DOSE AND LOAD STUDIES FOR SUBCUTANEOUS AND ORAL DELIVERY OF POLY(LACTIDE-CO-GLYCOLIDE) MICROSPHERES CONTAINING OVALBUMIN

Citation
T. Uchida et al., DOSE AND LOAD STUDIES FOR SUBCUTANEOUS AND ORAL DELIVERY OF POLY(LACTIDE-CO-GLYCOLIDE) MICROSPHERES CONTAINING OVALBUMIN, Pharmaceutical research, 11(7), 1994, pp. 1009-1015
Citations number
23
Categorie Soggetti
Pharmacology & Pharmacy",Chemistry
Journal title
ISSN journal
07248741
Volume
11
Issue
7
Year of publication
1994
Pages
1009 - 1015
Database
ISI
SICI code
0724-8741(1994)11:7<1009:DALSFS>2.0.ZU;2-G
Abstract
Poly(lactide-co-glycolide) microspheres containing different loads of OVA (0.05, 0.1, 0.5 and 1.0% w/w) were manufactured by a w/o/w emulsio n/solvent evaporation method. Low load efficiencies of less than 20% w ere observed. Normal size distributions with mean volume diameters ran ging from 3.7 to 4.7 mu m were obtained for different batches. The in vitro release of OVA from different loaded microspheres showed an expe cted burst release with all batches. The in vivo dose study (1, 10, 25 , 50 mu g of OVA) was performed by subcutaneous and oral inoculation i n mice by single (0 week) or double (0 and 3 weeks) administration of PLGA 50/50 microspheres containing 0.1% OVA. Subcutaneous administrati on showed an immune response (serum Ig levels by ELISA) statistically (Fisher's paired t-test; P < 0.05) above OVA saline negative controls at 3, 6 and 12 weeks after administration. Oral administration of micr ospheres produced statistically higher systemic immune responses at th e higher doses. Single and double inoculation orally and subcutaneousl y produced similar serum antibody levels. The in vivo load study was p erformed by subcutaneous and oral administration to mice of 25 mu g OV A contained in various loaded (0.05, 0.1, 0.5 and 1.0% w/w) microspher es. Serum immune responses at 3, 6, and 12 weeks after inoculation wer e statistically above OVA saline controls and were inversely proportio nal to the OVA load using either route. This observation suggested a r elationship between the number of microspheres delivered and the in vi vo serum response. Single subcutaneous administration of 0.05 or 0.1% OVA loaded PLGA 50/50 microspheres induced larger immune responses com pared with complete Freund's adjuvant.