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  • Title: The influence of polymer architecture on the protective effect of novel comb shaped amphiphilic poly(allylamine) against in vitro enzymatic degradation of insulin--towards oral insulin delivery.
    Author: Thompson CJ, Tetley L, Cheng WP.
    Journal: Int J Pharm; 2010 Jan 04; 383(1-2):216-27. PubMed ID: 19766178.
    Abstract:
    Nanocomplexes formed between amphiphilic poly(allylamine) (PAA) and insulin were prepared, characterised and the impact of polymer architecture on the protection of insulin against three enzymes was investigated. PAA previously modified with either cetyl or cholesteryl pendant groups at two levels of hydrophobic grafting and its quaternised derivatives were used to produce polymer-insulin nanocomplexes. Transmittance study, differential scanning calorimetry, hydrodynamic size and zeta potential measurement were conducted and the morphology of the complexes were visualised using transmission electron microscopy. All polymers were found to have an optimal polymer to insulin ratio of 0.4:1 mg mL(-1) with particle size ranging from 88 to 154 nm. Polymer architecture has an impact on the morphology of the complexes produced but has little influence on the complexation efficiency (CE). Almost all polymers were unable to produce complexes with a CE of above 50%. Most polymers demonstrated an ability to reduce insulin degradation by trypsin while the polymer architecture plays a pivotal role against alpha-chymotrypsin and pepsin degradation. Quaternised cholesteryl polymers were able to significantly limit insulin degradation by alpha-chymotrypsin while cetyl polymers were particularly effective against pepsin degradation. These results indicated that a combination of polymers might be required to enhance protection against all three proteolytic enzymes for efficacious oral delivery of insulin.
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