Protein micro and nanoencapsulation within glycol-chitosan/Ca2+/alginate matrix by spray drying

Department of Chemical Engineering, Queen's University, Kingston, Ontario, Canada.
Drug Development and Industrial Pharmacy (Impact Factor: 2.1). 03/2011; 37(6):619-27. DOI: 10.3109/03639045.2010.533681
Source: PubMed


Encapsulation of therapeutic peptides and proteins into polymeric micro and nanoparticulates has been proposed as a strategy to overcome limitations to oral protein administration. Particles having diameter less than 5 µm are able to be taken up by the M cells of Peyer's patches found in intestinal mucosa. Current formulation methodologies involve organic solvents and several time consuming steps. In this study, spray drying was investigated to produce protein loaded micro/nanoparticles, as it offers the potential for single step operation, producing dry active-loaded particles within the micro to nano-range. Spherical, smooth surfaced particles were produced from alginate/protein feed solutions. The effect of operational parameters on particle properties such as recovery, residual activity and particle size was studied using subtilisin as model protein. Particle recovery depended on the inlet temperature of the drying air, and mean particle size ranged from 2.2 to 4.5 µm, affected by the feed rate and the alginate concentration in the feed solution. Increase in alginate:protein ratio increased protein stability. Presence of 0.2 g trehalose/g particle increased the residual activity up to 90%. Glycol-chitosan-Ca(2+)alginate particles were produced in a single step operation, with resulting mean diameter of 3.5 μm. Particles showed fluorescein isothiocyanate labeled bovine serum albumin (BSA)-protein entrapment with increasing concentration toward the particle surface. Similar, limited release profiles of BSA, subtilisin and lysozyme were observed in gastric simulation, with ultimate full release of the proteins in gastrointestinal simulation.

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    • "Se ha logrado microcapsular péptidos y proteínas provenientes de la albúmina del suero en matrices de alginato-glicol-quitosano altamente resistentes a las condiciones gastrointestinales. La incorporación de estas microcápsulas en alimentos promete ser un suplemento proteico de usos nutricionales específicos (Erdinc y Neufeld, 2011). "

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    ABSTRACT: Context: Alginate-chitosan pellets prepared by extrusion-spheronization technique exhibited fast drug dissolution. Objective: This study aimed to design sustained-release alginate pellets through rapid in situ matrix coacervation by chitosan during dissolution. Methods: Pellets made of alginate with chitosan and/or calcium acetate were prepared using solvent-free melt pelletization technique which prevented reaction between processing materials during agglomeration and allowed such reaction to occur only in dissolution phase. Results: Drug release was retarded in pH 2.2 medium when pellets were formulated with calcium acetate or chitosan till a change in medium pH to 6.8. The sustained-release characteristics of calcium alginate pellets were attributed to pellet dispersion and rapid cross-linking by soluble Ca(2+) during dissolution. The slow drug release characteristics of alginate-chitosan pellets were attributed to polyelectrolyte complexation and pellet aggregation into swollen structures with reduced erosion. The drug release was, however, not retarded when both calcium acetate and chitosan coexisted in the same matrix as a result of chitosan shielding of Ca(2+) to initiate alginate cross-linkages and rapid in situ solvation of calcium acetate induced fast pellet dispersion and chitosan losses from matrix. Conclusion: Similar to calcium alginate pellets, alginate-chitosan pellets demonstrated sustained drug release property though via different mechanisms. Combination of alginate, chitosan and calcium acetate in the same matrix nevertheless failed to retard drug release via complementary drug release pattern.
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    ABSTRACT: Background: Spray drying has been used as a means to encapsulate therapeutics in polymeric matrices to improve stability and alter pharmacokinetics. This research aims to characterize alginate microparticles formed by spray drying to encapsulate insulin for therapeutic delivery applications. Methods: Particle size was characterized by laser diffraction spectroscopy, morphology by scanning electron microscopy, and protein and polymer distribution by confocal laser scanning microscopy. In addition, particle fines collected from the spray-dryer exhaust unit were characterized for size and morphology. The insulin encapsulation efficiency (EE) was determined after particle dissolution through quantification by spectrophotometric analysis. An in-vitro bioassay involving stimulation of rat L6 myoblasts was developed to confirm the bioactivity of released insulin. Results: Mean diameter of the product was 2.1 ± 0.3 μm. Larger particles appeared spherical, with some smaller particles presenting surface topography variability and divoting. Protein EE was 38.2% ± 9.5%, with confocal microscopy showing the protein and polymer concentrated at the surface of larger particles, but more evenly distributed throughout smaller particles. A bioassay for the in-vitro quantification of insulin bioactivity was developed by calibrating the ratio of phosphorylated to total cellular protein kinase B (PKB; also known as AKT). in insulin-stimulated rat L6 myoblasts. Insulin released from the particles was 88% ± 15% bioactive, showing that spray drying had minimal impact on protein structure. Conclusion: Spray drying was effective in producing microparticles containing bioactive insulin. Future studies will focus on the improvement of the EE and particle uniformity with the aim of developing this technology further for the encapsulation and delivery of peptide or protein-based therapeutics.
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