Non-invasive Production of Multi-Compartmental Biodegradable Polymer Microneedles for Controlled Intradermal Drug Release of Labile Molecules

Transdermal drug delivery represents an appealing alternative to conventional drug administration systems. In fact, due to their high patient compliance, the development of dissolvable and biodegradable polymer microneedles has recently attracted great attention. Although stamp-based procedures guar...

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Main Authors: Mario Battisti, Raffaele Vecchione, Costantino Casale, Fabrizio A. Pennacchio, Vincenzo Lettera, Rezvan Jamaledin, Martina Profeta, Concetta Di Natale, Giorgia Imparato, Francesco Urciuolo, Paolo Antonio Netti
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-11-01
Series:Frontiers in Bioengineering and Biotechnology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fbioe.2019.00296/full
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author Mario Battisti
Raffaele Vecchione
Costantino Casale
Fabrizio A. Pennacchio
Vincenzo Lettera
Rezvan Jamaledin
Martina Profeta
Concetta Di Natale
Giorgia Imparato
Francesco Urciuolo
Francesco Urciuolo
Paolo Antonio Netti
Paolo Antonio Netti
Paolo Antonio Netti
author_facet Mario Battisti
Raffaele Vecchione
Costantino Casale
Fabrizio A. Pennacchio
Vincenzo Lettera
Rezvan Jamaledin
Martina Profeta
Concetta Di Natale
Giorgia Imparato
Francesco Urciuolo
Francesco Urciuolo
Paolo Antonio Netti
Paolo Antonio Netti
Paolo Antonio Netti
author_sort Mario Battisti
collection DOAJ
description Transdermal drug delivery represents an appealing alternative to conventional drug administration systems. In fact, due to their high patient compliance, the development of dissolvable and biodegradable polymer microneedles has recently attracted great attention. Although stamp-based procedures guarantee high tip resolution and reproducibility, they have long processing times, low levels of system engineering, are a source of possible contaminants, and thermo-sensitive drugs cannot be used in conjunction with them. In this work, a novel stamp-based microneedle fabrication method is proposed. It provides a rapid room-temperature production of multi-compartmental biodegradable polymeric microneedles for controlled intradermal drug release. Solvent casting was carried out for only a few minutes and produced a short dissolvable tip made of polyvinylpyrrolidone (PVP). The rest of the stamp was then filled with degradable poly(lactide-co-glycolide) (PLGA) microparticles (μPs) quickly compacted with a vapor-assisted plasticization. The outcome was an array of microneedles with tunable release. The ability of the resulting microneedles to indent was assessed using pig cadaver skin. Controlled intradermal delivery was demonstrated by loading both the tip and the body of the microneedles with model therapeutics; POXA1b laccase from Pleurotus ostreatus is a commercial enzyme used for the whitening of skin spots. The action and indentation of the enzyme-loaded microneedle action were assessed in an in vitro skin model and this highlighted their ability to control the kinetic release of the encapsulated compound.
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spelling doaj.art-b70c0937842443f9a9470861b7caf3772022-12-22T00:38:45ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852019-11-01710.3389/fbioe.2019.00296482506Non-invasive Production of Multi-Compartmental Biodegradable Polymer Microneedles for Controlled Intradermal Drug Release of Labile MoleculesMario Battisti0Raffaele Vecchione1Costantino Casale2Fabrizio A. Pennacchio3Vincenzo Lettera4Rezvan Jamaledin5Martina Profeta6Concetta Di Natale7Giorgia Imparato8Francesco Urciuolo9Francesco Urciuolo10Paolo Antonio Netti11Paolo Antonio Netti12Paolo Antonio Netti13Center for Advanced Biomaterials for Health Care (CABHC), Istituto Italiano di Tecnologia, Naples, ItalyCenter for Advanced Biomaterials for Health Care (CABHC), Istituto Italiano di Tecnologia, Naples, ItalyInterdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, Naples, ItalyCenter for Advanced Biomaterials for Health Care (CABHC), Istituto Italiano di Tecnologia, Naples, ItalyBiopox Srl, Naples, ItalyCenter for Advanced Biomaterials for Health Care (CABHC), Istituto Italiano di Tecnologia, Naples, ItalyCenter for Advanced Biomaterials for Health Care (CABHC), Istituto Italiano di Tecnologia, Naples, ItalyCenter for Advanced Biomaterials for Health Care (CABHC), Istituto Italiano di Tecnologia, Naples, ItalyCenter for Advanced Biomaterials for Health Care (CABHC), Istituto Italiano di Tecnologia, Naples, ItalyInterdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, Naples, ItalyDepartment of Chemical Materials and Industrial Production (DICMAPI), University of Naples Federico II, Naples, ItalyCenter for Advanced Biomaterials for Health Care (CABHC), Istituto Italiano di Tecnologia, Naples, ItalyInterdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, Naples, ItalyDepartment of Chemical Materials and Industrial Production (DICMAPI), University of Naples Federico II, Naples, ItalyTransdermal drug delivery represents an appealing alternative to conventional drug administration systems. In fact, due to their high patient compliance, the development of dissolvable and biodegradable polymer microneedles has recently attracted great attention. Although stamp-based procedures guarantee high tip resolution and reproducibility, they have long processing times, low levels of system engineering, are a source of possible contaminants, and thermo-sensitive drugs cannot be used in conjunction with them. In this work, a novel stamp-based microneedle fabrication method is proposed. It provides a rapid room-temperature production of multi-compartmental biodegradable polymeric microneedles for controlled intradermal drug release. Solvent casting was carried out for only a few minutes and produced a short dissolvable tip made of polyvinylpyrrolidone (PVP). The rest of the stamp was then filled with degradable poly(lactide-co-glycolide) (PLGA) microparticles (μPs) quickly compacted with a vapor-assisted plasticization. The outcome was an array of microneedles with tunable release. The ability of the resulting microneedles to indent was assessed using pig cadaver skin. Controlled intradermal delivery was demonstrated by loading both the tip and the body of the microneedles with model therapeutics; POXA1b laccase from Pleurotus ostreatus is a commercial enzyme used for the whitening of skin spots. The action and indentation of the enzyme-loaded microneedle action were assessed in an in vitro skin model and this highlighted their ability to control the kinetic release of the encapsulated compound.https://www.frontiersin.org/article/10.3389/fbioe.2019.00296/fullpolymer microneedlesmulti-compartmentalenzymecontrolled releaseskin model
spellingShingle Mario Battisti
Raffaele Vecchione
Costantino Casale
Fabrizio A. Pennacchio
Vincenzo Lettera
Rezvan Jamaledin
Martina Profeta
Concetta Di Natale
Giorgia Imparato
Francesco Urciuolo
Francesco Urciuolo
Paolo Antonio Netti
Paolo Antonio Netti
Paolo Antonio Netti
Non-invasive Production of Multi-Compartmental Biodegradable Polymer Microneedles for Controlled Intradermal Drug Release of Labile Molecules
Frontiers in Bioengineering and Biotechnology
polymer microneedles
multi-compartmental
enzyme
controlled release
skin model
title Non-invasive Production of Multi-Compartmental Biodegradable Polymer Microneedles for Controlled Intradermal Drug Release of Labile Molecules
title_full Non-invasive Production of Multi-Compartmental Biodegradable Polymer Microneedles for Controlled Intradermal Drug Release of Labile Molecules
title_fullStr Non-invasive Production of Multi-Compartmental Biodegradable Polymer Microneedles for Controlled Intradermal Drug Release of Labile Molecules
title_full_unstemmed Non-invasive Production of Multi-Compartmental Biodegradable Polymer Microneedles for Controlled Intradermal Drug Release of Labile Molecules
title_short Non-invasive Production of Multi-Compartmental Biodegradable Polymer Microneedles for Controlled Intradermal Drug Release of Labile Molecules
title_sort non invasive production of multi compartmental biodegradable polymer microneedles for controlled intradermal drug release of labile molecules
topic polymer microneedles
multi-compartmental
enzyme
controlled release
skin model
url https://www.frontiersin.org/article/10.3389/fbioe.2019.00296/full
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