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Efficient aqueous remote loading of peptides in poly(lactic-co-glycolic acid)

Poly(lactic-co-glycolic acid) (PLGA) long-acting release depots are effective for extending the duration of action of peptide drugs. We describe efficient organic-solvent-free remote encapsulation based on the capacity of common uncapped PLGA to bind and absorb into the polymer phase net positively...

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Autores principales: Giles, Morgan B., Hong, Justin K. Y., Liu, Yayuan, Tang, Jie, Li, Tinghui, Beig, Avital, Schwendeman, Anna, Schwendeman, Steven P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9177552/
https://www.ncbi.nlm.nih.gov/pubmed/35676271
http://dx.doi.org/10.1038/s41467-022-30813-7
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author Giles, Morgan B.
Hong, Justin K. Y.
Liu, Yayuan
Tang, Jie
Li, Tinghui
Beig, Avital
Schwendeman, Anna
Schwendeman, Steven P.
author_facet Giles, Morgan B.
Hong, Justin K. Y.
Liu, Yayuan
Tang, Jie
Li, Tinghui
Beig, Avital
Schwendeman, Anna
Schwendeman, Steven P.
author_sort Giles, Morgan B.
collection PubMed
description Poly(lactic-co-glycolic acid) (PLGA) long-acting release depots are effective for extending the duration of action of peptide drugs. We describe efficient organic-solvent-free remote encapsulation based on the capacity of common uncapped PLGA to bind and absorb into the polymer phase net positively charged peptides from aqueous solution after short exposure at modest temperature. Leuprolide encapsulated by this approach in low-molecular-weight PLGA 75/25 microspheres slowly and continuously released peptide for over 56 days in vitro and suppressed testosterone production in rats in an equivalent manner as the 1-month Lupron Depot®. The technique is generalizable to encapsulate a number of net cationic peptides of various size, including octreotide, with competitive loading and encapsulation efficiencies to traditional methods. In certain cases, in vitro and in vivo performance of remote-loaded PLGA microspheres exceeded that relative to marketed products. Remote absorption encapsulation further removes the need for a critical organic solvent removal step after encapsulation, allowing for simple and cost-effective sterilization of the drug-free microspheres before encapsulation of the peptide.
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spelling pubmed-91775522022-06-10 Efficient aqueous remote loading of peptides in poly(lactic-co-glycolic acid) Giles, Morgan B. Hong, Justin K. Y. Liu, Yayuan Tang, Jie Li, Tinghui Beig, Avital Schwendeman, Anna Schwendeman, Steven P. Nat Commun Article Poly(lactic-co-glycolic acid) (PLGA) long-acting release depots are effective for extending the duration of action of peptide drugs. We describe efficient organic-solvent-free remote encapsulation based on the capacity of common uncapped PLGA to bind and absorb into the polymer phase net positively charged peptides from aqueous solution after short exposure at modest temperature. Leuprolide encapsulated by this approach in low-molecular-weight PLGA 75/25 microspheres slowly and continuously released peptide for over 56 days in vitro and suppressed testosterone production in rats in an equivalent manner as the 1-month Lupron Depot®. The technique is generalizable to encapsulate a number of net cationic peptides of various size, including octreotide, with competitive loading and encapsulation efficiencies to traditional methods. In certain cases, in vitro and in vivo performance of remote-loaded PLGA microspheres exceeded that relative to marketed products. Remote absorption encapsulation further removes the need for a critical organic solvent removal step after encapsulation, allowing for simple and cost-effective sterilization of the drug-free microspheres before encapsulation of the peptide. Nature Publishing Group UK 2022-06-08 /pmc/articles/PMC9177552/ /pubmed/35676271 http://dx.doi.org/10.1038/s41467-022-30813-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Giles, Morgan B.
Hong, Justin K. Y.
Liu, Yayuan
Tang, Jie
Li, Tinghui
Beig, Avital
Schwendeman, Anna
Schwendeman, Steven P.
Efficient aqueous remote loading of peptides in poly(lactic-co-glycolic acid)
title Efficient aqueous remote loading of peptides in poly(lactic-co-glycolic acid)
title_full Efficient aqueous remote loading of peptides in poly(lactic-co-glycolic acid)
title_fullStr Efficient aqueous remote loading of peptides in poly(lactic-co-glycolic acid)
title_full_unstemmed Efficient aqueous remote loading of peptides in poly(lactic-co-glycolic acid)
title_short Efficient aqueous remote loading of peptides in poly(lactic-co-glycolic acid)
title_sort efficient aqueous remote loading of peptides in poly(lactic-co-glycolic acid)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9177552/
https://www.ncbi.nlm.nih.gov/pubmed/35676271
http://dx.doi.org/10.1038/s41467-022-30813-7
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