Abstract
Cancer cells can have multiple mechanisms for drug resistance that can result in decreasing the intracellular levels of drugs. Our work describes the successful development and loading of Doxorubicin (DOX) and Piperine (PIP), a P-gp inhibitor, into Lecithin/Chitosan Nanoparticles (L/CS-NPs) using a 3-factor 4-level full factorial design (Box-Behnken Design®, BBD). Optimum amounts of Lecithin (factor-A), CS (factor-B), and DOX (factor-C) were estimated to be 100, 25, and 5 mg, respectively while considering the constraints of reducing the particle size (response-R1), increasing the surface charge (R2), encapsulation (R3), and cumulative drug release (R4). Predicted coefficient of determinations (r2) for responses (R1, R2, R3 and R4) were in a reasonable agreement with the adjusted r2. Fully optimized NPs had a particle size 157.67 nm, zeta-potential of +28.14 mV, encapsulation and loading (45.96%, 8.93% for DOX and 52.91%, 8.46% for PIP), and cumulative release of 62.14% and 53.54% for DOX and PIP, respectively. Fitting of in-vitro drug release data into kinetic equations suggested the release of drugs followed Korsmeyer-Peppas model and diffusion exponent (n-value), indicated Fickian-diffusion mechanism. Our design and optimization approach has proven successful in formulating L/CS-NPs that could be an encouraging carrier for simultaneous delivery of DOX and PIP against DOX-resistant cancer cells.
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