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Therapeutic Peptides Are Preferentially Solubilized in Specific Microenvironments within PEG-PLGA Polymer Nanoparticles

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Bibliographic Details
Title: Therapeutic Peptides Are Preferentially Solubilized in Specific Microenvironments within PEG-PLGA Polymer Nanoparticles
Authors: López-Rios de Castro, Raquel, Ziolek, Robert M, Ulmschneider, Martin B, Lorenz, Christian D
Source: López-Rios de Castro, R, Ziolek, R M, Ulmschneider, M B & Lorenz, C D 2024, 'Therapeutic Peptides Are Preferentially Solubilized in Specific Microenvironments within PEG-PLGA Polymer Nanoparticles', Nano Letters, vol. 24, no. 6, pp. 2011-2017. https://doi.org/10.1021/acs.nanolett.3c04558
Publication Year: 2024
Collection: King's College, London: Research Portal
Subject Terms: Polymers/chemistry, Lactic Acid/chemistry, Polyethylene Glycols/chemistry, Drug Delivery Systems/methods, Peptides, Nanoparticles/chemistry, Drug Carriers/chemistry, Polyesters
Description: Polymeric nanoparticles are a highly promising drug delivery formulation. However, a lack of understanding of the molecular mechanisms that underlie their drug solubilization and controlled release capabilities has hindered the efficient clinical translation of such technologies. Polyethylene glycol-poly(lactic- co-glycolic) acid (PEG-PLGA) nanoparticles have been widely studied as cancer drug delivery vehicles. In this letter, we use unbiased coarse-grained molecular dynamics simulations to model the self-assembly of a PEG-PLGA nanoparticle and its solubulization of the anticancer peptide, EEK, with good agreement with previously reported experimental structural data. We applied unsupervised machine learning techniques to quantify the conformations that polymers adopt at various locations within the nanoparticle. We find that the local microenvironments formed by the various polymer conformations promote preferential EEK solubilization within specific regions of the NP. This demonstrates that these microenvironments are key in controlling drug storage locations within nanoparticles, supporting the rational design of nanoparticles for therapeutic applications.
Document Type: article in journal/newspaper
Language: English
DOI: 10.1021/acs.nanolett.3c04558
Availability: https://kclpure.kcl.ac.uk/portal/en/publications/f4297d89-daea-49b9-bdb0-6c26e4c4e05a
https://doi.org/10.1021/acs.nanolett.3c04558
http://www.scopus.com/inward/record.url?scp=85184815917&partnerID=8YFLogxK
Rights: info:eu-repo/semantics/openAccess
Accession Number: edsbas.92FF6C5E
Database: BASE
Description
Abstract:Polymeric nanoparticles are a highly promising drug delivery formulation. However, a lack of understanding of the molecular mechanisms that underlie their drug solubilization and controlled release capabilities has hindered the efficient clinical translation of such technologies. Polyethylene glycol-poly(lactic- co-glycolic) acid (PEG-PLGA) nanoparticles have been widely studied as cancer drug delivery vehicles. In this letter, we use unbiased coarse-grained molecular dynamics simulations to model the self-assembly of a PEG-PLGA nanoparticle and its solubulization of the anticancer peptide, EEK, with good agreement with previously reported experimental structural data. We applied unsupervised machine learning techniques to quantify the conformations that polymers adopt at various locations within the nanoparticle. We find that the local microenvironments formed by the various polymer conformations promote preferential EEK solubilization within specific regions of the NP. This demonstrates that these microenvironments are key in controlling drug storage locations within nanoparticles, supporting the rational design of nanoparticles for therapeutic applications.
DOI:10.1021/acs.nanolett.3c04558