Search

Absorption enhancers are often a major component of solid oral peptide formulations as compared to the active pharmaceutical ingredient and excipients. This commonly results in poor tabletability that is hard to mitigate in direct compaction by addition of small amounts of excipients. To improve the tabletability of bulky absorption enhancers, the model absorption enhancers, sodium cholate and deoxycholic acid, were co-spray-dried with hydroxypropyl methylcellulose E5, where the percentage of absorption enhancers was not lower than 90% (w/w). The physicochemical properties of the resulting powders were assessed by laser diffraction, scanning electron microscopy, X-ray powder diffraction, thermogravimetric analysis, and differential scanning calorimetry. The powders were compressed into tablets, and the tabletability was evaluated. Co-spray drying with 10% of hydroxypropyl methylcellulose significantly improved the tabletability of the both absorption enhancers. Moreover, it was demonstrated that small particle size and amorphous state rather than high moisture content contributed to the improved tabletability of the spray-dried powders. The study suggests that spray drying technology can be promising to overcome the poor tabletability of oral peptide formulation consisting of large amounts of absorption enhancers., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Atherosclerosis is the underlying cause for cardiovascular disease. Current pharmacotherapies are limited by the inadequate targeting and insufficient treatment. Herein, inspired by the interaction of macrophage and lipoprotein as a typical hallmark of atherosclerosis, hybrid nanovesicles (MLP‐NVs) are designed by fusion of anti‐inflammatory M2‐phenotype macrophage membranes and lipidated peptide (DOPE‐pp‐HBSP) to mimic the binding manner of cell‐lipoprotein for atherosclerotic treatment. Through hybridization of M2 macrophage membranes and lipidated peptide film, MLP‐NVs facilitate the inflammatory cell internalization at atherosclerotic site, and sequester the proinflammatory cytokines to suppress local inflammation. Moreover, MLP‐NVs exhibit a matrix metalloprotease 2 (MMP2)‐responsive release of the peptide HBSP in plaques, leading to the restoration of dysfunctional endothelial cells. In the ApoE−/− mice with atherosclerosis, simvastatin‐loaded MLP‐NVs provide comprehensive treatment by inherent inflammation suppression, endothelial repair, and cholesterol efflux capacities, resulting in atherosclerotic plaques regression. Through closely mimicking physiological cues, this biomimetic hybrid nanovesicle platform provides a potential strategy for anti‐atherosclerotic therapy. [ABSTRACT FROM AUTHOR]

Mutual interference between surface ligands on multifunctional nanoparticles remains a significant obstacle to achieving optimal drug-delivery efficacy. Here, we develop ligand-switchable nanoparticles which resemble viral unique surfaces, enabling them to fully display diverse functions. The nanoparticles are modified with a pH-responsive stretchable cell-penetrating peptide (Pep) and a liver-targeting moiety (Gal) (Pep/Gal-PNPs). Once orally administered, the acidic environments trigger the extension of Pep from surface in a virus-like manner, enabling Pep/Gal-PNPs to traverse intestinal barriers efficiently. Subsequently, Gal is exposed by Pep folding at physiological pH, thereby allowing the specific targeting of Pep/Gal-PNPs to the liver. As a proof-of-concept, insulin-loaded Pep/Gal-PNPs are fabricated which exhibit effective intestinal absorption and excellent hepatic deposition of insulin. Crucially, Pep/Gal-PNPs increase hepatic glycogen production by 7.2-fold, contributing to the maintenance of glucose homeostasis for effective diabetes management. Overall, this study provides a promising approach to achieving full potential of diverse ligands on multifunctional nanoparticles. Displaying the correct surface functionality at the right time is important for efficient drug delivery. Here, the authors report on the pH-responsive, sequential presentation of cell-penetrating peptide and liver-targeting moiety designed to improve intestinal absorption and liver targeting and demonstrate this with insulin delivery in vivo. [ABSTRACT FROM AUTHOR]