Oral peptide delivery: in-vitro evaluation of thiolated alginate/poly(acrylic acid) microparticles.
The purpose of this study was to develop an oral thiomer-based microparticulate delivery system for insulin by ionic gelation. The microparticulate matrix consisted of either poly(acrylic acid)-cysteine (PAA-Cys) and alginate-cysteine (Alg-Cys) or the corresponding unmodified polymers (PAA, Alg). Two different viscosities of alginates were provided for the study, low and medium. Three different types of microparticles were prepared via ionic gelation with calcium (Alg, AlgPAA and AlgPAA-Cys) and their different properties evaluated in-vitro (particle size and shape, drug loading and release profile, swelling and stability). The mean particle size of all formulations ranged from 400 to 600 microm, revealing the lowest for thiolated microparticles. SEM micrographs showed different morphological profiles for the three different types of microparticles. Encapsulation efficiency of insulin increased within the following rank order: Alg (15%) < AlgPAA (40%) < AlgPAA-Cys (65%). Alginate and AlgPAA microparticles displayed a burst release after 30 min, whereas the thiolated particles achieved a controlled release of insulin over 3 h. The swelling ratio was pH dependent: in simulated intestinal fluid microparticles exhibited a much higher water uptake compared with simulated gastric fluid. Due to the formation of intraparticulate disulfide bonds during the preparation process, thiolated particles revealed a higher stability. It was also observed that the viscosity of the two alginates used had no influence on the properties of the particles. According to these results AlgPAA-Cys microparticles obtained by ionic gelation and stabilized via disulfide bonds might be an alternative tool for the oral administration of therapeutic peptides.
Greimel
Alexander
A
Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 52, Josef-Möller-Haus, 6020 Innsbruck, Austria.
Werle
Martin
M
Bernkop-Schnürch
Andreas
A
D000180:Acrylic Resins / Q000737:chemistry*; D000284:Administration, Oral; D000464:Alginates / Q000737:chemistry; D002118:Calcium / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D005750:Gastric Juice / Q000378:metabolism; D005782:Gels / Q000737:chemistry; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry*; D007328:Insulin / Q000008:administration & dosage / Q000737:chemistry*; D007419:Intestinal Secretions / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D014783:Viscosity
D000180:Acrylic Resins; D000464:Alginates; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005782:Gels; D006603:Hexuronic Acids; D007004:Hypoglycemic Agents; D007328:Insulin; C006903:carbopol 940; D020723:Glucuronic Acid; D003545:Cysteine; D002118:Calcium