title: Stability study of full-length antibody (anti-TNF alpha) loaded PLGA microspheres.
abstract: Antibodies (Abs) require the development of stable formulations and specific delivery strategies given their susceptibility to a variety of physical and chemical degradation pathways. In this study, the encapsulation of an antibody into polylactide-co-glycolide (PLGA) based microspheres was explored to obtain a controlled-release of the incorporated drug. In order to avoid stability issues, a solid-in-oil-in-water (s/o/w) method was preferred. The solid phase was made of anti-TNF alpha monoclonal antibody (MAb) spray-dried microparticles, and the PLGA microspheres were produced using two different polymers (i.e., Resomer(®) RG505 and Resomer(®) RG755S). The stability of the MAb incorporated into the microspheres was investigated under three conditions (5 ± 3°C, 25 ± 2°C/60% RH and 40 ± 2°C/75% RH) for 12 weeks. During this stability study, it was demonstrated that the MAb loaded PLGA microspheres were stable when stored at 5 ± 3°C and that the Resomer(®) RG755S, composed of 75%(w/w) lactic acid as PLGA, was preferred to preserve the stability of the system. Storage at temperatures higher than 5°C led to antibody stability issues such as aggregation, fragmentation and loss of activity. The release profiles were also altered. Physical ageing of the system associated with changes in the glass transition temperature and enthalpy of relaxation was noticed during the storage of the MAb loaded PLGA microspheres.
authors.affiliation: Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles (ULB), Campus de la Plaine, CP 207, Boulevard du Triomphe, Brussels 1050, Belgium; Laboratory UCB Pharma S.A., Chemin du Foriest, Braine-L'Alleud 1420, Belgium. Electronic address: sarah.marquette@ucb.com.
authors.forename: S
authors.initials: S
authors.lastname: Marquette
authors.affiliation: Laboratory UCB Pharma S.A., Chemin du Foriest, Braine-L'Alleud 1420, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Peerboom
authors.affiliation: Laboratory UCB Pharma S.A., Chemin du Foriest, Braine-L'Alleud 1420, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Yates
authors.affiliation: Laboratory UCB Pharma S.A., Chemin du Foriest, Braine-L'Alleud 1420, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Denis
authors.affiliation: IRIBHM, Université Libre de Bruxelles (ULB), Campus Erasme, CP602, Route de Lennik 808, Bruxelles 1070, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Langer
authors.affiliation: Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles (ULB), Campus de la Plaine, CP 207, Boulevard du Triomphe, Brussels 1050, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Amighi
authors.affiliation: Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles (ULB), Campus de la Plaine, CP 207, Boulevard du Triomphe, Brussels 1050, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Goole
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000737:chemistry*; D045744:Cell Line, Tumor; D004355:Drug Stability; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D008863:Microspheres; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D011091:Polyesters; D014409:Tumor Necrosis Factor-alpha; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Antibody; Encapsulation; Microspheres; PLGA; Stability