title: Ultrasonic atomization and subsequent polymer desolvation for peptide and protein microencapsulation into biodegradable polyesters.
abstract: Peptide and protein microencapsulation into poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) microspheres continues to represent a technological challenge in terms of product sterility and up-scaling. The primary objective of this study was to examine the feasibility of a novel method for peptide and protein entrapment into PLA and PLGA microspheres, particularly suitable for up-scaling and aseptic processing. The method involves ultrasonic atomization of an organic polymer solution combined with subsequent organic solvent extraction by a hardening agent. The study evaluated the critical atomization conditions, the required molecular cohesion parameters of polymer solvents and hardening agent for particle preparation as well as the quality of entrapment and release as a function of polymer and peptide/protein type. Suitable polymer solvents and hardening agents were restricted to defined domains of fractional cohesion parameters: f(p) = 0.2-0.35 and f(h) = 0.2-0.4 for the polymer solvents, and f(p) = 0-0.1 and f(h) = 0-0.25 for the hardening agents. Microsphere size (0.1-100 micro m) was largely controlled by the viscosity of the atomized solution. Microencapsulation of the freely water-soluble bovine serum albumin and tetrapeptide thymocartin yielded modest efficiencies of 12-35%, whereas the slightly water-soluble octapeptide vapreotide pamoate was entrapped with 63-93% efficiency. Drug release was mainly governed by the polymer type, lasting over 100 days for BSA entrapped in PLA microspheres and; 20 days for vapreotide pamoate in PLGA 50 : 50 and for thymocartin in PLA. Very importantly, the novel method was readily accommodated within a laminar air-flow cabinet. Under aseptic conditions, sterile microspheres could be prepared. In conclusion, the novel method described may have potential in industrial environments.
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zurich, Switzerland.
authors.forename: Ch B
authors.initials: ChB
authors.lastname: Felder
authors.forename: M J
authors.initials: MJ
authors.lastname: Blanco-Príeto
authors.forename: J
authors.initials: J
authors.lastname: Heizmann
authors.forename: H P
authors.initials: HP
authors.lastname: Merkle
authors.forename: B
authors.initials: B
authors.lastname: Gander
mesh_terms: D001672:Biocompatible Materials; D001673:Biodegradation, Environmental; D004337:Drug Carriers; D004339:Drug Compounding / Q000379:methods*; D019344:Lactic Acid; D008863:Microspheres; D010316:Particle Size; D010446:Peptide Fragments; D010455:Peptides; D011091:Polyesters; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011506:Proteins; D012710:Serum Albumin, Bovine; D012995:Solubility; D012996:Solutions; D012997:Solvents; D013004:Somatostatin / Q000031:analogs & derivatives*; D013946:Thymopoietins; D014465:Ultrasonics; D014783:Viscosity
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D010446:Peptide Fragments; D010455:Peptides; D011091:Polyesters; D011108:Polymers; D011506:Proteins; D012996:Solutions; D012997:Solvents; D013946:Thymopoietins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D012710:Serum Albumin, Bovine; C051458:vapreotide; D019344:Lactic Acid; C033616:poly(lactide); D013004:Somatostatin; C045802:thymocartin