Experimental and Computational Understanding of Pulsatile Release Mechanism from Biodegradable Core-shell Microparticles

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2022 Jul 20

PMID 35857507

Authors

Morteza Sarmadi

Christina Ta

Abigail M VanLonkhuyzen

Dominique C De Fiesta

Maria Kanelli

Ilin Sadeghi

Adam M Behrens

Bailey Ingalls

Nandita Menon

John L Daristotle

Julie Yu

Robert Langer

Ana Jaklenec

Affiliations

Soon will be listed here.

Abstract

Next-generation therapeutics require advanced drug delivery platforms with precise control over morphology and release kinetics. A recently developed microfabrication technique enables fabrication of a new class of injectable microparticles with a hollow core-shell structure that displays pulsatile release kinetics, providing such capabilities. Here, we study this technology and the resulting core-shell microstructures. We demonstrated that pulsatile release is governed by a sudden increase in porosity of the polymeric matrix, leading to the formation of a porous path connecting the core to the environment. Moreover, the release kinetics within the range studied remained primarily independent of the particle geometry but highly dependent on its composition. A qualitative technique was developed to study the pattern of pH evolution in the particles. A computational model successfully modeled deformations, indicating sudden expansion of the particle before onset of release. Results of this study contribute to the understanding and design of advanced drug delivery systems.

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References

Rao R, Kumar C, Prakasham R, Hobbs P . The Taguchi methodology as a statistical tool for biotechnological applications: a critical appraisal. Biotechnol J. 2008; 3(4):510-23. DOI: 10.1002/biot.200700201. View

Ford Versypt A, Pack D, Braatz R . Mathematical modeling of drug delivery from autocatalytically degradable PLGA microspheres--a review. J Control Release. 2012; 165(1):29-37. PMC: 3518665. DOI: 10.1016/j.jconrel.2012.10.015. View

Chen W, Palazzo A, Hennink W, Kok R . Effect of Particle Size on Drug Loading and Release Kinetics of Gefitinib-Loaded PLGA Microspheres. Mol Pharm. 2016; 14(2):459-467. DOI: 10.1021/acs.molpharmaceut.6b00896. View

Ding A, Schwendeman S . Acidic microclimate pH distribution in PLGA microspheres monitored by confocal laser scanning microscopy. Pharm Res. 2008; 25(9):2041-52. PMC: 4269251. DOI: 10.1007/s11095-008-9594-3. View

Ruan G, Feng S, Li Q . Effects of material hydrophobicity on physical properties of polymeric microspheres formed by double emulsion process. J Control Release. 2002; 84(3):151-60. DOI: 10.1016/s0168-3659(02)00292-4. View

Mylonaki I, Allemann E, Delie F, Jordan O . Imaging the porous structure in the core of degrading PLGA microparticles: The effect of molecular weight. J Control Release. 2018; 286:231-239. DOI: 10.1016/j.jconrel.2018.07.044. View

Tan H, Cai Q, Agarwal S, Stephenson J, Kamat S . Impact of adherence to disease-modifying therapies on clinical and economic outcomes among patients with multiple sclerosis. Adv Ther. 2010; 28(1):51-61. DOI: 10.1007/s12325-010-0093-7. View

Zhu X, Braatz R . A mechanistic model for drug release in PLGA biodegradable stent coatings coupled with polymer degradation and erosion. J Biomed Mater Res A. 2014; 103(7):2269-79. PMC: 4454334. DOI: 10.1002/jbm.a.35357. View

Fredenberg S, Wahlgren M, Reslow M, Axelsson A . The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems--a review. Int J Pharm. 2011; 415(1-2):34-52. DOI: 10.1016/j.ijpharm.2011.05.049. View

10.

von Burkersroda F, Schedl L, Gopferich A . Why degradable polymers undergo surface erosion or bulk erosion. Biomaterials. 2002; 23(21):4221-31. DOI: 10.1016/s0142-9612(02)00170-9. View

11.

LaVan D, McGuire T, Langer R . Small-scale systems for in vivo drug delivery. Nat Biotechnol. 2003; 21(10):1184-91. DOI: 10.1038/nbt876. View

12.

Hobson J, Gummadidala P, Silverstrim B, Grier D, Bunn J, James T . Acute inflammation induced by the biopsy of mouse mammary tumors promotes the development of metastasis. Breast Cancer Res Treat. 2013; 139(2):391-401. PMC: 4038002. DOI: 10.1007/s10549-013-2575-1. View

13.

Langer R . New methods of drug delivery. Science. 1990; 249(4976):1527-33. DOI: 10.1126/science.2218494. View

14.

Washington M, Balmert S, Fedorchak M, Little S, Watkins S, Meyer T . Monomer sequence in PLGA microparticles: Effects on acidic microclimates and in vivo inflammatory response. Acta Biomater. 2017; 65:259-271. DOI: 10.1016/j.actbio.2017.10.043. View

15.

Fu K, Pack D, Klibanov A, Langer R . Visual evidence of acidic environment within degrading poly(lactic-co-glycolic acid) (PLGA) microspheres. Pharm Res. 2000; 17(1):100-6. DOI: 10.1023/a:1007582911958. View

16.

Gasmi H, Danede F, Siepmann J, Siepmann F . Does PLGA microparticle swelling control drug release? New insight based on single particle swelling studies. J Control Release. 2015; 213:120-127. DOI: 10.1016/j.jconrel.2015.06.039. View

17.

Lu X, Miao L, Gao W, Chen Z, McHugh K, Sun Y . Engineered PLGA microparticles for long-term, pulsatile release of STING agonist for cancer immunotherapy. Sci Transl Med. 2020; 12(556). PMC: 9019818. DOI: 10.1126/scitranslmed.aaz6606. View

18.

Langer R . Drug delivery and targeting. Nature. 1998; 392(6679 Suppl):5-10. View

19.

Tamada J, Langer R . Erosion kinetics of hydrolytically degradable polymers. Proc Natl Acad Sci U S A. 1993; 90(2):552-6. PMC: 45701. DOI: 10.1073/pnas.90.2.552. View

20.

Brandl F, Kastner F, Gschwind R, Blunk T, Tessmar J, Gopferich A . Hydrogel-based drug delivery systems: comparison of drug diffusivity and release kinetics. J Control Release. 2009; 142(2):221-8. DOI: 10.1016/j.jconrel.2009.10.030. View