Exploring the Effects of Process Parameters During W/O/W Emulsion Preparation and Supercritical Fluid Extraction on the Protein Encapsulation and Release Properties of PLGA Microspheres

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2024 Mar 28

PMID 38543196

Authors

Heejun Park

Affiliations

Soon will be listed here.

Abstract

In this study, protein-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared via supercritical fluid extraction of emulsion (SFEE) technology. To understand the correlation between process parameters and the main quality characteristics of PLGA microspheres, a comprehensive prior study on the influence of process variables on encapsulation efficiency (EE), initial drug burst release (IBR), morphology, surface property, and particle size distribution (PSD) was conducted within a wide process condition range of each unit process step, from the double-emulsion preparation step to the extraction step. Bovine serum albumin (BSA), a high-molecular weight-protein that is difficult to control the IBR and EE of PLGA microspheres with, was used as a model material. As double-emulsion manufacturing process parameters, the primary (W/O) and secondary emulsion (W/O/W) homogenization speed and secondary emulsification time were evaluated. In addition, the effect of the SFEE process parameters, including the pressure (70-160 bar), temperature (35-65 °C), stirring rate (50-1000 rpm), and flow rate of supercritical carbon dioxide, SC-CO (1-40 mL/min), on PLGA microsphere quality properties were also evaluated. An increase in the homogenization speed of the primary emulsion resulted in an increase in EE and a decrease in IBR. In contrast, increasing the secondary emulsification speed resulted in a decrease in EE and an increase in IBR along with a decrease in microsphere size. The insufficient secondary emulsification time resulted in excessive increases in particle size, and excessive durations resulted in decreased EE and increased IBR. Increasing the temperature and pressure of SFEE resulted in an overall increase in particle size, a decrease in EE, and an increase in IBR. It was observed that, at low stirring rates or SC-CO flow rates, there was an increase in particle size and SPAN value, while the EE decreased. Overall, when the EE of the prepared microspheres is low, a higher proportion of drugs is distributed on the external surface of the microspheres, resulting in a larger IBR. In conclusion, this study contributes to the scientific understanding of the influence of SFEE process variables on PLGA microspheres.

Citing Articles

Preparation and Characterization of the Release Behavior of PVA: Na-Alg Microsphere Containing Fampridine.

Akyol Ozdemir S, Yuksel Guvenilir F Turk J Pharm Sci. 2025; 21(6):557-565.

PMID: 39801108 PMC: 11730001. DOI: 10.4274/tjps.galenos.2024.61667.

The drug release of PLGA-based nanoparticles and their application in treatment of gastrointestinal cancers.

Sun R, Chen Y, Pei Y, Wang W, Zhu Z, Zheng Z Heliyon. 2024; 10(18):e38165.

PMID: 39364250 PMC: 11447355. DOI: 10.1016/j.heliyon.2024.e38165.

References

Cho M, Sah H . Formulation and process parameters affecting protein encapsulation into PLGA microspheres during ethyl acetate-based microencapsulation process. J Microencapsul. 2005; 22(1):1-12. DOI: 10.1080/02652040400026269. View

Crotts G, Park T . Protein delivery from poly(lactic-co-glycolic acid) biodegradable microspheres: release kinetics and stability issues. J Microencapsul. 1998; 15(6):699-713. DOI: 10.3109/02652049809008253. View

Muddineti O, Omri A . Current trends in PLGA based long-acting injectable products: The industry perspective. Expert Opin Drug Deliv. 2022; 19(5):559-576. DOI: 10.1080/17425247.2022.2075845. View

Wajcberg E, Tavaria A . Exenatide: clinical aspects of the first incretin-mimetic for the treatment of type 2 diabetes mellitus. Expert Opin Pharmacother. 2009; 10(1):135-42. DOI: 10.1517/14656560802611832. View

Sturesson C, Artursson P, Ghaderi R, Johansen K, Mirazimi A, Uhnoo I . Encapsulation of rotavirus into poly(lactide-co-glycolide) microspheres. J Control Release. 1999; 59(3):377-89. DOI: 10.1016/s0168-3659(99)00014-0. View

Jain R . The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials. 2000; 21(23):2475-90. DOI: 10.1016/s0142-9612(00)00115-0. View

Yang Y, Chen Q, Lin J, Cai Z, Liao G, Wang K . Recent Advance in Polymer Based Microspheric Systems for Controlled Protein and Peptide Delivery. Curr Med Chem. 2019; 26(13):2285-2296. DOI: 10.2174/0929867326666190409130207. View

McGinity , ODonnell . Preparation of microspheres by the solvent evaporation technique. Adv Drug Deliv Rev. 2000; 28(1):25-42. DOI: 10.1016/s0169-409x(97)00049-5. View

Vlachopoulos A, Karlioti G, Balla E, Daniilidis V, Kalamas T, Stefanidou M . Poly(Lactic Acid)-Based Microparticles for Drug Delivery Applications: An Overview of Recent Advances. Pharmaceutics. 2022; 14(2). PMC: 8877458. DOI: 10.3390/pharmaceutics14020359. View

10.

Yoo J, Won Y . Phenomenology of the Initial Burst Release of Drugs from PLGA Microparticles. ACS Biomater Sci Eng. 2021; 6(11):6053-6062. DOI: 10.1021/acsbiomaterials.0c01228. View

11.

Liu B, Dong Q, Wang M, Shi L, Wu Y, Yu X . Preparation, characterization, and pharmacodynamics of exenatide-loaded poly(DL-lactic-co-glycolic acid) microspheres. Chem Pharm Bull (Tokyo). 2010; 58(11):1474-9. DOI: 10.1248/cpb.58.1474. View

12.

Freitas S, Merkle H, Gander B . Microencapsulation by solvent extraction/evaporation: reviewing the state of the art of microsphere preparation process technology. J Control Release. 2005; 102(2):313-32. DOI: 10.1016/j.jconrel.2004.10.015. View

13.

Zheng C, Liang W . A one-step modified method to reduce the burst initial release from PLGA microspheres. Drug Deliv. 2010; 17(2):77-82. DOI: 10.3109/10717540903509001. View

14.

Liggins R, Burt H . Paclitaxel loaded poly(L-lactic acid) (PLLA) microspheres. II. The effect of processing parameters on microsphere morphology and drug release kinetics. Int J Pharm. 2004; 281(1-2):103-6. DOI: 10.1016/j.ijpharm.2004.05.027. View

15.

Huang Y, Tsai Y, Liu Y . Effects of solvent evaporation rate on the properties of protein-loaded PLLA and PDLLA microspheres fabricated by emulsion-solvent evaporation process. J Microencapsul. 2002; 19(4):463-71. DOI: 10.1080/02652040210140706. View

16.

Jyothi N, Prasanna P, Sakarkar S, Prabha K, Ramaiah P, Srawan G . Microencapsulation techniques, factors influencing encapsulation efficiency. J Microencapsul. 2010; 27(3):187-97. DOI: 10.3109/02652040903131301. View

17.

Ajiboye A, Trivedi V, Mitchell J . Preparation of polycaprolactone nanoparticles via supercritical carbon dioxide extraction of emulsions. Drug Deliv Transl Res. 2017; 8(6):1790-1796. PMC: 6280808. DOI: 10.1007/s13346-017-0422-3. View

18.

Li X, Zhang Z, Harris A, Yang L . Bridging the gap between fundamental research and product development of long acting injectable PLGA microspheres. Expert Opin Drug Deliv. 2022; 19(10):1247-1264. DOI: 10.1080/17425247.2022.2105317. View

19.

Zhang C, Yang L, Wan F, Bera H, Cun D, Rantanen J . Quality by design thinking in the development of long-acting injectable PLGA/PLA-based microspheres for peptide and protein drug delivery. Int J Pharm. 2020; 585:119441. DOI: 10.1016/j.ijpharm.2020.119441. View

20.

Wang L, Yang B, Du X, Yi C . Optimisation of supercritical fluid extraction of flavonoids from Pueraria lobata. Food Chem. 2015; 108(2):737-41. DOI: 10.1016/j.foodchem.2007.11.031. View