Random amphiphilic copolymeric sub-micro particles as a carrier shielding from enzymatic attack for peptides and proteins delivery

Abstract

The development of peptide drugs and therapeutic proteins is limited by their rapid clearance in liver and other body tissues by proteolytic enzymes, and consequently peptides and proteins are difficult to administer except by injection. There is a growing effort to circumvent these problems by designing strategies to deliver these drugs to specific site of the body. Among them, this peptide carrier presents several advantages for protein therapy including stability in physiological buffer and lack of toxicity. Here, we have been developing a novel bioadhesive polymer matrix that protects entrapped proteins and peptides from degradation by serine protease. Poly(2-lactobionamidoethyl methacrylate-ran-3-acrylamidophenylboronic acid-ran-methoxypolyethylene glycol methacrylate) glycopolymers were synthesized and could self-assemble into the sub-micro particles. The loading capability of insulin, as a drug model, and the insulin release from the particles were assessed. The inhibitory effect of the particles toward trypsin, elastase, and chymotrypsin was evaluated in vitro. Insulin was effectively encapsulated, up to 10%, and could be stained release in vitro. These glycopolymers displayed a strong inhibitory effect toward these exopeptidases. Therefore, novel glycopolymers with excellent inhibitory activity against proteolytic enzymes and reasonable mucoadhesivity might be a useful tool in overcoming the enzymatic barrier to the mucosal delivery (e.g. nasal and buccal) of therapeutic peptides or proteins.

Block versus Random Amphiphilic Glycopolymer Nanopaticles as Glucose-Responsive Vehicles

“…Stimuli-responsive polymer nanoparticles have drawn increasing interests in drug delivery due to their various advantages. − These polymer nanoparticles could trigger drug release in response to local environmental conditions such as pH, temperature, light, ionic strength, magnetic field and glucose. − Among these stimuli, a most important one is glucose molecule, because insulin-dependent diabetes mellitus characterized by accumulating glucose concentrations in the blood has been a major global public health epidemic. , Moreover, the current treatment for diabetes requires persistent monitoring of blood glucose levels and multiple daily insulin injections . This injection not only impinges on the patient quality of life but also fails to precisely control the insulin dosage.…”

“…Jennifer et al developed poly­(3-acrylamidophenylboronic acid pinacol ester)- b -poly­( N , N -dimethylacrylamide) and studied the sugar- and pH-responsive behaviors . Previously, our group has established phenylboronic acid-based block glycopolymer and explored their potential as glucose-responsive vehicles in drug delivery. − Although block polymers play an important role in these copolymers, it should be noted that random copolymer with the similar polymeric configuration exhibited good stimuli-response behaviors. − Tian et al prepared amphiphilic random copolymer that showed photoresponse behavior . Chi et al displayed a novel thermo- and photoresponsive polypseudorotaxane between pillararene WP7 and an azobenzene-containing random copolymer .…”

Comparison of virus-capsid mimicking biologic-shell based versus polymeric-shell nanoparticles for enhanced oral insulin delivery

“…Aliquots of 200 µl were withdrawn at scheduled time intervals (15/30/60/120 min) and the reaction was promptly halted by adding 100 µl 0.1 N hydrochloric acid solution. After the mixture was subjected to centrifugation (14,000 rpm, 30 min), the leftover insulin content in the supernatant was determined using HPLC method [16] .…”