Modified nanoparticles with cell-penetrating peptide and amphipathic chitosan derivative for enhanced oral colon absorption of insulin: preparation and evaluation

Abstract

(2016) Modified nanoparticles with cell-penetrating peptide and amphipathic chitosan derivative for enhanced oral colon absorption of insulin: preparation and evaluation, Drug Delivery, 23:6, 2003-2014, DOI: 10.3109/10717544.2015 AbstractColon is an ideal absorptive site for oral protein and peptide drug (insulin), and yet it poses multiple barriers against the drug absorption, such as the barriers against the drug diffusion from colon lumen toward the absorptive mucosa and permeation across colon epithelium. In this study, modified nanoparticles (Tat-CS-NPs) with cell-penetrating peptide (Tat) and amphipathic chitosan derivative (a-CS) were used as carriers to improve colonic absorption of the drug. With a-CS as emulsifier and poly(lactic-co-glycolic acid) as matrix material, Tat-CS-NPs were prepared and evaluated in vitro/vivo. Using Caco-2 cell monolayers to imitate the colonic epithelial cells, it was found that the cellular uptake amount and transcellular transportation performance of Tat-CS-NPs were much enhanced compared with those of CS-NPs and PVA-NPs. The efficacy evaluation on diabetic rat models demonstrated that the hypoglycemic effect of Tat-CS-NPs loaded with insulin was 6.89 times higher than that of PVANPs, and 1.79 times higher than that of CS-NPs. By gavage of [ 99m Tc] isotope labeled Tat-CS-NPs in mini-pigs and single-photon emission computed tomography (SPECT) on pigs' gastrointestinal tract, it was further proved that the nanoparticles could reach colon and produce pharmacological effect. In conclusion, Tat-CS-NPs as vehicles for colon-specific drug delivery may be an efficient approach to improve oral bioavailability of protein and peptide drugs.

Preparation of chitin-amphipathic anion/quaternary ammonium salt ecofriendly dressing and its effect on wound healing in mice

“…30 Therefore, it is of growing interest to study the development of amphiphilic surfaces with high resistance to biologic adhesion by combining polymers with hydrophilic antibacterial properties and materials with hydrophobic polymers or low surface energy. 12,13 Cytotoxicity was observed only on the seventh day, and group D exhibited slightly increased suppression of cell proliferation (P,0.05). This may be related to some characteristics of chitosan, chitosan quaternary ammonium salts, or amphiphilic ions.…”

“…9,11 Amphiphilic ions are hydrophilic and lipophilic, with good antipollution effect, and have been initially applied in the field of wound dressings. 12,13 Therefore, the study of chitin and quaternary ammonium salts/amphiphilic ions have become a hot field of research because of not only the wide range of potential applications and environmental protection of natural chitin sources but also the antibacterial effects of quaternary ammonium salts and the antipollution effects of amphiphilic ions. Here, we prepared a chitin-amphipathic anion/quaternary ammonium salt ecofriendly dressing and studied its antibacterial activity in vitro and effects on wound healing in mice.…”

Preparation of Chitin-graphene Eco-friendly Dressing and Its Effect on Wound Healing

“…As a natural biopolymer, chitin is widely found in the shell of lower animals, especially crustaceans, and the cell wall of lower plants, bacteria, and algae. The production of chitin is only second to cellulose in nature [1,2].…”

Intracellular delivery of messenger RNA by recombinant PP7 virus-like particles carrying low molecular weight protamine

“…They exhibit low toxicity and have the capacity to cross cellular membranes by energy-dependent and/or independent mechanisms [ 1 , 2 ]. In the process, CPPs can transport different molecules such as nanoparticles [ 3 ], liposomes [ 4 ], proteins [ 5 ], peptides [ 5 ], and oligonucleotides [ 5 – 7 ] into living cells. Different delivery strategies such as direct conjugation, co-incubation, and non-covalent or covalent cross-linking of CPPs with target molecules [ 4 – 9 ] have been investigated so far.…”