Design and Evaluation of Dissolving Microneedles for Enhanced Dermal Delivery of Propranolol Hydrochloride.

Jingjing He,Lu Li,Wei Wu,Zichen Zhang,Yi Lu,Xianzi Zheng,Jianping Qi

doi:10.3390/pharmaceutics13040579

Jingjing He, Lu Li + Show 5 more

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https://doi.org/10.3390/pharmaceutics13040579

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Journal: Pharmaceutics	Publication Date: Apr 19, 2021
Citations: 29	License type: CC BY 4.0

Affiliation: Fudan University, Pudong Medical Center

Abstract

Oral propranolol hydrochloride has been the first-line treatment for infantile hemangioma (IH), whereas systemic exposure to propranolol has the potential of causing serious adverse reactions. Dermal delivery of propranolol is preferable due to high local drug concentration and fewer adverse effects. However, propranolol hydrochloride (BCS class I) is highly hydrophilic and has difficulty in penetrating the stratum corneum (SC) barrier. Dissolving microneedles (MNs) are an efficient tool for overcoming the barrier of the SC and enhancing dermal drug delivery. In this study, propranolol hydrochloride-loaded dissolving MNs were fabricated by using hyaluronic acid and polyvinyl pyrrolidone as matrix materials. Controllable drug loading in needle tips was achieved by a two-step casting procedure. The needles were good in mechanical strength for penetrating the SC while presented excellent dissolving capability for releasing propranolol hydrochloride. In comparison with the solution counterpart, irrespective of being applied to intact skin or solid MNs-pretreated skin, dissolving MNs significantly increased the permeability and skin retention of propranolol. In conclusion, dissolving MNs could be a potential approach for enhancing dermal delivery of propranolol to treat IH.

Highlights

Dermal delivery is a preferable drug administration method for treating diseases localized within the skin due to its advantages of higher local drug concentration, lower systematic exposure, absence of hepatic first-pass metabolism, and better patient compliance [1]
Propranolol hydrochloride loaded microneedles were fabricated in this study
The matrix composed of hyaluronic acid (HA) and polyvinyl pyrrolidone (PVP)-K90 provided excellent mechanical strength for piercing the skin and dissolved quickly when absorbing interstitial fluid after insertion

Summary

Introduction

Dermal delivery is a preferable drug administration method for treating diseases localized within the skin due to its advantages of higher local drug concentration, lower systematic exposure, absence of hepatic first-pass metabolism, and better patient compliance [1]. The barrier function of the stratum corneum (SC) prevents the entry of the majority of therapeutics into the skin [2], the hydrophilic ones [3,4]. Microneedles, an array of micron-sized needles, are the most effective because they enable breaking the barrier of the stratum corneum for delivery of therapeutics into the skin [23,24]. The needles are only 0.2–1.5 mm in length, producing minimal invasion and enabling self-administration like a patch [25,26]. A myriad of physical devices and approaches, such as microneedles (MNs) [5,6,7], iontophoresis [8,9,10], sonophoresis [11,12,13], magnetophoresis [14,15,16], electroporation [17,18,19], and photomechanical wave [20,21,22], have been developed to facilitate cutaneous penetration.

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