In previous studies, insulin-loaded poly(alkylcyanoacrylate) nanocapsules were found to reduce the blood glucose level after oral administration to diabetic rats and dogs. The reduction of the glycemia induced by the nanocapsules was the same regardless of the insulin doses administered, but the effect appeared only after a delay of a few days. The purpose of this study was to investigate the mechanism of insulin encapsulation and the type of interactions that may exist between the polymer forming the nanocapsule wall and the insulin. The results of this study showed, based on the interfacial polymerization of isobutylcyanoacrylate, that the insulin molecule is not chemically modified during the nanoencapsulation process. In addition, no interaction between the poly(isobutylcyanoacrylate) and the insulin could be observed. The observed high encapsulation efficiency of intact insulin may be explained by the fact that the ethanol used in the preparation of the nanocapsules is responsible for the initiation of the interfacial polymerization of isobutylcyanoacrylate instead of the insulin. The zeta potential measurements suggest that insulin is located within the core of the nanocapsules. Thus the biological activity of the nanoencapsulated peptide and the high efficiency of insulin encapsulation achieved with this nanoencapsulation process cannot be explained by a specific interaction of the insulin with the polymer forming the nanocapsule's wall. It may be due, however, to the fact that the encapsulated insulin molecule is chemically intact and located within the oily core of the nanocapsules.
Progesterone-loaded microspheres are fabricated by a solvent evaporation process from a poly(D,L-lactide-co-glycolide) (85/15 PLG) and from alpha-progesterone. Methylene chloride is used as solvent and polyvinyl alcohol and methylcellulose are used as surfactants. The microspheres are characterized by scanning electron microscopy, differential scanning calorimetry, and x-ray powder diagrams. Our study shows that the morphology and the thermal behavior of PLG microspheres can vary significantly with progesterone loading and sample thermal history. Below and at 16.5% loading the microspheres exhibit a smooth outer surface. Above 23% loading, the surface becomes rough, embedded by copolymer particles or well-defined crystals. Pores and cracks can also be observed. Below 35% the progesterone is molecularly dispersed. At 35% and above crystal domains of the steroid appear and two crystalline forms are found: alpha- and beta-progesterone. The physical state of progesterone and the nature of its crystal domains dispersed in the PLG matrix can change during storage. Also a progressive development of an endothermic peak at the Tg event of the copolymer is observed during storage. No well defined relationship of peak size to progesterone loading can be shown.
Adsorption of chemically radiolabeled [14C] collagen from binary mixtures with albumin or fibrinogen was studied on the solution/air and solution/polyethylene interfaces and revealed the preferential adsorption of albumin. This phenomenon is confirmed by the data of surface tension measurements of single protein, collagen-albumin, and collagen-fibrinogen solutions. Desorption experiments clearly show that more irreversibly adsorbed collagen was found on polyethylene surfaces when adsorption was performed from collagen-fibrinogen than from collagen-albumin solutions. The combined adsorption-desorption and the surface tension data show that competitive adsorption of collagen at the hydrophobic surfaces is strongly influenced by the surface tension properties of the proteins in solution.
Collagen was isolated from rat tail tendons and acetylated with 1-14C acetic anhydride. In situ adsorption of this collagen from a buffer solution (pH = 2.7) was measured at the interfaces to air, polyethylene and polyethylene grafted with poly(maleic acid), respectively. The kinetics of adsorption were recorded for all surfaces studied and the corresponding diffusion coefficients for collagen in solution with various protein concentrations were calculated. The desorption of collagen from polymer surfaces was also studied. These experiments reveal the existence of both a reversibly and an irreversibly adsorbed collagen layer on the polymers tested. The desorption/adsorption ratio for the polyethylene is higher than that for the grafted polyethylene indicating stronger interactions of collagen with the grafted surface than with the non-modified polyethylene.
Abstract:In previous studies, insulin-loaded poly(alkylcyanoacrylate) nanocapsules were found to reduce the blood glucose level after oral administration to diabetic rats and dogs. The reduction of the glycemia induced by the nanocapsules was the same regardless of the insulin doses administered, but the effect appeared only after a delay of a few days. The purpose of this study was to investigate the mechanism of insulin encapsulation and the type of interactions that may exist between the polymer forming the nanocapsule wall and the insulin. The results of this study showed, based on the interfacial polymerization of isobutylcyanoacrylate, that the insulin molecule is not chemically modified during the nanoencapsulation process. In addition, no interaction between the poly(isobutylcyanoacrylate) and the insulin could be observed. The observed high encapsulation efficiency of intact insulin may be explained by the fact that the ethanol used in the preparation of the nanocapsules is responsible for the initiation of the interfacial polymerization of isobutylcyanoacrylate instead of the insulin. The zeta potential measurements suggest that insulin is located within the core of the nanocapsules. Thus the biological activity of the nanoencapsulated peptide and the high efficiency of insulin encapsulation achieved with this nanoencapsulation process cannot be explained by a specific interaction of the insulin with the polymer forming the nanocapsule's wall. It may be due, however, to the fact that the encapsulated insulin molecule is chemically intact and located within the oily core of the nanocapsules.
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