Tip-loaded fast-dissolving microneedle patches for photodynamic therapy of subcutaneous tumor

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Abstract

5-Aminolevulinic acid (ALA) based photodynamic therapy (PDT) is a modality for the treatment of cancers. However, due to its hydrophilicity and zwitterionic nature, the transdermal delivery of ALA is limited for the PDT of subcutaneous tumor. To address this problem, tip-loaded fast-dissolving microneedles made of sodium hyaluronate (HA) were fabricated by two casting method. 122 μg of ALA was loaded per microneedle patch and mainly distributed in the tips, which could improve the utilization of drug and avoid the waste of drug residue in the base of microneedle patch after use. The HA microneedles could pierce stratum corneum with insertion depth about 200 μm in isolated skin. After insertion, HA microneedles were rapidly dissolved to release the encapsulated drug to improve patients' convenience and compliance. Importantly, in a subcutaneous mouse tumor model established in BALB/c nude mice, the PDT efficacy of ALA-loaded HA microneedle group was much better than ALA injection group in spite of a relatively lower ALA dose with HA microneedles. The tumor inhibition rate of ALA-loaded HA microneedle group (containing 0.61 mg of ALA) was up to 97%, while the tumor inhibition rate of ALA injection group (containing 1.65 mg of ALA) was just 66%. In addition, microchannels created by microneedle patch were quickly recovered within 3 h after insertion. Overall, the tip-loaded fast-dissolving HA microneedle patch with ALA as drug was promising and might improve topical PDT efficacy of subcutaneous tumor in an efficient and safe manner.

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