IgG-loaded hyaluronan-based dissolving microneedles for intradermal protein delivery
2015
Mönkäre, Juha | Reza Nejadnik, M. | Baccouche, Khalil | Romeijn, Stefan | Jiskoot, Wim | Bouwstra, Joke A.
Dissolving microneedles are an attractive approach for non-invasive delivery of drugs via the skin, particularly when the doses are in the microgram or low-milligram range. The aim of the study was to develop hyaluronan-based, monoclonal IgG-loaded microneedles for intradermal delivery enabling efficient penetration and rapid dissolution in the skin while preserving protein stability. Microscopic analysis showed successful preparation of sharp microneedles with the tip length of ~280μm and with up to 10% (w/w) of IgG content. The water content of the microneedles was ~12% and was not affected by the protein content. The protein distribution was uniform within microneedle tips and individual arrays but some array-to-array variation of IgG level within a single preparation batch was detected. After dissolution of microneedle arrays in PBS, >80% of protein was recovered and no conformational changes were detected by fluorescence spectroscopy. At submicron level, only weak and reversible interaction between HA and IgG was found by asymmetric flow field flow fractionation analysis after the dissolution of prepared microneedles. Although, the formation of insoluble micron-size particles was detected by flow imaging microscopy the IgG amount incorporated into these particles was negligible (<5%). Finally, microneedles were able to penetrate into the epidermis of ex vivo human skin followed by the rapid dissolution of the microneedle tips in the skin. After 10min of application, the majority of the original tip length was dissolved and IgG and hyaluronan were co-deposited until a depth of 150–200μm in the skin. In conclusion, developed hyaluronan-based dissolving microneedles allow rapid non-invasive intradermal protein delivery.
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