Jaspreet Singh Kochhar

Effect of Microneedle Geometry and Supporting Substrate on Microneedle Array Penetration into Skin

Microneedles are being fast recognized as a useful alternative to injections in delivering drugs, vaccines, and cosmetics transdermally. Owing to skins inherent elastic properties, microneedles require an optimal geometry for skin penetration. In vitro studies, using rat skin to characterize microneedle penetration in vivo, require substrates with suitable mechanical properties to mimic human skins subcutaneous tissues. We tested the effect of these two parameters on microneedle penetration. Geometry in terms of center-to-center spacing of needles was investigated for its effect on skin penetration, when placed on substrates of different hardness. Both hard (clay) and soft (polydimethylsiloxane, PDMS) substrates underneath rat skin and full-thickness pig skin were used as animal models and human skins were used as references. It was observed that there was an increase in percentage penetration with an increase in needle spacing. Microneedle penetration with PDMS as a support under stretched rat skin correlated better with that on full-thickness human skin, while penetration observed was higher when clay was used as a substrate. We showed optimal geometries for efficient penetration together with recommendation for a substrate that could better mimic the mechanical properties of human subcutaneous tissues, when using microneedles fabricated from poly(ethylene glycol)-based materials.

A simple method of microneedle array fabrication for transdermal drug delivery

Abstract The outermost layer of skin, stratum corneum, being lipophilic limits the passive transport of hydrophilic and large molecular weight drugs. Microfabrication technology has been adapted to fabricate micron scale needles, which are minimally invasive, yet able to deliver the drugs across this barrier layer. In this study, we fabricated microneedles from a biocompatible polymer, namely, poly (ethylene glycol) diacrylate. A simple lithographical approach was developed for microneedle array fabrication. Several factors including polymerization time, ultraviolet light intensity and distance from light source were studied for their effects on microneedle formation. The microneedle length and tip diameter can be controlled by varying these factors. The microneedles were shown to be able to penetrate cadaver pig skin. Model drug rhodamine B was encapsulated in the range of 50 µg to 450 µg per microneedle array. The fabricated microneedles containing rhodamine B increased the permeability by four times than the control. Altogether, we demonstrated that the microneedle arrays can be fabricated through a simple single-step process and needles were mechanically strong to penetrate skin, increasing the permeability of encapsulated drug through skin.

Protein encapsulation in polymeric microneedles by photolithography

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Microneedle integrated transdermal patch for fast onset and sustained delivery of lidocaine.

Lidocaine as an analgesic is of particular interest in both acute and chronic pain conditions and is used via injections or transdermal patches. While injections are associated with problems such as patient incompliance, topical administration of lidocaine using patches is less efficient due to variability of drug absorption among individuals, slower drug permeation through the skin, and hence a resultant undesirable delay in analgesic effects. To address this clinical problem, we developed a microneedle integrated transdermal patch (MITP), using a photolithography based process, in which microneedles create micrometer-sized channels in the skin to deliver lidocaine rapidly, while the reservoir patch holding the bulk of the drug enables higher drug loading and carries on to release the drug for prolonged periods. We demonstrated a new approach of drug delivery using microneedles, where drugs diffuse out of microneedles through the porous channels left by dissolving drug particles. MITP was shown to be able to encapsulate up to 70 mg of lidocaine. In vitro permeation through rat skin demonstrated that MITP delivered a significantly higher amount of lidocaine than a commercial patch and with a faster onset of drug permeation.

UV-curable pressure sensitive adhesive films: effects of biocompatible plasticizers on mechanical and adhesion properties

We developed a new approach to fabricate pressure sensitive adhesive (PSA) hydrogel films for dermatological applications. These hydrogel films were fabricated using polyvinylpyrrolidone (PVP), poly(ethylene glycol) diacrylate (PEGDA) and polyethylene glycol (PEG) with/without propylene glycol (PG) via photo-polymerization. Hydrogel films with a thickness ranging from 130 to 1190 μm were obtained. The surface morphology and drug distribution within the films were found to be uniform. The effects of different factors (polymeric composition, i.e., PEG/PG presence and film thickness) on the functional properties (i.e., rheological and mechanical properties, adhesion performance and drug distribution) of the films were investigated. The addition of plasticizers, namely PEG and PG, resulted in a simultaneous increase in elasticity and adhesiveness of these hydrogels, via the formation of hydrogen bonds, which has a direct correlation with their adhesion properties. The new approach is potentially useful for industrial applications, due to the simple procedure, precise control over film thickness, minimal usage of solvents and adjustable mechanical, rheological and adhesive properties.

A miniaturized flow-through cell to evaluate skin permeation of endoxifen

Endoxifen, an anti-estrogenic agent, has been recently implicated in the use of breast cancer. Its physicochemical properties make it a good candidate for transdermal delivery. However, as an investigative drug, its limited supply makes it difficult to conduct extensive pre-formulation studies. To address this issue, a miniaturized flow-through diffusion cell has been fabricated that utilized minimal amounts of the drug for in vitro skin permeation studies. The novel flow-through cells have been validated against horizontal diffusion cells and shown to cause no noticeable damage to the applied skin, as observed by histological sectioning. The cells were also demonstrated to be useful in search of suitable enhancers for endoxifen. Endoxifen permeation using permeation enhancers was tested by using this new device and limonene was found to achieve highest flux, attaining the requirement for clinical applications. The fabricated cells can thus be useful in carrying out pre-formulation studies for expensive, new drug entities, both in industrial as well as academic research.

NANO/MICROSCALE TECHNOLOGIES FOR DRUG DELIVERY

Nano- and microscale technologies have made a marked impact on the development of drug delivery systems. The loading efficiency and particle size of nano/micro particles can be better controlled with these new technologies than conventional methods. Moreover, drug delivery systems are moving from simple particles to smart particles and devices with programmable functions. These technologies are also contributing to in vitro and in vivo drug testing, which are important to evaluate drug delivery systems. For in vitro tests, lab-on-a-chip models are potentially useful as alternatives to animal models. For in vivo test, nano/micro-biosensors are developed for testing chemicals and biologics with high sensitivity and selectivity. Here, we review the recent development of nanoscale and microscale technologies in drug delivery including drug delivery systems, in vitro and in vivo tests.

Polymeric Microneedle Array Fabrication by Photolithography

This manuscript describes the fabrication of polymeric microneedle (MN) arrays by photolithography. It involves a simple mold-free process by using a photomask consisting of embedded micro-lenses. Embedded micro-lenses were found to influence MN geometry (sharpness). Robust MN arrays with tip diameters ranging between 41.5 µm ± 8.4 µm and 71.6 µm ± 13.7 µm, with two different lengths (1,336 µm ± 193 µm and 957 µm ± 171 µm) were fabricated. These MN arrays may provide potential applications in delivery of low molecular and macromolecular therapeutic agents through skin.

Microfluidic devices for drug discovery and analysis

Abstract: Microdevices, since their inception in the last decade of the twentieth century, have changed our view of science, due to their potential applications in fields ranging from optics, semiconductors and the microelectronics industry to drug discovery and development, point-of-care clinical diagnostics, sensitive bioanalytical systems and other areas of the biological sphere. In this chapter we review the potential applications of microfluidic platforms for drug discovery applications comprising high-throughput screening in target selection, lead identification/optimization and preclinical testing. Application of microfluidics in chemical analysis, as well as analysis of metabolites in blood for studying pathology, is also discussed.

Regulation of cosmetics

Cosmetic providers, be it a manufacturer or a distributor, have legal responsibility to ensure the safety and quality of the merchandise. Compliance to the regulation is highly recommended because it ensures product safety and minimizes unintended adverse effects, benefitting both the manufacturers and the consumers. In this chapter, the cosmetic legislation and regulation in major markets will be reviewed to facilitate a greater understanding of the different requirements in the respective markets and the subsequent adoption of the recommendations provided by the respective legislatures.