Pullulan-based dissolving microneedle arrays for enhanced transdermal delivery of small and large biomolecules

Lalitkumar K Vora,Aaron J Courtenay,Ismaiel A Tekko,Eneko Larrañeta,Ryan F Donnelly

doi:10.1016/j.ijbiomac.2019.12.184

Lalitkumar K Vora, Aaron J Courtenay + Show 3 more

Open Access

https://doi.org/10.1016/j.ijbiomac.2019.12.184

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Abstract

One specific technological advance in transdermal drug delivery is the development of dissolving microneedles (DMNs), which efficiently deliver therapeutics through a rapid dissolution of polymers after penetration into the skin. However, there is a limited range of water soluble, biodegradable polymers that can be used to manufacture DMN. Here, we report for the first time, the preparation and characterisation of a DMN system from the carbohydrate biopolymer, pullulan (PL). PL gels, of varying concentration, were studied for viscosity, film formation properties, and subsequently, microneedle formation. Model molecules and protein/peptide were loaded into PL DMN and characterised. The stability of model biomolecules, such as FITC-BSA and insulin, following DMN manufacture were assessed using circular dichroism. Ex-vivo porcine skin permeation studies using Franz diffusion cell apparatus for Flu-Na and FITC-BSA loaded PL-DMN were conducted. This study demonstrates that PL DMNs may serve as a promising tool for efficient transdermal drug delivery.

Highlights

Transdermal drug delivery systems (TDDS) are well-known within the pharmaceutical domain since the invention of nitroglycerin ointment [1]
We found that the circular dichroism (CD) spectra of PL dissolving microneedles (DMNs) loaded FITC-BSA and insulin were practically indistinguishable from that of native FITC-BSA and insulin solution (Fig. 8), indicating that the structural integrity of both proteins in PL DMN are preserved intact
The work presented here illustrates the potential of carbohydrate biopolymer PL-based DMN to deliver low and high molecular weight drug molecules across the skin

Summary

Introduction

Transdermal drug delivery systems (TDDS) are well-known within the pharmaceutical domain since the invention of nitroglycerin ointment [1]. The outermost barrier of the skin, the stratum corneum (SC), allows only lowmolecular-mass lipophilic drugs to passively penetrate the skin. This SC barrier considerably limits the transdermal delivery of larger molecules such as proteins and therapeutic genes. To increase the permeability of the SC, techniques such as ultrasound, iontophoresis, electroporation, thermal ablation and microdermabrasion have been developed. Most of these techniques have not progressed past the pre-clinical phase of testing due to the risk of skin irritation, which is unacceptable in a clinical setting [3]. Permeation enhancer and prodrug approaches have been explored extensively for TDDS with limited success [4]

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