Dasatinib loaded mucoadhesive lecithin-chitosan hybrid nanoparticles for its augmented oral delivery, in-vitro efficacy and safety.

Dasatinib (DAS) is an oral tyrosine kinase inhibitor; however, its efficacy is significantly subsided by its low oral bioavailability. The present research aimed to improve DAS's oral delivery and efficacy in triple-negative breast cancer by fabricating its mucoadhesive lecithin-chitosan hybrid nanoparticles (DAS-L/CS-NPs). DAS-L/CS-NPs were optimized using Box-Behnken design which showed mean particle size and percent entrapment efficiency of 179.7 ± 5.42 nm and 64.65 ± 0.06 %, respectively. DAS-L/CS-NPs demonstrated sustained release profile in different release media up to 48 h and showed 10 times higher apparent permeability coefficient and flux than free DAS suspension. The binding of DAS-L/CS-NPs to the mucus layer was demonstrated via ex-vivo mucoadhesion study and change in absorbance using turbidimetry. In cell culture studies, DAS-L/CS-NPs revealed a 4.14-fold decrease in IC50, significantly higher cellular uptake and mitochondrial membrane depolarization, 3.82-fold increased reactive oxygen species generation and 2.10-fold enhanced apoptosis in MDA-MB-231 cells than free DAS. In in-vivo pharmacokinetic assessment, DAS-L/CS-NPs showed a 5.08-fold and 3.74-fold rise in AUC (0-t) and Cmax than free DAS suspension, respectively. An acute toxicity study revealed a good safety profile of DAS-L/CS-NPs. In a nutshell, proposed hybrid nanoparticles are promising carriers for improved oral delivery of poorly water-soluble drugs.

Core-Shell Type Lipidic and Polymeric Nanocapsules: the Transformative Multifaceted Delivery Systems.

Amongst the several nano-drug delivery systems, lipid or polymer-based core-shell nanocapsules (NCs) have garnered much attention of researchers owing to its multidisciplinary properties and wide application. NCs are structured core-shell systems in which the core is an aqueous or oily phase protecting the encapsulated drug from environmental conditions, whereas the shell can be lipidic or polymeric. The core is stabilized by surfactant/lipids/polymers, which control the release of the drug. The presence of a plethora of biocompatible lipids and polymers with the provision of amicable surface modifications makes NCs an ideal choice for precise drug delivery. In the present article, multiple lipidic and polymeric NC (LNCs and PNCs) systems are described with an emphasis on fabrication methods and characterization techniques. Far-reaching applications as a carrier or delivery system are demonstrated for oral, parenteral, nasal, and transdermal routes of administration to enhance the bioavailability of hard-to-formulate drugs and to achieve sustained and targeted delivery. This review provide in depth understanding on core-shell NC's mechanism of absorption, surface modification, size tuning, and toxicity moderation which overshadows the drawbacks of conventional approaches. Additionally, the review shines a spotlight on the current challenges associated with core-shell NCs and applications in the foreseeable future.