25 research outputs found
Accelerating Topical Anaesthesia Using Microneedles
No full text<b><i>Background/Aims:</i></b> Topical anaesthetics reduce pain during venous access procedures in children. However, clinical use is hindered by a significant anaesthetic onset time. Restricted diffusion of the topical anaesthetic through the stratum corneum barrier is the principal reason for the delayed onset. Microneedles can painlessly pierce the skin. This study evaluated microneedle pre-treatment of ex vivo human skin as a means to increase the rate of tetracaine permeation, in order to accelerate the onset of anaesthesia. <b><i>Methods:</i></b> Franz-type diffusion cells were used to determine permeation of a commercial tetracaine formulation, Ametop gel, through human skin epidermis. Microneedle-assisted permeation was compared to untreated epidermis. Upon completion of the permeation studies, the epidermal membranes were visually characterised. <b><i>Results:</i></b> At 30 min, 5.43 µg/cm<sup>2</sup> of tetracaine had permeated through the untreated membrane compared to 12.13 µg/cm<sup>2</sup> through the microneedle-treated membrane. Insertion of a hypodermic needle created a large single channel in the epidermis (approx. 4,250 μm<sup>2</sup>) whilst the punctured surface area following microneedle treatments was estimated to be 75,000 μm<sup>2</sup>. <b><i>Conclusion:</i></b> Pre-treatment of skin with microneedles significantly enhances the permeation of tetracaine. Microneedles have the potential to more than halve the onset time for anaesthesia when applying Ametop gel.</jats:p
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Development of an ex vivo human skin model for intradermal vaccination : tissue viability and Langerhans cell behaviour
No full textThe presence of resident Langerhans cells (LCs) in the epidermis makes the skin an attractive target for DNA vaccination. However, reliable animal models for cutaneous vaccination studies are limited. We demonstrate an ex vivo human skin model for cutaneous DNA vaccination which can potentially bridge the gap between pre-clinical in vivo animal models and clinical studies. Cutaneous transgene expression was utilised to demonstrate epidermal tissue viability in culture. LC response to the culture environment was monitored by immunohistochemistry. Full-thickness and split-thickness skin remained genetically viable in culture for at least 72 h in both phosphate-buffered saline (PBS) and full organ culture medium (OCM). The epidermis of explants cultured in OCM remained morphologically intact throughout the culture duration. LCs in full-thickness skin exhibited a delayed response (reduction in cell number and increase in cell size) to the culture conditions compared with split-thickness skin, whose response was immediate. In conclusion, excised human skin can be cultured for a minimum of 72 h for analysis of gene expression and immune cell activation. However, the use of split-thickness skin for vaccine formulation studies may not be appropriate because of the nature of the activation. Full-thickness skin explants are a more suitable model to assess cutaneous vaccination ex vivo
Microneedle mediated delivery of nanoparticles into human skin
No full textThe development of novel cutaneous delivery technologies that can produce micron-sized channels within the outermost skin layers has stimulated interest in the skin as an interface for localised and systemic delivery of macromolecular and nanoparticulate therapeutics. This investigation assesses the contribution of physicochemical factors to the rate and extent of nanoparticle delivery through microchannels created in a biological tissue, the skin, by novel delivery technologies such as the microneedle array.
The hydrodynamic diameter, zeta potential and surface morphology of a representative fluorescent nanoparticle formulation were characterised. Permeation studies using static Franz-type diffusion cells assessed (i) the diffusion of nanoparticle formulations through a model membrane containing uniform cylindrical microchannels of variable diameter and (ii) nanoparticle penetration across microneedle treated human skin.
Wet-etch microneedle array devices can be used to significantly enhance the intra/transdermal delivery of nanoparticle formulations. However the physicochemical factors, microchannel size and particle surface charge, have a significant influence on the permeation and subsequent distribution of a nanoparticle formulation within the skin. Further work is required to understand the behaviour of nanoparticle formulations within the biological environment and their interaction with the skin layers following disruption of the skin barrier with novel delivery devices such as the microneedle array
Gene delivery to the epidermal cells of human skin explants using microfabricated microneedles and hydrogel formulations
No full textPurpose
Microneedles disrupt the stratum corneum barrier layer of skin creating transient pathways for the enhanced permeation of therapeutics into viable skin regions without stimulating pain receptors or causing vascular damage. The cutaneous delivery of nucleic acids has a number of therapeutic applications; most notably genetic vaccination. Unfortunately non-viral gene expression in skin is generally inefficient and transient. This study investigated the potential for improved delivery of plasmid DNA (pDNA) in skin by combining the microneedle delivery system with sustained release pDNA hydrogel formulations.
Materials and Methods
Microneedles were fabricated by wet etching silicon in potassium hydroxide. Hydrogels based on Carbopol polymers and thermosensitive PLGA-PEG-PLGA triblock copolymers were prepared. Freshly excised human skin was used to characterise microneedle penetration (microscopy and skin water loss), gel residence in microchannels, pDNA diffusion and reporter gene (β-galactosidase) expression.
Results
Following microneedle treatment, channels of approximately 150–200 μm depth increased trans-epidermal water loss in skin. pDNA hydrogels were shown to harbour and gradually release pDNA. Following microneedle-assisted delivery of pDNA hydrogels to human skin expression of the pCMVβ reporter gene was demonstrated in the viable epidermis proximal to microchannels.
Conclusions
pDNA hydrogels can be successfully targeted to the viable epidermis to potentially provide sustained gene expression therein
Pocketed microneedles for rapid delivery of a liquid-state botulinum toxin A formulation into human skin
No full textBotulinum toxin A (BT) is used therapeutically for the treatment of primary focal hyperhidrosis, a chronic debilitating condition characterised by over-activity of the eccrine sweat glands. Systemic toxicity concerns require BT to be administered by local injection, which in the case of hyperhidrosis means multiple painful intradermal injections by a skilled clinician at 6-monthly intervals. This study investigates the potential of a liquid-loaded pocketed microneedle device to deliver botulinum toxin A into the human dermis with the aim of reducing patient pain, improving therapeutic targeting and simplifying the administration procedure. Initially, β-galactosidase was employed as a detectable model for BT to (i) visualise liquid loading of the microneedles, (ii) determine residence time of a liquid formulation on the device and (iii) quantify loaded doses. An array of five stainless steel pocketed microneedles was shown to possess sufficient capacity to deliver therapeutic doses of the potent BT protein. Microneedle-mediated intradermal delivery of β-galactosidase and formaldehyde-inactivated botulinum toxoid revealed effective deposition and subsequent diffusion within the dermis. This study is the first to characterise pocketed microneedle delivery of a liquid formulation into human skin and illustrates the potential of such systems for the cutaneous administration of potent proteins such as BT. A clinically appropriate microneedle delivery system for BT could have a significant impact in both the medical and cosmetic industries
Microneedle facilitated delivery of pDNA encoding HBsAg to human skin: potential for genetic vaccination [Abstract]
No full text
European Randomized multicenter study of goserelin (Zoladex) in the management of mastalgia
No full textBackground
Breast pain is a common symptom in patients attending breast clinics. The purpose of this study was to evaluate the efficacy of goserelin (Zoladex) as compared with sham injection in patients with mastalgia.
Study design
One hundred forty-seven premenopausal women were randomized to treatment with either goserelin injection (3.6 mg/month) or sham injection for a total of 6 injections. Patients' daily self-assessment of breast pain using Cardiff breast pain chart was recorded during the 6-month treatment period and for 6 months in the posttreatment period.
Results
A significant treatment difference between the 2 groups in favor of goserelin was noted during the treatment period. Mean breast pain score improved by 67% in the goserelin group and 35% in the sham group during the treatment period. The mean pain scores increased in both groups in the posttreatment period. No significant posttreatment difference was found between the two groups. Side effects were more common with goserelin than sham injection. Patients receiving goserelin experienced vaginal dryness, hot flushes, decreased libido, oily skin or hair, and a decrease in breast size more frequently than sham patients.
Conclusion
Goserelin is an effective short-term treatment for mastalgia. However, side effects are common, and thus, goserelin should be kept in reserve for patients who are refractory to other forms of treatment. Potentially, goserelin could be used to induce a rapid relief of symptoms that could be maintained with alternative therapies
Cutaneous DNA delivery and gene expression in ex vivo human skin explants via wet-etch microfabricated microneedles
No full textMicroneedle arrays increase skin permeability by forming channels through the outer physical barrier, without stimulating pain receptors populating the underlying dermis. It was postulated that microneedle arrays could facilitate transfer of DNA to human skin epidermis for cutaneous gene therapy applications. Platinum-coated “wet-etch� silicon microneedles were shown to be of appropriate dimensions to create microconduits, approximately 50 μm in diameter, extending through the stratum corneum (SC) and viable epidermis. Following optimisation of skin explant culturing techniques and confirmation of tissue viability, the ability of the microneedles to mediate gene expression was demonstrated using the β-galactosidase reporter gene. Preliminary studies confirmed localised delivery, cellular internalisation and subsequent gene expression of pDNA following microneedle disruption of skin. A combination of this innovative gene delivery platform and the ex vivo skin culture model will be further exploited to optimise cutaneous DNA delivery and address fundamental questions regarding gene expression in skin
