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Microencapsulation of luteinizing hormone-releasing hormone agonist in poly (lactic-co-glycolic acid) microspheres by spray drying.

07:00 EST 11th January 2020 | BioPortfolio

Summary of "Microencapsulation of luteinizing hormone-releasing hormone agonist in poly (lactic-co-glycolic acid) microspheres by spray drying."

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 kD Mw) dissolved in methylene chloride (DCM) was spray-dried before washing the microspheres in cold ddHO and freeze-drying. The spray drying microencapsulation was characterized by: particle sizes/distribution (span), morphology, drug/gelatin loading, encapsulation efficiency, and residual DCM and water content. Long-term release was tested over 9 weeks in PBS + 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, glass transition temperature (T) or hydrated T, 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 LHRHa-like leuprolide.

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This article was published in the following journal.

Name: Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
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Medical and Biotech [MESH] Definitions

A potent synthetic long-acting agonist of GONADOTROPIN-RELEASING HORMONE that regulates the synthesis and release of pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE.

Receptors with a 6-kDa protein on the surfaces of cells that secrete LUTEINIZING HORMONE or FOLLICLE STIMULATING HORMONE, usually in the adenohypophysis. LUTEINIZING HORMONE-RELEASING HORMONE binds to these receptors, is endocytosed with the receptor and, in the cell, triggers the release of LUTEINIZING HORMONE or FOLLICLE STIMULATING HORMONE by the cell. These receptors are also found in rat gonads. INHIBINS prevent the binding of GnRH to its receptors.

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A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Luteinizing hormone regulates steroid production by the interstitial cells of the TESTIS and the OVARY. The preovulatory LUTEINIZING HORMONE surge in females induces OVULATION, and subsequent LUTEINIZATION of the follicle. LUTEINIZING HORMONE consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH and FSH), but the beta subunit is unique and confers its biological specificity.

A decapeptide that stimulates the synthesis and secretion of both pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE. GnRH is produced by neurons in the septum PREOPTIC AREA of the HYPOTHALAMUS and released into the pituitary portal blood, leading to stimulation of GONADOTROPHS in the ANTERIOR PITUITARY GLAND.

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