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  1. Gunawan M, Efendi A, Ramadon D, Liew CV, Chutoprapat R
    Expert Opin Drug Deliv, 2026 Nov;23(11):2059-2087.
    PMID: 42779272 DOI: 10.1080/17425247.2026.2739504
    INTRODUCTION: Skin delivery provides an alternative drug administration, although its effectiveness is limited by the stratum corneum barrier. Cubosomes, as third-generation lipid nanoparticles with bicontinuous cubic liquid crystalline structures, have emerged as promising nanocarriers that enhance skin penetration, sustain drug release, improve bioavailability, and minimize toxicity.

    AREAS COVERED: This review discusses the biopharmaceutical mechanisms of cubosome-mediated skin delivery, including bioadhesion, stratum corneum lipid fluidization, controlled release, enhanced cellular uptake, and improved bioavailability. Literature from 2006-2026 was collected from Scopus, PubMed, and patent databases, covering localized applications such as dermatological disorders, wound healing, fungal infections, alopecia, inflammatory skin diseases, and oncology, as well as systemic therapies including rheumatoid arthritis, gout, diabetes mellitus, and hormone replacement therapy. Recent advances, including microneedle integration, thermosensitive hydrogels, stimuli-responsive systems, and surface-engineered cubosomes, are also highlighted.

    EXPERT OPINION: Cubosomes represent a promising platform for advanced skin delivery. Optimal performance depends on the therapeutic goal, with systemic delivery requiring enhanced permeation and sustained absorption, whereas localized therapy prioritizes intradermal retention and tissue depot formation with minimal systemic exposure. Despite strong preclinical evidence, further studies on long-term safety, manufacturing standardization, and clinical validation are essential for successful clinical translation and commercialization of cubosome-based skin delivery.

  2. Dalimunthe A, Carensia Gunawan M, Dhiya Utari Z, Dinata MR, Halim P, Estherina S Pakpahan N, et al.
    Front Pharmacol, 2024;15:1461478.
    PMID: 39605919 DOI: 10.3389/fphar.2024.1461478
    Lupeol, a naturally occurring lupane-type pentacyclic triterpenoid, is widely distributed in various edible vegetables, fruits, and medicinal plants. Notably, it is found in high concentrations in plants like Tamarindus indica, Allanblackia monticola, and Emblica officinalis, among others. Quantitative studies have highlighted its presence in Elm bark, Olive fruit, Aloe leaf, Ginseng oil, Mango pulp, and Japanese Pear bark. This compound is synthesized from squalene through the mevalonate pathway and can also be synthetically produced in the lab, addressing challenges in natural product synthesis. Over the past four decades, extensive research has demonstrated lupeol's multifaceted pharmacological properties, including anti-inflammatory, antioxidant, anticancer, and antibacterial effects. Despite its significant therapeutic potential, clinical applications of lupeol have been limited by its poor water solubility and bioavailability. Recent advancements have focused on nano-based delivery systems to enhance its bioavailability, and the development of various lupeol derivatives has further amplified its bioactivity. This review provides a comprehensive overview of the latest advancements in understanding the pharmacological benefits of lupeol. It also discusses innovative strategies to improve its bioavailability, thereby enhancing its clinical efficacy. The aim is to consolidate current knowledge and stimulate further research into the therapeutic potential of lupeol and its derivatives.
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