Electrosprayed cysteine-functionalized degradable amphiphilic block copolymer microparticles for low pH-triggered drug delivery

Marie Finnegan, Gerard Mallon, Adam Leach, Efrosyni Themistou

Research output: Contribution to journalArticle

Abstract

Thiol-functionalized polymeric microparticles have attracted interest as mucoadhesive drug delivery formulations. However, new approaches are needed to optimize the preparation of these systems for patient use. Here, N-hydroxysuccinimide (NHS)-functionalized degradable amphiphilic diblock copolymer microparticles are prepared via electrospraying and subsequently functionalized with thiols. A poly(L-lactide)-b-poly(2-(methacryloyloxy)ethyl phosphorylcholine)-st-(methacrylic acid NHS ester) (PLA-b-P(MPC-st-NHSMA)) diblock copolymer was synthesized by sequential ring opening polymerization and reversible addition–fragmentation chain transfer polymerization. One-step microparticle preparation and rhodamine B encapsulation were performed by electrospraying. Cysteine attachment to the microparticle surface via succinimide chemistry resulted in their functionalization with thiol groups. These reacted with fluorescein isothiocyanate (FITC) to provide a fluorescent tag, proving the thiol reactivity. Highly controlled release of the dye was observed at low pH over a period of 89 days. These thiol-functionalized degradable microparticles are expected to have enhanced mucoadhesive properties with high potential for use as next-generation formulations at low pH, such as gastric, drug delivery.
Original languageEnglish
Pages (from-to)5814-5820
JournalPolymer Chemistry
Volume10
Early online date16 Oct 2019
DOIs
Publication statusPublished - 14 Nov 2019

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Drug delivery
Sulfhydryl Compounds
Block copolymers
Cysteine
Ring opening polymerization
Encapsulation
rhodamine B
Pharmaceutical Preparations
Esters
Dyes
Polymerization
Acids
Gastrointestinal Agents
Drug Compounding
Phosphorylcholine
Fluorescein
Coloring Agents
N-hydroxysuccinimide

Cite this

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abstract = "Thiol-functionalized polymeric microparticles have attracted interest as mucoadhesive drug delivery formulations. However, new approaches are needed to optimize the preparation of these systems for patient use. Here, N-hydroxysuccinimide (NHS)-functionalized degradable amphiphilic diblock copolymer microparticles are prepared via electrospraying and subsequently functionalized with thiols. A poly(L-lactide)-b-poly(2-(methacryloyloxy)ethyl phosphorylcholine)-st-(methacrylic acid NHS ester) (PLA-b-P(MPC-st-NHSMA)) diblock copolymer was synthesized by sequential ring opening polymerization and reversible addition–fragmentation chain transfer polymerization. One-step microparticle preparation and rhodamine B encapsulation were performed by electrospraying. Cysteine attachment to the microparticle surface via succinimide chemistry resulted in their functionalization with thiol groups. These reacted with fluorescein isothiocyanate (FITC) to provide a fluorescent tag, proving the thiol reactivity. Highly controlled release of the dye was observed at low pH over a period of 89 days. These thiol-functionalized degradable microparticles are expected to have enhanced mucoadhesive properties with high potential for use as next-generation formulations at low pH, such as gastric, drug delivery.",
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Electrosprayed cysteine-functionalized degradable amphiphilic block copolymer microparticles for low pH-triggered drug delivery. / Finnegan, Marie; Mallon, Gerard; Leach, Adam; Themistou, Efrosyni.

In: Polymer Chemistry, Vol. 10, 14.11.2019, p. 5814-5820.

Research output: Contribution to journalArticle

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