Role of zinc in formulation of PLGA/PLA nanoparticles encapsulating betamethasone phosphate and its release profile.
The purpose of this study was to develop poly(D,L-lactic/glycolic acid) (PLGA) or poly(D,L-lactic acid) (PLA) nanoparticles of less than 200 nm in diameter that encapsulated water-soluble corticosteroid derivatives for sustained release and targeting to inflammatory sites. Nanoparticles were prepared with PLGA (or PLA), zinc, betamethasone phosphate and surfactant by an oil-in-water solvent diffusion method. With this method, the efficiency of encapsulating betamethasone phosphate in the nanoparticles and the particle size were significantly affected by various factors, such as the concentration of PLGA (or PLA) and the amount of zinc added. Nanoparticles ranging from 80 to 250 nm in diameter could be prepared, with a maximum betamethasone phosphate content of 8% (w/w). Betamethasone phosphate was gradually released from the nanoparticles in diluted serum, and the release rate depended on the glycolic/lactic acid ratio and on the molecular weight of PLGA or PLA. Betamethasone was gradually released over at least 8 days from murine macrophages that had internalized betamethasone phosphate-encapsulated nanoparticles in vitro, and the rate of release was slower than from nanoparticles prepared without zinc. These results suggest that zinc increases the efficiency of encapsulating betamethasone phosphate in nanoparticles and also promotes sustained release of betamethasone phosphate from the nanoparticles.
Ishihara
Tsutomu
T
DDS Institute, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato, Tokyo 105-8461, Japan. ishihara@jikei.ac.jp
Izumo
Nobuo
N
Higaki
Megumu
M
Shimada
Emi
E
Hagi
Tomomi
T
Mine
Lisa
L
Ogawa
Yasuaki
Y
Mizushima
Yutaka
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry; D001623:Betamethasone / Q000008:administration & dosage* / Q000737:chemistry; D002214:Capsules; D003692:Delayed-Action Preparations; D005079:Excipients; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008670:Metals / Q000737:chemistry; D051379:Mice; D010316:Particle Size; D011091:Polyesters; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
D000893:Anti-Inflammatory Agents; D002214:Capsules; D003692:Delayed-Action Preparations; D005079:Excipients; D008670:Metals; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D001623:Betamethasone; D015032:Zinc