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.

    • "Although oral lipophilic drug delivery may overcome the limitations of nasal delivery, hepatic first pass metabolism inversely affects drug bioavailability . Based on this status quo, transdermal drug delivery systems (TDDSs) are considered prospective delivery routes for lipophilic drugs as they can be used to i) easily control drug dosage [11] ii) reduce adverse reactions [12], and iii) bypass the first-pass effect [13]. Traditionally, TDDS of lipophilic drugs involved the use of topical ointments [14], gels [15] and creams [16] as well as nanocarriers such as nanoparticles [17], niosomes [18] and liposomes [19]. "
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    ABSTRACT: Lipophilic drugs are potential drug candidates during drug development. However, due to the need for hazardous organic solvents for their solubilization, these drugs often fail to reach the pharmaceutical market, and in doing so highlight the importance of solvent free systems. Although transdermal drug delivery systems (TDDSs) are considered prospective safe drug delivery routes, a system involving lipophilic drugs in solvent free or powder form has not yet been described. Here, we report, for the first time, a novel approach for the delivery of every kind of lipophilic drug in powder form based on an innovative polymeric system (IPS). The phase transition of powder form of lipophilic drugs due to interior chemical bonds between drugs and biodegradable polymers and formation of nano-sized colloidal structures allowed the fabrication of dissolving microneedles (DMNs) to generate a powerful TDDS. We showed that IPS based DMN with powder capsaicin enhances the therapeutic effect for treatment of the rheumatic arthritis in a DBA/1 mouse model compared to a solvent-based system, indicating the promising potential of this new solvent-free platform for lipophilic drug delivery.
    No preview · Article · Dec 2015 · Journal of Controlled Release
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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.
    Full-text · Article · Oct 2015 · Journal of Controlled Release
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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.
    Full-text · Article · Oct 2014 · Photodiagnosis and Photodynamic Therapy
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