Effect of various additives and polymers on lysozyme release from PLGA microspheres prepared by an s/o/w emulsion technique.
Incomplete protein release from PLGA-based microspheres due to protein interactions with the polymer is one of the main issues in the development of PLGA protein-loaded microspheres. In this study, a two-dimensional adsorption model was designed to rapidly assess the anti-adsorption effect of formulation components (additives, additives blended with the polymer or modified polymers). Lysozyme was chosen as a model protein because of its strong, non-specific adsorption on the PLGA surface. This study showed that PEGs, poloxamer 188 and BSA totally inhibited protein adsorption onto the PLGA37.5/25 layer. Similarly, it was emphasised that more hydrophilic polymers were less prone to protein adsorption. The correlation between this model and the in vitro release profile was made by microencapsulating lysozyme with a low loading in the presence of these excipients by a non-denaturing s/o/w encapsulation technique. The precipitation of lysozyme with the amphiphilic poloxamer 188 prior to encapsulation exhibited continuous release of active lysozyme over 3 weeks without any burst effect. To promote lysozyme release in the latter stage of release, a PLGA-PEG-PLGA tribloc copolymer was used; lysozyme was continuously released over 45 days in a biologically active form.
INSERM, Université d'Angers, Angers, France.
A
A
Paillard-Giteau
V T
VT
Tran
O
O
Thomas
X
X
Garric
J
J
Coudane
S
S
Marchal
I
I
Chourpa
J P
JP
Benoît
C N
CN
Montero-Menei
M C
MC
Venier-Julienne
D000327:Adsorption; D000818:Animals; D002417:Cattle; D011232:Chemical Precipitation; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D009113:Muramidase / Q000008:administration & dosage* / Q000737:chemistry; D020442:Poloxamer / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013997:Time Factors
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004655:Emulsions; D005079:Excipients; D011108:Polymers; D020442:Poloxamer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D012710:Serum Albumin, Bovine; D019344:Lactic Acid; D011092:Polyethylene Glycols; D009113:Muramidase