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Intracellular protein delivery and gene transfection by electroporation using a microneedle electrode array.

ABSTRACT: The impact of many biopharmaceuticals, including protein- and gene-based therapies, has been limited by the need for better methods of delivery into cells within tissues. Here, intracellular delivery of molecules and transfection with plasmid DNA by electroporation is presented using a novel microneedle electrode array designed for the targeted treatment of skin and other tissue surfaces. The microneedle array is molded out of polylactic acid. Electrodes and circuitry required for electroporation are applied to the microneedle array surface by a new metal-transfer micromolding method. The microneedle array maintains mechanical integrity after insertion into pig cadaver skin and is able to electroporate human prostate cancer cells in vitro. Quantitative measurements show that increasing electroporation pulse voltage increases uptake efficiency of calcein and bovine serum albumin, whereas increasing pulse length has lesser effects over the range studied. Uptake of molecules by up to 50% of cells and transfection of 12% of cells with a gene for green fluorescent protein is demonstrated at high cell viability. It is concluded that the microneedle electrode array is able to electroporate cells, resulting in intracellular uptake of molecules, and has potential applications to improve intracellular delivery of proteins, DNA, and other biopharmaceuticals.

SUBMITTER: Choi SO

PROVIDER: S-EPMC3516926 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Intracellular protein delivery and gene transfection by electroporation using a microneedle electrode array.

Choi Seong-O SO Kim Yeu-Chun YC Lee Jeong Woo JW Park Jung-Hwan JH Prausnitz Mark R MR Allen Mark G MG

Small (Weinheim an der Bergstrasse, Germany) 20120213 7

The impact of many biopharmaceuticals, including protein- and gene-based therapies, has been limited by the need for better methods of delivery into cells within tissues. Here, intracellular delivery of molecules and transfection with plasmid DNA by electroporation is presented using a novel microneedle electrode array designed for the targeted treatment of skin and other tissue surfaces. The microneedle array is molded out of polylactic acid. Electrodes and circuitry required for electroporatio ...[more]

PMID: 22328093

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Project description:IntroductionExisting HIV therapy using oral antiretrovirals (ARVs) can result in pill fatigue and sub-optimal adherence. Microneedle array patches (MAPs) offer non-invasive, blood-free and painless drug delivery, and may improve patient adherence. The objective of this study was to develop a novel physiologically-based pharmacokinetic (PBPK) model to simulate the systemic pharmacokinetics of cabotegravir and rilpivirine MAPs using the intradermal route.MethodsThe developed PBPK models were qualified against observed pharmacokinetic data after intramuscular (IM) and intradermal administration of long-acting nanoformulated rilpivirine to rats, and for IM administration of both drugs to healthy adults. Qualified models were then utilised to estimate suitable MAP characteristics (e.g. nanoformulation dose and release rates) and inform dosing strategies to maintain plasma concentrations above target trough concentrations for the designated dosing interval.ResultsPBPK models simulated q4-weekly loading and maintenance doses of 360 mg and 180 mg for long-acting formulated cabotegravir between the release rates of 1 × 10-3-3 × 10-3h-1 and 1 × 10-3-1.5 × 10-3h-1 respectively, for a 70 kg adult. Estimated patch size was 60 cm2 for a 360 mg dose of cabotegravir. For q4-weekly dosing, rilpivirine required a 1080 mg loading dose and a 540 mg maintenance dose with release rates of 1.5 × 10-3-2.5 × 10-3h-1 and 5 × 10-4-1 × 10-3h-1, respectively. Weekly dosing was also evaluated to assess the potential application from a smaller patch size. The ability to self-administer via a patch that is only left in place for a short duration makes longer durations less important than for some other long-acting approaches. Weekly cabotegravir required 60 mg between release rates 7 × 10-3-9 × 10-3h-1 and rilpivirine required 270 mg and 180 mg respectively between release rates of 7 × 10-3-9 × 10-3h-1.DiscussionThis model estimated optimal dose and release rates for cabotegravir and rilpivirine MAPs. Our approach provides a computational platform to support rational development of intradermal administration strategies to tackle problems associated with chronic oral ARV administration.

Dataset Information

Intracellular protein delivery and gene transfection by electroporation using a microneedle electrode array.

Publications

Intracellular protein delivery and gene transfection by electroporation using a microneedle electrode array.

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