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Microencapsulation of luteinizing hormone-releasing hormone agonist in poly (lactic-co-glycolic acid) microspheres by spray-drying
作者:Shi NQ, Zhou J, Walker J, Li L, Hong JKY, Olsen KF, Tang J, Ackermann R, Wang Y, Qin B, Schwendeman
關(guān)鍵字:Long term controlled release; Luteinizing hormone-releasing hormone agonist (LHRHa); Microencapsulation; Poly(lactic-co-glycolic acid) microspheres; Spray-drying; Thermodynamics and heat/mass transfer.
論文來(lái)源:期刊
具體來(lái)源:J Control Release. 2020 May 10;321:756-772.
發(fā)表時(shí)間:2021年
A spray drying technique was developed to prepare injectable and biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres encapsulating a model luteinizing hormone-releasing hormone agonist (LHRHa)-based peptide, leuprolide. Various spray drying parameters were evaluated to prepare 1-month controlled release formulations with a similar composition to the commercial Lupron Depot® (LD). A single water-in-oil emulsion of aqueous leuprolide/gelatin solution in PLGA 75/25 acid capped (13 kDa Mw) dissolved in methylene chloride (DCM) was spray-dried before washing the microspheres in cold ddH2O and freeze-drying. The spray-drying microencapsulation was characterized by: particle size/distribution (span), morphology, drug/gelatin loading, encapsulation efficiency, and residual DCM and water content. Long-term release was tested over 9 weeks in PBS + 0.02% Tween 80 + 0.02% sodium azide pH 7.4 (PBST) at 37 °C. Several physical-chemical parameters were monitored simultaneously for selected formulations, including: water uptake, mass loss, dry and hydrated glass transition temperature, to help understand the related long-term release profiles and explore the underlying controlled-release mechanisms. Compared with the commercial LD microspheres, some of the in-house spray-dried microspheres presented highly similar or even improved long-term release profiles, providing viable long-acting release (LAR) alternatives to the LD. The in vitro release mechanism of the peptide was shown to be controlled either by kinetics of polymer mass loss or by a second process, hypothesized to involve peptide desorption from the polymer. These data indicate spray drying can be optimized to prepare commercially relevant PLGA microsphere formulations for delivery of peptides, including the LHRHa, leuprolide.
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