Polymer Microneedles for Controlled-Release Drug Delivery

Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
Pharmaceutical Research (Impact Factor: 3.42). 05/2006; 23(5):1008-19. DOI: 10.1007/s11095-006-0028-9
Source: PubMed


As an alternative to hypodermic injection or implantation of controlled-release systems, this study designed and evaluated biodegradable polymer microneedles that encapsulate drug for controlled release in skin and are suitable for self-administration by patients.
Arrays of microneedles were fabricated out of poly-lactide-co-glycolide using a mold-based technique to encapsulate model drugs--calcein and bovine serum albumin (BSA)--either as a single encapsulation within the needle matrix or as a double encapsulation, by first encapsulating the drug within carboxymethylcellulose or poly-L: -lactide microparticles and then encapsulating drug-loaded microparticles within needles.
By measuring failure force over a range of conditions, poly-lactide-co-glycolide microneedles were shown to exhibit sufficient mechanical strength to insert into human skin. Microneedles were also shown to encapsulate drug at mass fractions up to 10% and to release encapsulated compounds within human cadaver skin. In vitro release of calcein and BSA from three different encapsulation formulations was measured over time and was shown to be controlled by the encapsulation method to achieve release kinetics ranging from hours to months. Release was modeled using the Higuchi equation with good agreement (r2 > or = 0.90). After microneedle fabrication at elevated temperature, up to 90% of encapsulated BSA remained in its native state, as determined by measuring effects on primary, secondary, and tertiary protein structure.
Biodegradable polymer microneedles can encapsulate drug to provide controlled-release delivery in skin for hours to months.

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    • "During the preparation of microneedles a wide range of stresses applied on proteins including heating, drying, complex formation with excipients and interfacial effects. For example, it has been shown that elevated temperatures can considerably compromise protein stability during the microneedle preparation [21] [22] and have to be avoided. The detrimental effects of drying and storage were shown recently with influenza hemagglutinin whose activity was reduced without optimization of the formulation [23]. "
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    ABSTRACT: 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 ∼280 μm 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 proteinwas 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 insolublemicron-size particles was detected by flowimaging 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 10 min of application, the majority of the original tip length was dissolved and IgG and hyaluronan were co-deposited until a depth of 150-200 μm in the skin. In conclusion, developed hyaluronan-based dissolving microneedles allow rapid noninvasive intradermal protein delivery.
    Journal of Controlled Release 10/2015; 218. DOI:10.1016/j.jconrel.2015.10.002 · 7.71 Impact Factor
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    • "Of note, is the fact that incorporating drug into the microneedle matrix can reduce microneedle strength. This limits the total drug loading possible, as at higher concentrations the microneedles may no longer possess sufficient mechanical strength to pierce the resilient skin barrier [39]. An in vitro study by Donnelly et al. [9] using preformed photosensitiser-loaded nanoparticles composed of poly-lactide-co-glycolic acid incorporated into soluble microneedle arrays demonstrated successful intradermal delivery of a preformed photosensitiser, but lack of transdermal delivery. "
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    ABSTRACT: Photodynamic therapy can be used in the treatment of pre-malignant and malignant diseases. It offers advantages over other therapies currently used in the treatment of skin lesions including avoidance of damage to surrounding tissue and minimal or no scarring. Unfortunately, systemic delivery of photosensitising agents can result in adverse effects, such as prolonged cutaneous photosensitivity; while topical administration lacks efficacy in the clearance of deeper skin lesions and those with a thick overlying keratotic layer. Therefore, enhancement of conventional photosensitiser delivery is desired. However, the physicochemical properties of photosensitising agents, such as extreme hydrophilicity or lipophilicity and large molecular weights make this challenging. This paper reviews the potential of microneedles as a viable method to overcome these delivery-limiting physicochemical characteristics and discusses the current benefits and limitations of solid, dissolving and hydrogel-forming microneedles. Clinical studies in which microneedles have successfully improved photodynamic therapy are also discussed, along with benefits which microneedles offer, such as precise photosensitiser localisation, painless application and reduction in waiting times between photosensitiser administration and irradiation highlighted.
    Photodiagnosis and Photodynamic Therapy 10/2014; 11(4). DOI:10.1016/j.pdpdt.2014.09.003 · 2.01 Impact Factor
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    • "There are several kinds of MNs, namely, solid MNs for skin pretreatment to increase skin permeability, MNs coated with drugs, hollow MNs for drug infusion into the skin, polymeric or polysaccharide MNs that encapsulate drugs and partially or fully dissolve in the skin [14] [15] [16] [17]. Solid MNs, which do not contain drugs themselves, enhance the permeability of drugs, for instance, small molecules, proteins and nanoparticles, by creating pores into the skins [18]. "
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    ABSTRACT: Stratum corneum is the main obstacle for drugs to pass through the skin. Microneedles are composed of arrays of micro-projections formed with different materials, generally ranging from 25–2000 μm in height. Microneedles straightly pierce the skin with its short needle arrays to overcome this barrier. Microneedles can be divided into several categories, for instance, solid microneedles, coated microneedles, and hollow microneedles and so on. However, all these types have their weak points related to corresponding mechanisms. In recent years, pioneering scientists have been working on these issues and some possible solutions have been investigated. This article will focus on the microneedle arrays consisting of hydrogels. Hydrogels are commonly used in drug delivery field. Hydrogel microneedles can be further divided into dissolving and degradable microneedles and phase transition microneedles. The former leaves drug with matrix in the skin. The latter has the feature that drugs in the matrix are delivered while the remaining ingredients can be easily removed from the skin after usage. For drugs which are required to be used every day, the phase transition microneedles are more acceptable. This article is written in order to summarize the advantages of these designs and summarize issues to be solved which may hinder the development of this technology.
    Nano-Micro Letters 07/2014; 6(3). DOI:10.5101/nml140021r · 1.98 Impact Factor
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