Search

We report a case of vascularised fibula osteocutaneous flap used for composite cervical spinal and posterior pharyngeal wall reconstruction, in a patient with recurrent skull base chordoma, resected by an anterior approach via median labio-mandibular glossotomy approach. Bone stability and pharyngeal wall integrity were simultaneously restored

Dexamethasone (Dex) is a popular and highly potent anti-inflammatory drug, frequently used to treat a wide range of inflammatory disorders. However, the existing oral and parenteral delivery modes have several limitations, including systemic adverse effects and reduced patient compliance. This study aimed to develop a biodegradable microneedle (MN)-based transdermal delivery system capable of sustained, safe and effective delivery of Dex. A Quality by Design (QbD) approach was applied to design the Dex-loaded MN arrays. The formulation variables were optimized using a central composite design (CCD) model, generated with the statistical software package Design- Expert®. The optimized MNs were sharp, with heights ranging between 800 and 900 µm, appropriate for transdermal delivery. The MN arrays did not exhibit any cytotoxic effects on the fibroblast and keratinocyte cells. Moreover, the ex vivo studies confirmed the enhanced efficacy of MN-mediated skin permeation of Dex compared to passive permeation of drug solution. Finally, the in vivo anti-inflammatory efficacy was investigated using the carrageenan-induced rat paw edema model. The efficacy of the MN arrays to inhibit paw edema formation was found to be comparable to that of intravenous Dex injection and significantly greater than topical solution. Cytokine analysis also revealed that application of MN arrays downregulated the expressions of pro-inflammatory cytokines and upregulated the expressions of anti-inflammatory cytokines. Overall, the findings suggest that MN array could be a safe, easy, effective and minimally invasive alternative to the existing means of Dex delivery and could potentially be used for the treatment of inflammatory disorders., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jingyuan Wen reports financial support was provided by New Zealand Pharmacy Education and Research Foundation (NZPERF)., (Copyright © 2023. Published by Elsevier B.V.)

Centella asiatica, a medicinal herb used for wound healing, has a limited effect when delivered as an ointment. Centella asiatica's active component asiatic acid (AA) increases extracellular matrix development and reduces inflammation but cannot penetrate the stratum corneum to access deeper skin layers. To bypass the stratum corneum, we formulated two types of AA-loaded microneedle arrays. We fabricated, characterised and optimised a dissolving array made from chitosan and PVA and a hydrogel array made from chitosan and PVP. Both needles were strong and long enough to pierce the epidermis without breaking. Both were biocompatible with keratinocytes and fibroblasts (>75% viability at 100% concentration) and showed a sustained drug release over 48 h. The hydrogel microneedle released more AA (52.2%) than the dissolving formulation (26.4%); thus, we evaluated them in an excisional rat model. The hydrogel microneedle arrays significantly increased the rate of wound closure compared to the control. This research has shown that the chitosan-PVA hydrogel microneedles could penetrate the epidermis, effectively release AA, and increase the wound closure rate. This AA-loaded delivery system shows promise as a natural treatment for wound healing and may be applied to other bioactive compounds with similar physiochemical properties in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Application of modern delivery techniques to natural bioactive products improves their permeability, bioavailability, and therapeutic efficacy. Many natural products have desirable biological properties applicable to wound healing but are limited by their inability to cross the stratum corneum to access the wound. Over the past two decades, modern systems such as microneedles, lipid-based vesicles, hydrogels, composite dressings, and responsive formulations have been applied to natural products such as curcumin or aloe vera to improve their delivery and efficacy. This article reviews which natural products and techniques have been formulated together in the past two decades and the success of these applications for wound healing. Many cultures prefer natural-product-based traditional therapies which are often cheaper and more available than their synthetic counterparts. Improving natural products' effect can provide novel wound-healing therapies for those who trust traditional compounds over synthetic drugs to reduce medical inequalities.

Nicotine replacement therapy (NRT) is widely used to limit the withdrawal symptoms associated with cigarette smoking cessation. However, the available NRT formulations are limited by their short release profiles, requiring frequent administrations along with local side effects. Thus, the objective of this study is to develop an NRT formulation that offers prolonged, sustained nicotine release. Thermoresponsive in situ gelling systems containing nicotine were prepared using poloxamer 407 (P407) and poloxamer 188 (P188). The system was optimized using a three-factor, two-level full factorial design (2 3 ). A formulation composed of P407 (20% w/w ), P188 (5% w/w ), and loaded with nicotine (0.5% w/w ) exhibited sol-to-gel transition at a suitable temperature close to physiological temperature (30 °C). The rheological analysis demonstrated a Newtonian-like flow at room temperature, suggesting ease of administration via injection, and semisolid gel status at physiological temperature. The optimized formulation successfully sustained nicotine in vitro release over 5 days following single administration. The findings suggest that poloxamer based in situ gelling systems are promising platforms to sustain the release of nicotine.

Dexamethasone is a fluorinated derivative of the natural glucocorticoid, cortisone, with a very high systemic anti-inflammatory effect. In this study, a simple and rapid high performance liquid chromatography (HPLC) method was developed and validated to quantify dexamethasone and its prodrug dexamethasone sodium phosphate in skin permeation studies. The separation of both the compounds was achieved on a Vydac Denali C 18 column(250 × 4.6 mm, 5 μm) with a mobile phase composed of 5 mM ammonium acetate buffer-acetonitrile-methanol (43:32:25, v/v) at a flow rate of 0.9 mL/min and UV detection at 240 nm. The standard curves were found to be linear in the range from 0.5 to 100 µg/mL for both the drugs and the method could successfully separate the drug peaks from interfering peaks of endogenous skin constituents. Accuracy values of both the drugs were within 98.60 to 108.60% (intra-day) and 98.70 to 107.20% (inter-day) and precision values were within 2% at the studied concentrations. The developed method was used to investigate the effect of microneedles on transdermal delivery of dexamethasone sodium phosphate. The hydrolysis of dexamethasone sodium phosphate to dexamethasone in the presence of rat skin homogenate and rat plasma was also evaluated to confirm the conversion that occurs during skin permeation and in the blood circulation. The skin permeation and deposition characteristics of microneedle-assisted diffusion were compared to those achieved by passive diffusion. The observed data demonstrated that transdermal permeation of dexamethasone is significantly enhanced with microneedle pretreatment of rat skin, showing a marked increase in flux and permeability coefficient, compared to passive diffusion. This simple isocratic HPLC method can, be effectively applied for the evaluation of skin permeation of topical/transdermal dexamethasone formulations., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Transdermal drug delivery offers several attractive advantages over the traditional oral and parenteral routes. Particularly, in case of paediatric patients, it helps to overcome the issues specific to this population, such as difficulty in swallowing and palatability of oral medicines as well as fear and pain associated with needles. However, due to the formidable barrier characteristic of the stratum corneum, it fails in the effective systemic delivery of broad range of therapeutic molecules, especially macromolecules and genetic material. Over the last two decades, microneedle technology has been portrayed as a strategy to infringe the stratum corneum, in a minimally invasive manner, and enable the successful passage of molecules by creating transient channels across the skin. There has been an exponential surge in the number of studies exploring the design, development and fabrication of microneedles. This article reviews the evolution of microneedle technology and provides a comprehensive summary of microneedle research to date. It provides a detailed overview of the microneedle types, advanced fabrication strategies including the biodegradability and compatibility of the new materials used in fabrication. Research on microneedle-mediated paediatric drug delivery as well as insights on the application of this novel technology has been discussed. The up-to-date progress in clinical translation of microneedles and the regulatory requirements for their commercialization are highlighted along with a brief perspective on the future prospects of microneedle-mediated paediatric drug delivery. This review proposes that advanced research can further contribute to the improved therapeutic efficiency of microneedle-based delivery of numerous molecules, which are otherwise difficult to administer via the conventional transdermal delivery mechanisms., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Growing concern on the application of synthetic mosquito repellents in the recent years has instigated the identification and development of better alternatives to control different mosquito-borne diseases. In view of above, present investigation evaluates the repellent activity of ethyl anthranilate (EA), a non-toxic, FDA approved volatile food additive against three known mosquito vectors namely, Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus under laboratory conditions following standard protocols. Three concentration levels (2%, 5% and 10% w/v) of EA were tested against all the three selected mosquito species employing K & D module and arm-in-cage method to determine the effective dose (ED 50 ) and complete protection time (CPT), respectively. The repellent activity of EA was further investigated by modified arm-in-cage method to determine the protection over extended spatial ranges against all mosquito species. All behavioural situations were compared with the well-documented repellent N,N-diethylphenyl acetamide (DEPA) as a positive control. The findings demonstrated that EA exhibited significant repellent activity against all the three mosquitoes species. The ED 50 values of EA, against Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus were found to be 0.96%, 5.4% and 3.6% w/v, respectively. At the concentration of 10% w/v, it provided CPTs of 60, 60 and 30min, respectively, against Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus mosquitoes. Again in spatial repellency evaluation, EA was found to be extremely effective in repelling all the three tested species of mosquitoes. Ethyl anthranilate provided comparable results to standard repellent DEPA during the study. Results have concluded that the currently evaluated chemical, EA has potential repellent activity against some well established mosquito vectors. The study emphasizes that repellent activity of EA could be exploited for developing effective, eco-friendly, acceptable and safer alternative to the existing harmful repellents for personal protection against different hematophagous mosquito species., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Hyperpigmentation is a dermal condition of melanocyte proliferation, induced by various factors like ultraviolet radiation producing reactive oxygen species, DNA damage, and apoptosis. The application of topical antioxidants through the different type of formulations can help to prevent oxidative damage to the skin. L-ascorbic acid (vitamin C) is a water-soluble compound and the most abundant antioxidant in human skin, but this vitamin is unstable and loses its potency with poor formulation strategies. Nanotechnology has been effectively used to promote stability and therapeutic activity of various drug molecules. With this context, the objective of the work was set to formulate a topical delivery system of vitamin C nanoparticles incorporated into the polymeric gel. Vitamin C (50 mg) was loaded into ethyl cellulose nanoparticles, of varying concentrations (50-250 mg), by the solvent evaporation method and subsequently incorporated into hydroxypropyl methyl cellulose gels (3, 5, and 7%). The formulations were characterized for various physico-chemical properties such as particle size, drug content, entrapment efficiency, and drug-polymer interactions. In vitro, drug release studies were conducted by using dialysis bag method and Franz diffusion cell for the nanoparticles and gel formulations, respectively. The optimized formulation exhibited sustained release over 8 h. The ex vivo skin permeation studies were performed and the amount of drug retained and released through the skin were determined. The results obtained from the study proved the potentiality and suitability of this novel system to treat hyperpigmentation.

Mosquito being the major medically important arthropod vector; requires utmost attention to reduce the sufferings and economic consequences of those living in the endemic regions. This is only possible by minimising the human-mosquito contact by an absolute preventing measure. However, unfortunately, such absolute measures are yet to be developed despite enormous efforts and huge investments worldwide. In the absence of vaccines for number of mosquito-borne diseases, repellents could be an attractive option for both military personal and civilians to minimise the risk of contacting different mosquito-borne diseases. However, to achieve this golden goal, the detailed knowledge of a particular repellent is must, including its mode of repellency and other relevant informations. Here, in the present article, an effort has been made to convey the best and latest information on repellents in order to enhance the knowledge of scientific community. The review offers an overview on mosquito repellents, the novel discoveries, and areas in need of attention such as novel repellent formulations and their future prospective., (Copyright © 2016 Elsevier B.V. All rights reserved.)