Phospholipid coated poly(lactic acid) microspheres for the delivery of LHRH analogues

Abstract

AbstractThe aim of this work was to develop alternative peptide‐loaded microspheres using liposphere formulation—a lipid based microdispersion system. This formulation represents a new type of lipid or polymer‐based encapsulation system developed for parenteral and topical drug delivery of bioactive compounds. Our strategy was to utilize the liposphere formulation to improve the entrapment efficiency and release profile of triptorelin and leuprolide [luteinizing hormone–releasing hormone (LHRH) analogues] in vitro. Peptides (2% w/w) were loaded into lipospheres contained of polylactic acid (PLA) or poly(lactic‐co‐glycolic acid) (PLGA) with several types of phospholipids. The effects of polymer and phospholipid type and concentration, method of preparation and solvents on the liposphere characteristics, particle size, surface and bulk structure, drug diffusion rate, and erosion rate of the polymeric matrix were studied. The use of L‐PLA (Mw = 2000) and hydrogenated soybean phosphatidylcholine (HSPC) with phospholipid–polymer ratio of 1 : 6 w/w, was the most efficient composition that formed lipospheres of particle size in the range of 10 µm with most of the phospholipid embedded on the particles surface. In a typical procedure, peptides were dissolved in N‐methyl‐2‐pyrrolidone (NMP), and dispersed in a solution of polymer and phospholipids in a mixture of NMP and chloroform with the use of 0.1% poly(vinyl alcohol) (PVA) as the emulsified aqueous medium. Uniform microspheres were prepared after solution was mixed at 2000 rpm at room temperature for 30 min. Using this formulation, the entrapment efficiency of LHRH analogues in lipospheres was up to 80%, and the peptides were released for more than 30 days. Copyright © 2002 John Wiley & Sons, Ltd.