Novel nano-in-micro fabrication technique of diclofenac nanoparticles loaded microneedle patches for localised and systemic drug delivery.

Diclofenac, a nonsteroidal anti-inflammatory drug, is commonly prescribed for managing osteoarthritis, rheumatoid arthritis, and post-surgical pain. However, oral administration of diclofenac often leads to adverse effects. This study introduces an innovative nano-in-micro approach to create diclofenac nanoparticle-loaded microneedle patches aimed at localised, sustained pain relief, circumventing the drawbacks of oral delivery. The nanoparticles were produced via wet-milling, achieving an average size of 200 nm, and then incorporated into microneedle patches. These patches showed improved skin penetration in ex vivo tests using Franz-cell setups compared to traditional diclofenac formulations. In vivo tests on rats revealed that the nanoparticle-loaded microneedle patches allowed for quick drug uptake and prolonged release, maintaining drug levels in tissues for up to 72 h. With a systemic bioavailability of 57 %, these patches prove to be an effective means of transdermal drug delivery. This study highlights the potential of this novel microneedle delivery system in enhancing the treatment of chronic pain with reduced systemic side effects.

Mathematical modelling of nanoparticle-mediated topical drug delivery to skin tissue.

Nanoparticles have been extensively studied to improve drug delivery outcomes, however, their use in topical delivery remains controversial. Although the feasibility to cross the human skin barrier has been demonstrated in experiments, the risk of low drug concentration in deep tissue still limits the application. In this study, mathematical modelling is employed to examine the performance of nanoparticle-mediated topical delivery for sending drugs into the deep skin tissue. The pharmacokinetic effect is evaluated based on the drug exposure over time. As compared to the delivery using plain drugs, nanoparticle-mediated topical delivery has the potential to significantly improve the drug exposure in deep skin tissue. Modelling predictions denote that the importance of sufficient long-term drug-skin contact in achieving effective drug deposition in the deep skin tissue. The delivery outcomes are highly sensitive to the release rate. Accelerating the release from nanoparticles in stratum corneum is able to improve the drug exposure in stratum corneum and viable epidermis while resulting in the reductions in dermis and blood. The release rate in stratum corneum and viable epidermis should be well-designed below a threshold for generating effective drug accumulation in dermis and blood. A more localised drug accumulation can be achieved in the capillary-rich region of dermis by increasing the local release rate. The release rate in dermis needs to be optimised to increase the drug exposure in the dermis region where there are fewer blood and lymphatics capillaries. Results from this study can be used to improve the regimen of topical delivery for localised treatment.

Disulfiram-loaded immediate and extended release vaginal tablets for the localised treatment of cervical cancer.

OBJECTIVES: To develop and manufacture both immediate and sustained release vaginal tablets containing the anticancer drug disulfiram, which has the potential to be used as a non-invasive treatment for cervical cancer. METHODS: Disulfiram-loaded vaginal tablets were manufactured at pilot scale using the direct compression method. These tablets were tested in accordance with the European Pharmacopeia testing of solid dosage form guidelines. They were also tested using a biorelevant dissolution method as well as a dual-chambered release model designed to better mimic the dynamic nature of the vaginal vault. KEY FINDINGS: We have developed both immediate and sustained release vaginal tablets, which when manufactured at pilot scale are within the limits set by the European Pharmacopeia for the testing of solid dosage forms. Furthermore, these tablets are capable of releasing disulfiram in vitro using the dual-chambered release model at levels 25,000 times and 35,000 times greater than its IC50 concentration for the HeLa cervical cancer cell line. CONCLUSIONS: The successful pilot manufacture and testing of both the immediate and sustained release disulfiram-loaded vaginal tablets warrant further investigation, using an in-vivo model, to assess their potential for use as a non-invasive treatment option for cervical cancer.

The past, present and future in scaffold-based tendon treatments.

Tendon injuries represent a significant clinical burden on healthcare systems worldwide. As the human population ages and the life expectancy increases, tendon injuries will become more prevalent, especially among young individuals with long life ahead of them. Advancements in engineering, chemistry and biology have made available an array of three-dimensional scaffold-based intervention strategies, natural or synthetic in origin. Further, functionalisation strategies, based on biophysical, biochemical and biological cues, offer control over cellular functions; localisation and sustained release of therapeutics/biologics; and the ability to positively interact with the host to promote repair and regeneration. Herein, we critically discuss current therapies and emerging technologies that aim to transform tendon treatments in the years to come.

Development of disulfiram-loaded vaginal rings for the localised treatment of cervical cancer.

Cervical cancer is the third most prevalent cancer in women and disproportionately affects those in low resource settings due to limited programs for screening and prevention. In the developed world treatment for the disease in the non-metastasised state usually takes the form of surgical intervention and/or radiotherapy. In the developing world such techniques are less widely available. This paper describes the development of an intravaginal ring for the localised delivery of a chemotherapeutic drug to the cervix that has the potential to reduce the need for surgical intervention and will also provide a novel anti-cancer therapy for women in low resource settings. Disulfiram has demonstrated antineoplastic action against prostate, breast and lung cancer. Both PEVA and silicone elastomer were investigated for suitability as materials in the manufacture of DSF eluting intravaginal rings. DSF inhibited the curing process of the silicone elastomer, therefore PEVA was chosen as the material to manufacture the DSF-loaded vaginal rings. The vaginal rings had an excellent content uniformity while the DSF remained stable throughout the manufacturing process. Furthermore, the rings provided diffusion controlled release of DSF at levels well in excess of the IC50 value for the HeLa cervical cancer cell line.