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Cutaneous Microenvironment Responsive Microneedle Patch for Rapid Gene Release to Treat Subdermal Tumor

Cutaneous Microenvironment Responsive Microneedle Patch for Rapid Gene Release to Treat Subdermal Tumor

Xinfang Li, Qinan Xu, Peng Zhang, Xiao Zhao, Youxiang Wang

J Control Release. 2019 Nov 28;314:72-80.

PMID: 31629710

Abstract:

Transdermal gene therapy is a useful treatment for many skin lesions. By penetrating stratum corneum directly, microneedle patch (MNP) has been widely investigated to improve transdermal gene delivery. However, considering the operability and patience compliance, quick gene release was required after insertion. In this research, by utilizing acidic cutaneous environment, pH-responsive polyelectrolyte multilayers (PEM) were coated on the surface of polycaprolactone (PCL) microneedles by layer-by-layer assembly to realize rapid gene release. Dimethylmaleic anhydride-modified polylysine (PLL-DMA), a charge reversible polymer, was introduced to PEM. The PEM composed of two parts: the transition layers of (PLL-DMA/polyethyleneimine)12 and the gene-loaded layers of (p53 expression plasmid/polyethyleneimine)16. Microneedle patch modified with such PEM was marked as tr-MNP. In following experiment, Hoechst 33258 dyed model DNA was used to track modification process, fluorescent intensity of tr-MNP was obviously strengthened while the number of bilayers increased and the morphology could be maintained. Each tr-MNP could load 31μg model DNA and improve gene release. To prove this character, MNP without transition layers (ntr-MNP) was fabricated as control. Tr-MNP could release 33% of model DNA in simulative cutaneous environment (phosphate buffer saline; pH=5.5) while ntr-MNP could only release 4%. That was because PLL-DMA could achieve charge reversal in acidic cutaneous environment, leading to the collapse of transition layers and promoted the gene release. In vivo experiment showed tumor inhibit efficacy of tr-MNP treated mice could reach 90.1% while that of ntr-MNP treated mice and intravenous administration mice was only 46.4% and 30.5%. Overall, the pH-responsive gene loaded MNP could treat subcutaneous tumor efficiently and showed potential to be a platform to load many biomacromolecule.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP24980414-A	Dyed Polycaprolactone		24980-41-4	Price

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