Doxorubicin (DOX), an anthracycline, is widely used in cancer treatment by interfering RNA and DNA synthesis. Its broad antitumour spectrum makes it an effective therapy for a wide array of cancers. However, the prevailing drug-resistant cancer has proven to be a significant drawback to the success of the conventional chemotherapy regime and DOX has been identified as a major hurdle. Furthermore, the clinical application of DOX has been limited by rapid breakdown, increased toxicity, and decreased half-time life, highlighting an urgent need for more innovative delivery methods. Although advancements have been made, achieving a complete cure for cancer remains elusive. The development of nanoparticles offers a promising avenue for the precise delivery of DOX into the tumour microenvironment, aiming to increase the drug concentration at the target site while reducing side effects. Despite the good aspects of this technology, the classical nanoparticles struggle with issues such as premature drug leakage, low bioavailability, and insufficient penetration into tumours due to an inadequate enhanced permeability and retention (EPR) effect. Recent advancements have focused on creating stimuli-responsive nanoparticles and employing various chemosensitisers, including natural compounds and nucleic acids, fortifying the efficacy of DOX against resistant cancers. The efforts to refine nanoparticle targeting precision to improve DOX delivery are reviewed. This includes using receptor-mediated endocytosis systems to maximise the internalisation of drugs. The potential benefits and drawbacks of these novel techniques constitute significant areas of ongoing study, pointing to a promising path forward in addressing the challenges posed by drug-resistant cancers.
The skin functions as a formidable barrier, particularly the stratum corneum, effectively restricting the penetration of most substances, including therapeutic agents. To circumvent this barrier, skin penetration enhancers (SPEs) are frequently employed to transiently increase skin permeability, facilitating drug absorption without causing irritation or damage. Despite advancements in dermal formulation development, a deeper understanding of the fundamental science underpinning drug delivery via SPEs remains essential. This review delivers a critical update on conventional SPEs, exploring their mechanisms in promoting drug permeation across the skin. In addition to offering an overview of percutaneous drug delivery, we examine the prevailing theories on how SPEs enhance drug transport. Furthermore, we address the intricate interplay between SPEs, drugs and the skin, providing valuable insights into how the molecular properties and permeation behaviours of SPEs influence their efficacy. This comprehensive review aims to support the ongoing development of optimised drug delivery systems for dermal applications by elucidating the complexities and challenges involved in using SPEs effectively.
Dental caries, driven predominantly by Streptococcus mutans, remains a significant global challenge. Conventional treatments often fall short due to antimicrobial resistance and limited efficacy. Enterocin CC2, a potent bacteriocin, offers a promising alternative but is hindered by stability and delivery challenges. This study pioneers the development of a cutting-edge microemulsion designed to enhance the stability, bioavailability, and antimicrobial potency of enterocin CC2 against S. mutans. A comprehensive screening of 124 formulations was conducted, evaluating thermodynamic stability, cytotoxicity, and antioxidant potential. The optimized formulation underwent rigorous analysis for physicochemical properties, antimicrobial activity, and long-term stability under varied storage conditions. The innovative microemulsion formulation, incorporating 0.5 mg/mL enterocin CC2, 0.5% surfactant blend (Tween 80 + PEG 400, 1:1), and 0.5% oil, demonstrated micro-sized droplets (88.50-92.10 nm), exceptional thermodynamic stability, and robust antimicrobial efficacy. Remarkably, it reduced the time to eradicate S. mutans UKMCC 1019 from 8 h (unformulated) to 5 h, outperforming 0.2% w/v chlorhexidine and 0.5 mg/mL nisin. Stability tests confirmed consistent performance in pH, viscosity, and antimicrobial activity for up to six weeks across various temperatures, with no detectable cytotoxicity. This study introduces a groundbreaking microemulsion formulation that redefines antimicrobial therapy for S. mutans. By leveraging the enhanced stability and rapid action of enterocin CC2, this innovation offers a transformative approach to oral health management, paving the way for next-generation antimicrobial solutions.