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OACS provided excellent ability of drug loading, increasing solubility and enhanced absorption for GA, which indicated that OACS micelles as an oral drug delivery carrier may have potential research and application values.

Herein, we describe the preparation of a targeted cellular delivery system for morin hydrate (MH), based on a low-molecular-weight hyaluronic acid-poly(butyl cyanoacrylate) (HA-PBCA) block copolymer. In order to enhance the therapeutic effect of MH, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was mixed with HA-PBCA during the preparation process. The MH-loaded HA-PBCA “plain” nanoparticle (MH-PNs) and HA-PBCA/TPGS “mixed” nanoparticles (MH-MNs) were concomitantly characterized in terms of loading efficiency, particle size, zeta potential, critical aggregation concentration, and morphology. The obtained MH-PNs and MH-MNs exhibited a spherical morphology with a negative zeta potential and a particle size less than 200 nm, favorable for drug targeting. Remarkably, the addition of TPGS resulted in about 1.6-fold increase in drug-loading. The in vitro cell viability experiment revealed that MH-MNs enhanced the cytotoxicity of MH in A549 cells compared with MH solution and MH-PNs. Furthermore, blank MNs containing TPGS exhibited selective cytotoxic effects against cancer cells without diminishing the viability of normal cells. In addition, the cellular uptake study indicated that MNs resulted in 2.28-fold higher cellular uptake than that of PNs, in A549 cells. The CD44 receptor competitive inhibition and the internalization pathway studies suggested that the internalization mechanism of the nanoparticles was mediated mainly by the CD44 receptors through a clathrin-dependent endocytic pathway. More importantly, MH-MNs exhibited a higher in vivo antitumor potency and induced more tumor cell apoptosis than did MH-PNs, following intravenous administration to S180 tumor-bearing mice. Overall, the results imply that the developed nanoparticles are promising vehicles for the targeted delivery of lipophilic anticancer drugs.

N-octyl-N-Arginine chitosan (OACS) was synthesized in an attempt to combine the permeation enhancing effects of arginine-rich peptides and the drug loading capacity of the amphipathic polymers for insulin oral delivery. OACS self-assembled micelles of insulin were prepared by the conventional stirring technique, which were characterized by Dynamic light scattering, transmission electron microscopy and differential scanning calorimetry. Molecular docking by Discovery studio software confirmed that the interactions between OACS and insulin were mostly electrostatic in nature. In vitro, the result of the degradation experiment by enzyme showed that the OACS has a relative protective effect for insulin from proteolyses. Compared to the insulin solution, OACS micelles increased the Caco-2 cell's internalization by up to 22.3 folds. In vivo, the pharmacological activity PA% of series OACS-insulin micelles ranged from 7.7%-16.8%. Meanwhile by increasing arginine degree of the substitution both the uptake in Caco-2 cells and the hypoglycemic effect in diabetic rats were enhanced. Therefore, it is concluded that using arginine polymeric micelles for the enhancement of oral insulin delivery is a promising approach for the oral peptide delivery.

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