Polymeric lipid vesicles with pH-responsive turning on–off membrane for programed delivery of insulin in GI tract

Abstract

A kind of polymeric lipid vesicles (PLVs) with pH-responsive turning on-off membrane for programed delivery of insulin in gastrointestinal (GI) tract was developed, which was selfassembled from the grafted amphipathic polymer of N-tocopheryl-N 0 -succinyl-e-poly-L-lysine (TP/SC-g-PLL). By controlling the grafting ratio of hydrophobic alkane and ionizable carboxyl branches, the permeability of membrane was adjustable and thus allowing insulin release in a GI-pH dependent manner. The effects of grafting degree of substitution (DS) on the pHresponsive behavior of the formed vesicles were confirmed by critical aggregation concentration determination, morphology and size characterization. Their transepithelial permeability across the GI tract was proved by both confocal visualization in vitro model of Caco-2 cellular monolayer and in vivo hypoglycemic study in diabetic rats. Accordingly, the work described here indicated that the self-assembled PLVs could be a promising candidate for improving the GI delivery of hydrophilic biomacromolecule agents.

pH‐responsive polymers for drug delivery: Trends and opportunities

“…Encapsulation of a drug in the vesicles can be projected to prolong the drug's presence in systemic circulation and thus increase the target‐specific bioavailability 99 . The phagocytic absorption of drug‐loaded vesicular delivery systems reduces drug toxicity and improves bioavailability, especially for poorly soluble drugs 139 . Furthermore, the cost of therapy can be reduced using vesicular drug administration.…”

“…99 The phagocytic absorption of drug-loaded vesicular delivery systems reduces drug toxicity and improves bioavailability, especially for poorly soluble drugs. 139 Furthermore, the cost of therapy can be reduced using vesicular drug administration. pH-responsive vesicular acts as a sustained release system, delaying the removal of quickly bio-transformed drugs.…”

Advances in pH‐Sensitive Polymers for Smart Insulin Delivery

“…In addition to the pH‐sensitive polymers mentioned above, there are several other widely used polymers like polypeptides, poly(amidoamine), poly(aspartic acid), protamine, poly( l ‐lysine) (PLL), poly(γ‐glutamic acid), poly(β‐amine ester)(PEA), dextran and derivatives, polymers containing phosphoric acid derivatives, and so on, that have been used for insulin delivery. For example, Chen and co‐workers described PEA‐based microspheres developed for oral insulin delivery .…”

Glucose‐Responsive Microneedle Patch With Variable Crosslinking Density and Flexible Core–Shell Structure for Insulin Delivery

“…In this study, in order to reduce the use of glucose-responsive materials and further improve the glucose-responsive performance, we developed a crosslinking-density variable microneedle patch with a core-shell structure. ɛ-Polylysine (PLL), a relatively lowcost biodegradable poly(amino acid), is commonly used in the food industry [18] and also explored for the application of drug delivery [19] recently due to its abundant modifiable amino groups. Therefore, it is promising to provide higher safety by selecting PLL as the skeleton.…”