American Journal of PharmTech Research

β-Lapachone (β-Lap) is a naturally occurring ortho-naphthoquinone found in the heartwood of Handroanthus impetiginosus and other lapacho trees. The compound has been studied extensively due to its promising anticancer potential in cancer cells with high expression of NAD(P)H:quinone oxidoreductase 1 (NQO1). Reduction of β-Lap by NQO1 leads to the formation of a highly unstable hydroquinone intermediate which undergoes oxidation in a futile redox cycle, generating excessive amounts of ROS. The resultant oxidative stress can lead to DNA damage, hyperactivation of PARP1, reduction of NAD+ and ATP levels and cell death in cancer cells. Although β-Lap exhibits promising pharmacological effects, its poor solubility in water, problems with formulation and pharmacokinetics, possible toxic effects associated with dosing and limited therapeutic window limit the clinical applications of the parent compound. Therefore, various modifications of β-Lap structure were performed using the arylamino, alkoxy, thiosemicarbazone, oxime and prodrug strategies. Computer-assisted drug design approaches such as molecular docking, electronic-structure calculation and ADMET predictions serve as additional methods of selection of promising β-Lap derivatives before synthesis and testing. The present review gives a summary of the chemistry, physicochemical properties, SAR, pharmacology, synthetic and computational approaches to β-Lap and its derivatives [1-3,6]. The review was performed on published scientific papers based on β-lapachone, structural derivatives of β-lapachone, anticancer potential, molecular docking, and computational ADMET study. β-Lapachone was taken into account as the main parent compound, and structural derivatives, including arylamino, alkoxy, oxime, thiosemicarbazone, and other groups, were discussed. The computational methods, including molecular docking, were considered for the assessment of the interaction between the ligands and their targets (proteins) involved in the process of cancer development such as NQO1 and Topoisomerase IIα. Binding interactions, docking score, hydrogen bonding, hydrophobic, and π-π interactions were studied according to the reported studies. Besides, the pharmacokinetic and toxicity properties were also evaluated through ADMET prediction to obtain better anticancer agents [1,4,6,7]

Aim: Aim of the present research study is to formulate herbal anti-fungal cream with p-chloro-m-xylenol. Herbal extracts are becoming popular alternatives to synthetic treatments because they offer multi-target effects with fewer toxic side effects. formulation F1, F2, F3 were subjected for characterization and evaluation of physiochemical parameters like FTIR studies, color and odor, type of smear, irritancy test, spreadability test, washability test, antifungal test of formulation Conclusion: ointment showed white color with smooth texture and free of gritty particles. FTIR studies confirmed that PCMX, basil oil, terpineol oil, aloe vera gel with excipients does not show any significant change in peak hence, it is found to be compatible. All the test parameters evaluated were in acceptable range with no skin irritation. Anti-fungal studies were performed with standard control samples as Fluconazole against the fungal strain candida albicans by well diffusion method. All the formulation possesses effective anti-fungal properties. F1 showed 1.6 cm zone of inhibition, formulation F2 showed 2 cm and formulation F3 showed 2.1 cm zone of inhibition compared to standard sample fluconazole that is 1 cm. comparative study showed that there was minimum difference between F2 and F3 as anti-fungal action. By considering the entire test and result formulation F2 was found to be optimized formulation with effective anti-fungal activity.

Glioblastoma multiforme (GBM) is an aggressive primary brain tumor with limited therapeutic options, largely due to poor drug penetration across the blood–brain barrier (BBB). Capecitabine, a prodrug of 5-fluorouracil, has demonstrated potential against glioblastoma; however, its short half-life and limited brain delivery may restrict its therapeutic efficacy. This study aimed to develop and evaluate a thermoresponsive intranasal nanoemulsion-based in situ gel of capecitabine for potential nose-to-brain delivery in GBM therapy. Capecitabine-loaded nanoemulsion in situ gels were prepared using triolein, egg lecithin, and Pluronic F127 and F68 by emulsification followed by probe sonication. The formulations were evaluated for physicochemical characteristics, drug content, thermal compatibility, morphology, and in vitro drug release. The optimized formulation (F5) exhibited a gelation temperature of 33.2 ± 0.45 °C and a pH of 6.4, indicating suitability for intranasal administration. F5 showed an average droplet size of 219.7 nm, polydispersity index of 0.12, and zeta potential of −16.6 mV, indicating a uniform and stable nanoemulsion system. The drug content was 97.67 ± 1.564%. Differential scanning calorimetry confirmed compatibility between capecitabine and the formulation excipients, while scanning electron microscopy revealed spherical lipid droplets dispersed within the gel matrix. The optimized formulation demonstrated sustained drug release, achieving 99.64 ± 0.119% cumulative release over 8 h. Drug release kinetics followed the Higuchi and Korsmeyer–Peppas models, suggesting diffusion-controlled release. Overall, the developed thermoresponsive intranasal nanoemulsion-based in situ gel demonstrates promising physicochemical and drug-release characteristics for potential nose-to-brain delivery of capecitabine in glioblastoma therapy.