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Preparation of Large Porous Deslorelin-PLGA Microparticles with Reduced Residual Solvent and Cellular Uptake Using a Supercritical Carbon Dioxide Process
Abstract
Purpose The purpose of this study was to prepare large-porous peptide-encapsulating polymeric particles with low residual solvent that retain deslorelin integrity, sustain drug release, and exhibit reduced epithelial and macrophage uptake. We hypothesized that supercritical carbon dioxide (SC CO2) pressure-quench treatment of microparticles prepared using conventional approach expands these particles and extracts the residual organic solvent. Methods Initial studies with crystalline L-lactide (L-PLA) and amorphous copolymers of lactide-co-glycolide (PLGA) 50:50, 65:35, and 75:25 indicated that PLGA 50:50 was the most amenable to morphological changes upon SC CO2 treatment. Therefore, we prepared deslorelin-PLGA (50:50) microparticles using the conventional emulsion-solvent evaporation method, and in a second step equilibrated with SC CO2 at various temperatures (33-37 degrees C) and pressures (1200-2000 psi) for discrete intervals followed by rapid isothermal depressurization. The particles were then characterized for morphology, polymer thermal properties, particle size, porosity, bulk density, and residual solvent content. Also, deslorelin integrity, conformation, release, and cellular uptake before and after SC CO2 treatment was determined. Results Upon SC CO2 treatment (1200 psi, 33 degrees C for 30 min), the mean particle size of the deslorelin PLGA microparticles increased from 2.2 to 13.8 microm, the mean porosity increased from 39 to 92.38% the mean pore diameter incr…
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Using supercritical CO2 as a foaming agent, organic solvents can be minimized or eliminated in the production of PLGA foams.
“Using supercritical CO2 as a foaming agent, organic solvents can be minimized or eliminated in production of PLGA foams [66].”
From Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier (2011) · cites this paper as [66]
After pressurization and rapid depressurization with CO2, thermodynamic instability leads to CO2 clustering inside the liquid polymer, and as CO2 leaves, the emulsion results in a porous polymer structure.
“After such pressurization and rapid depressurization sequence, the thermodynamic instability of CO2 molecules leads to their clustering inside the liquid polymer. As CO2 leaves, the emulsion results in a porous polymer structure [66,67].”
From Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier (2011) · cites this paper as [66]
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Metadata
- Authors
- Koushik, K., & Kompella, U. B.
- Affiliations
- University of Nebraska Medical Center (US)
- Corresponding author
- Kompella, Uday B.
- ORCID
- Kompella, Uday B.
- Venue
- Pharmaceutical Research
- Published
- 2004-03
- Volume
- 21
- Issue
- 3
- Pages
- 524-535
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- OpenAlex
- W2058464257
- Cited by
- 86
- References
- 40
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 5 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 6 · 2019: 3 · 2018: 5 · 2017: 2 · 2016: 2 · 2015: 5 · 2014: 7 · 2013: 5 · 2012: 5
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Pharmaceutical Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Nebraska Medical Center
- National Institutes of Health
- National Eye Institute (R03EY013842, EY013842)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 064172, R01DK064172)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Phase Equilibria and Thermodynamics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- deslorelin, PLGA microspheres, supercritical carbon dioxide, pressure quenching, porous particles, residual solvent removal, sustained drug release, peptide delivery, cellular uptake, beta-turn conformation, glass transition temperature, emulsion solvent evaporation, Calu-1 cells, macrophages, circular dichroism, drug release kinetics, bulk density
- MeSH terms
- Animals, Carbon Dioxide, Microscopy, Electron, Scanning, Particle Size, Polymers, Solvents, Porosity
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