PMID- 15544873 OWN - NLM STAT- MEDLINE DCOM- 20050321 LR - 20181201 IS - 0168-3659 (Print) IS - 0168-3659 (Linking) VI - 100 IP - 2 DP - 2004 Nov 24 TI - Controlled release of hyaluronan oligomers from biodegradable polymeric microparticle carriers. PG - 257-66 AB - In the present study, biodegradable microparticles of blends of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) were explored as a potential carrier for the controlled release of polysaccharide oligomers. To this end, hyaluronan (HY) oligomers of varying molecular weights were incorporated into PLGA/PEG microparticles. Using a two-level fractional factorial experimental design, four microparticle formulation parameters, the amount of PEG included in the microparticles, the initial HY loading of the microparticles, the molecular weight of HY, and the molecular weight of PLGA, were studied for their influence on the incorporation and in vitro release of HY over the period of 28 days. The entrapment efficiencies were found to range between 10+/-1% and 24+/-2% depending on the initial loading and the molecular weight of the HY oligomer used in the fabrication of the microparticles. The HY was released in a multiphasic fashion including an initial burst release, followed by two separate periods of linear release. The normalized cumulative mass released during the burst release ranged from 25.1+/-9.2% to 93.0+/-0.7% and was found to be significantly influenced by the initial HY loading, the HY molecular weight, and the PLGA molecular weight. The initial period of linear release lasted from day 1 to day 14 and displayed normalized cumulative rates of release from 0.1+/-0.0%/day to 1.4+/-0.2%/day. During this period, PEG content of the microparticles and HY molecular weight exerted the greatest influence on the rate of release. Finally, the second period of linear release lasted through the final time-point at day 28. Here, the normalized cumulative rate of release values ranged from 0.2+/-0.1%/day to 3.6+/-0.7%/day and were dependent on all formulation parameters studied. These results demonstrate the potential of PLGA/PEG blend microparticles for the controlled release of HY oligomers. FAU - Hedberg, Elizabeth L AU - Hedberg EL AD - Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77251-1892, USA. FAU - Shih, Charles K AU - Shih CK FAU - Solchaga, Luis A AU - Solchaga LA FAU - Caplan, Arnold I AU - Caplan AI FAU - Mikos, Antonios G AU - Mikos AG LA - eng GR - R01-AR48756/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - Netherlands TA - J Control Release JT - Journal of controlled release : official journal of the Controlled Release Society JID - 8607908 RN - 0 (Adjuvants, Immunologic) RN - 0 (Carbazoles) RN - 0 (Drug Carriers) RN - 0 (Excipients) RN - 0 (Polymers) RN - 0 (Solutions) RN - 0P2197HHHN (carbazole) RN - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer) RN - 26009-03-0 (Polyglycolic Acid) RN - 33X04XA5AT (Lactic Acid) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 9004-61-9 (Hyaluronic Acid) SB - IM MH - Adjuvants, Immunologic MH - Carbazoles/chemistry MH - Chemistry, Pharmaceutical MH - *Drug Carriers MH - Drug Compounding MH - Excipients MH - Hyaluronic Acid/*administration & dosage MH - Kinetics MH - Lactic Acid MH - Microspheres MH - Molecular Weight MH - Polyethylene Glycols MH - Polyglycolic Acid MH - Polylactic Acid-Polyglycolic Acid Copolymer MH - Polymers MH - Reference Standards MH - Solutions EDAT- 2004/11/17 09:00 MHDA- 2005/03/22 09:00 CRDT- 2004/11/17 09:00 PHST- 2004/03/06 00:00 [received] PHST- 2004/08/27 00:00 [accepted] PHST- 2004/11/17 09:00 [pubmed] PHST- 2005/03/22 09:00 [medline] PHST- 2004/11/17 09:00 [entrez] AID - S0168-3659(04)00401-8 [pii] AID - 10.1016/j.jconrel.2004.08.020 [doi] PST - ppublish SO - J Control Release. 2004 Nov 24;100(2):257-66. doi: 10.1016/j.jconrel.2004.08.020.