Estudo do bioconjugado crotoxina/poli(n,n’-dimetilacrilamida-co-vinil pirrolidona) segundo a teoria da reptação

Abstract

Recently, our laboratories have explored the synthesis of new materials to delivery of drugs specifically to cancerous tissues, for enhanced therapeutic efficacy and reduced systemic toxicity. In this work, the synthesis of poly(N,N´-dimethylacrylamide-co-NVinyl- 2-pirrolidone) copolymers (PDMAm-co-VP) loaded with crotoxin is described. Crotoxin have interesting antitumour property and so may be used in patients with advanced cancer. Our particular interest is the reduction of the neurotoxic effects of crotoxin by their entrapment in the bioerodible PDMAm-co-VP copolymer. In this work we report the study on the diffusion of a crotoxin from PDMAm-co-VP. A mathematical model was developed to describe the release of protein from the PDMAm-co-VP polymer according to the reptation model. Using the reptation model it is shown that the diffusion process measured by the diffusion coefficient, D, is dominated by the chain length, degree of polymerization, N, and the chain architecture. By considering the reptation motion of chain ends across the interface, it has been shown that the interfacial width increases with t¼. The second stage of chrotoxin interdiffusion occurs at times greater than tr (reptation time) where the diffusion process is predicted to change to give an interfacial width that grows with a t½ dependence, recovering the classical picture of Fickian diffusion. The experimental results suggested a sort of tuning of parameters that are related to the molecular properties of the polymer, and the drug, such as the polymer molecular weight, the water and the drug diffusion coefficient, the equilibrium volume fractions of the crotoxin, and the water-polymer interaction parameter, could result in sustained zero-order release system. Our study indicated that the PDMAm-co-VP copolymers confer stability to crotoxin, causing controlled release and reduction of the toxic effects of protein.