triggered sustained release, enhanced cellular uptake, and improved oral absorption of poorly soluble chemotherapeutic agents, such as GEF.
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