Microneedle-based drug delivery: studies on delivery parameters and biocompatibility

Abstract

There is a significant interest in the application of microneedles in intradermal drug delivery systems. Previous studies have demonstrated that skin permeation of drugs can be increased by orders of magnitude with microneedle insertion. In this study, emphasis is placed on the development of low cost, painless intradermal microneedle systems that can enhance the percutaneous drug permeation. Microneedles of octagonal pyramidal shape with the length of 150 mum were employed, and the capabilities of skin permeation enhancement under different delivery conditions were examined. The delivery parameters taken into account included the insertion time and the area of insertion. It was found that when solid microneedle arrays of 150 mum in length were pierced into human dermatomed skin for 5 to 60 s, microconduits with the depth of 50 to 80 mum were created to facilitate the percutaneous permeation of drugs. In percutaneous tests, it was demonstrated that the permeability coefficient of calcein (MW = 622.55) was significantly increased by 10(4) to 10(5) times compared to that on intact skin. In terms of biocompatibility, biological evaluation indicated a broad spectrum of safety for the microneedle system. These results suggest that the octagonal pyramidal microneedles can be an effective tool in developing novel intradermal drug delivery system.

Sustained release of insulin through skin by intradermal microdelivery system

“…The interior layers of skin as a reservoir of drug may account for this result. It has been reported previously that the intradermal microdelivery system formed microconduits with limited depth (<100 µm) in skin (Wu et al 2008). Thus microneedles penetrated the stratum corneum and accessed the underlying viable epidermis, while leaving the dermis intact.…”

“…They are 150 µm in height, with a base length of about 100 µm, a cone angle of 38°and a needle tip less than 1 µm wide. The wafer was fixed onto the supporting column of an applicator to form an intradermal drug delivery system (Wu et al 2008), which provided an insertion force of approximately 2 N to assist the insertion in application. The applicator was provided by Suzhou Natong Nanobiotechnology Ltd. in China.…”

“…Considering the long-term treatment in insulin therapy, patient compliance of the system should be given special consideration; and such short needle length would help to improve patient compliance since it had been proved be safe and painless (Kaushik et al 2001). The microdelivery system also contained an applicator force as a compensation for short needle length, with guaranteed efficiency for skin puncturing both in vitro (Wu et al 2008) and in vivo . Pharmacodynamic properties were optimized by delivery parameters and compared with those of subcutaneously injected regular and biphasic insulin for the first time, to indicate the efficacy of intradermal microdelivery system for insulin therapy.…”

Microneedles: an emerging transdermal drug delivery system

“…Wu et al used confocal laser scanning microscopy (CLSM) to demonstrate the depth of penetration of Rhodamine B in human dermatomed skin using microneedles of 150 mm length. [46] They reported the concentration of the dye to be very weak below 80 mm depth. They also evaluated the penetration of model drug using Franz diffusion cell across the microneedle-treated and untreated skin and reported enhancement in penetration by 10 4 to 10 5 times with use of microneedles.…”

“…Reproduced with permission from Elsevier. [48] Biological safety test [46] Extraction of chemicals from microneedles was done by immersing microneedles in physiological saline at 37°C for 72 h. The extract was then directly applied on shaved intact human skin for checking dermal irritation. Negative result of the test revealed the biological safety of the microneedles.…”