Influence of process parameters on the protein stability encapsulated in poly-dl-lactide–poly(ethylene glycol) microspheres

234

184

One of the most challenging tasks in the delivery of therapeutic proteins from PLGAbased microparticles is the sustained and complete release of the protein in its native form.The mechanisms responsible for incomplete protein release from these devices are numerous and complex; the beneficial effect of different formulations has often been evaluated in vitro.Strategies employed for overcoming protein destabilization during the release step are reviewed in this paper. Proteins have been protected in the deleterious environment by adding stabilizers to the formulation, or by modifying the protein or the polymer. Alternatively, some strategies have aimed at avoiding the formation of the destabilizing environment. As experimental conditions may influence the results from in vitro release studies, we initially report precautions to avoid adverse effects.

Section: Use Of a More Hydrophilic Polymermentioning

confidence: 99%

How to achieve sustained and complete protein release from PLGA-based microparticles?

Giteau

Venier-Julienne

Aubert-Pouëssel

et al. 2008

234

184

“…Protein microencapsulation using this methodology reveals that the emulsification step is potentially detrimental to the biological activity of the incorporated protein (Li et al, 2000). Upon homogenisation of aqueous protein solutions with dichloromethane, for example, shear stress facilitates the formation of insoluble protein aggregates at the aqueous-organic interface of the primary emulsion (Diwan and Park, 2001).…”

Section: Introductionmentioning

confidence: 99%

Preparation and in vivo evaluation of insulin-loaded biodegradable nanoparticles prepared from diblock copolymers of PLGA and PEG

Haggag

Abdel-Wahab

Ojo

et al. 2016

A B S T R A C TThe aim of this study was to design a controlled release vehicle for insulin to preserve its stability and biological activity during fabrication and release. A modified, double emulsion, solvent evaporation, technique using homogenisation force optimised entrapment efficiency of insulin into biodegradable nanoparticles (NP) prepared from poly (DL-lactic-co-glycolic acid) (PLGA) and its PEGylated diblock copolymers. Formulation parameters (type of polymer and its concentration, stabiliser concentration and volume of internal aqueous phase) and physicochemical characteristics (size, zeta potential, encapsulation efficiency, in vitro release profiles and in vitro stability) were investigated. In vivo insulin sensitivity was tested by diet-induced type II diabetic mice. Bioactivity of insulin was studied using Swiss TO mice with streptozotocin-induced type I diabetic profile. Insulin-loaded NP were spherical and negatively charged with an average diameter of 200-400 nm. Insulin encapsulation efficiency increased significantly with increasing ratio of co-polymeric PEG. The internal aqueous phase volume had a significant impact on encapsulation efficiency, initial burst release and NP size. Optimised insulin NP formulated from 10% PEG-PLGA retained insulin integrity in vitro, insulin sensitivity in vivo and induced a sustained hypoglycaemic effect from 3 h to 6 days in type I diabetic mice..

“…However, in the development of new protein delivery methods, there are several key points that have to be considered, namely, the impact of manufacturing on the integrity of the protein (Cleland et al, 2001). During the formation of microspheres, the protein molecules are often exposed to heat, mechanic stirring, adsorption onto matrix polymer, exposure to organic solvents and surface tension, which may result in a different molecular deterioration of the protein, such as molecular breakdown, denaturation and aggregation (Li et al, 2000). Thus, a mild encapsulation method avoiding stress conditions should be selected to minimize protein denaturation and the loss of its biological activity.…”

Section: Introductionmentioning

confidence: 99%

Alginate microspheres prepared by internal gelation: Development and effect on insulin stability

Silva

Ribeiro

Figueiredo

et al. 2006

183

Recombinant human insulin was encapsulated within alginate microspheres by the emulsification/internal gelation technique with the objective of preserving protein stability during encapsulation procedure. The influence of process and formulation parameters was evaluated on the morphology and encapsulation efficiency of insulin. The in vitro release of insulin from microspheres was studied under simulated gastrointestinal conditions and the in vivo activity of protein after processing was assessed by subcutaneous administration of extracted insulin from microspheres to streptozotocin-induced diabetic rats. Microspheres mean diameter, ranging from 21 to 287 m, decreased with the internal phase ratio, emulsifier concentration, mixer rotational speed and increased with alginate concentration. Insulin encapsulation efficiency, near 75%, was not affected by emulsifier concentration, mixer rotational speed and zinc/insulin hexamer molar ratio but decreased either by increasing internal phase ratio and calcium/alginate mass ratio or by decreasing acid/calcium molar ratio and alginate concentration. A high insulin release, above 75%, was obtained at pH 1.2 and under simulated intestinal pH a complete dissolution of microspheres occurred. Extracted insulin from microspheres decreased hyperglycemia of diabetic rats proving to be bioactive and showing that encapsulation in alginate microspheres using the emulsification/internal gelation is an appropriate method for protein encapsulation.