Hassan Nazia, Firdaus Salma, Padhi Santwana, Ali Asgar, Iqbal Zeenat
Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, Delhi 110062, India.
KIIT Technology Business Incubator, KIIT Deemed to be University, Bhubaneswar, Odisha, India.
Med Hypotheses. 2021 Mar;148:110515. doi: 10.1016/j.mehy.2021.110515. Epub 2021 Jan 26.
The rampant emergence of Candida albicans in the vagina and its ability to thrive as a biofilm has outstood the prevalence of candidal vulvovaginitis (CVV), a gender-based fungal infection approximately affecting 75% of the global female population. The biofilm represents a multidimensional microbial population, which often dictates prominent caveats of CVV such as increased fungal virulence, drug resistance and infection relapse/recurrence. Additionally, the conjugated issues of the ineffectiveness of conventional antifungals (azoles), prolonged treatment durations, compromised patient compliance, economic and social burden, exacerbates CVV complications as well. Henceforth, the current hypothesis narrates an investigational proposal for exploration and combination of naturally derived antibiofilm components with luliconazole (imidazole antifungal agent) as a new therapeutic paradigm against CVV. The purported hypothesis unravels a synergistic approach for fabricating Nanostructured Lipid Carriers, NLCs loaded transvaginal gel with dual APIs of natural (antibiofilm) as well as the synthetic (antifungal) origin to target high therapeutic efficacy, delivery, retention, controlled release and bioadhesion in a vaginal milieu. The multipronged effect of antibiofilm and antifungal agents will expectably enhance drug susceptibility thus, maintaining Minimum Inhibitory Concentration (MIC) against cells of C. albicans and targeting its biofilm in planktonic, adherent, and sessile phases. The effective disruption of a biofilm could further lower infection resistance and recurrence as well. In conclusion, the purported hypothesis could speed up the emergence of novel drug combinations and accelerates new product development with solid, synergistic, and complementary activities against C. albicans and its biofilm, making it amenable for generating pre-clinical and clinical results therebycreating a suitableroadmap for commercialization.
白色念珠菌在阴道中猖獗出现,且能够以生物膜的形式茁壮生长,这使得念珠菌性外阴阴道炎(CVV)的患病率居高不下。CVV是一种基于性别的真菌感染,全球约75%的女性人口受其影响。生物膜代表了一种多维微生物群体,它常常决定了CVV的一些突出问题,如真菌毒力增加、耐药性以及感染复发。此外,传统抗真菌药物(唑类)无效、治疗时间延长、患者依从性差、经济和社会负担等相关问题,也加剧了CVV的并发症。因此,当前的假设提出了一项研究方案,探索天然来源的抗生物膜成分与卢立康唑(咪唑类抗真菌剂)联合使用,作为对抗CVV的一种新的治疗模式。该假设揭示了一种协同方法,用于制备纳米结构脂质载体(NLCs),即负载有天然(抗生物膜)和合成(抗真菌)双重活性成分的经阴道凝胶,以实现高治疗效果、递送、保留、控释以及在阴道环境中的生物粘附。抗生物膜和抗真菌剂的多方面作用有望提高药物敏感性,从而维持对白色念珠菌细胞的最低抑菌浓度(MIC),并在浮游、粘附和固着阶段靶向其生物膜。生物膜的有效破坏还可进一步降低感染抗性和复发率。总之,该假设可以加速新型药物组合的出现,并加快新产品的开发,这些产品具有针对白色念珠菌及其生物膜的坚实、协同和互补活性,便于产生临床前和临床结果,从而为商业化创造合适的路线图。