Triple-negative breast cancer is considered the most aggressive type of breast cancer among women and the lack of expressed receptors has made treatment options substantially limited. Recently, various types of nanoparticles have emerged as a therapeutic option against TNBC, to elevate the therapeutic efficacy of the existing chemotherapeutics. Among the various nanoparticles, lipid-based nanoparticles (LNPs) viz. liposomes, nanoemulsions, solid lipid nanoparticles, nanostructured lipid nanocarriers, and lipid–polymer hybrid nanoparticles are developed for cancer treatment which is well confirmed and documented. LNPs include various therapeutic advantages as compared to conventional therapy and other nanoparticles, including increased loading capacity, enhanced temporal and thermal stability, decreased therapeutic dose and associated toxicity, and limited drug resistance. In addition to these, LNPs overcome physiological barriers which provide increased accumulation of therapeutics at the target site. Extensive efforts by the scientific community could make some of the liposomal formulations the clinical reality; however, the relatively high cost, problems in scaling up the formulations, and delivery in a more targetable fashion are some of the major issues that need to be addressed. In the present review, we have compiled the state of the art about different types of LNPs with the latest advances reported for the treatment of TNBC in recent years, along with their clinical status and toxicity in detail.

One of the major aggressive factors that affect gastric injury is non-steroidal anti-inflammatory drugs (NSAIDs). Indomethacin (Indo) showed higher potentiality in gastric injury over conventional NSAIDs. Piceatannol (PIC) is a natural polyphenolic stilbene that possesses potent antioxidant and anti-inflammatory properties. The gastroprotective properties of PIC have been overlooked previously. Hence, we aim to study gastric injury induced by Indo and the protective action manifested by PIC, as well as to elucidate the likely underlying mechanisms of action in a rat model. The rats have been treated with vehicle, Indo alone, combined treatment with Indo, and PIC at (5 mg/kg or 10 mg/kg), respectively. The rats were also treated with Indo and omeprazole. In our study, we found that PIC at both 5 and 10 mg/kg doses was effective by averting the rise in ulcer and lesion indices, acid production, and histological variations persuaded by Indo. Mechanistically, PIC significantly reduced lipid peroxidation product (MDA), increased the GSH content, and enhanced SOD and CAT activity. In addition, PIC exhibits a distinct reduction in the levels of inflammatory parameters (Cox-2, IL-6, TNF-α, and NFκB). Contrastingly, PIC augmented both mucin and PGE2 content. Moreover, PIC fostered angiogenesis by increasing the expression of proangiogenic factors (VEGF, bFGF, and PDGF). Overall, the above results suggest PIC exhibits a potential protective effect against Indo-induced gastric ulcers by the antioxidant, anti-inflammatory, and angiogenic mechanisms.

In the present work, novel modality for lung cancer intervention has been explored. Primary literature has established the potential role of cyclooxygenase-2 (COX-2) inhibitor in regression of multiple forms of carcinomas. To overcome its poor water solubility and boost anticancer activity, etoricoxib (ETO) was chosen as a therapeutic candidate for repurposing and formulated into a nanoemulsion (NE). The prepared ETO loaded NE was characterized for the surface charge, droplet size, surface morphology, and in vitro release. The optimized ETO loaded NE was then investigated for its anticancer potential employing A549 lung cancer cell line via cytotoxicity, apoptotic activity, mitochondrial membrane potential activity, cell migration assay, cell cycle analysis, Caspase-3, 9, and p53 activity by ELISA and molecular biomarker analysis through RT-PCR test. The developed ETO-NE formulation showed adequate homogeneity in the droplet size distribution with polydispersity index (PDI) of (0.2 ± 0.03) and had the lowest possible droplet size (124 ± 2.91 nm) and optimal negative surface charge (−8.19 ± 1.51 mV) indicative of colloidal stability. The MTT assay results demonstrated that ETO-NE exhibited substantial anticancer activity compared to the free drug. The ETO-NE showed a substantially potent cytotoxic effect against lung cancer cells, as was evident from the commencement of apoptosis/necrotic cell death and S-phase cell cycle arrests in A549 cells. The study on these molecules through RT-PCR confirmed that ETO-NE is significantly efficacious in mitigating the abundance of IL-B, IL-6, TNF, COX-2, and NF-kB as compared to the free ETO and control group. The current study demonstrates that ETO-NE represents a feasible approach that could provide clinical benefits for lung cancer patients in the future.

The present study aimed to optimize luliconazole nanoemulsion using Box–Behnken statistical design, which was further incorporated into the polymeric gel of Carbopol 934. The formulation was characterized for its size, entrapment efficiency, ex vivo permeation, and mechanism of release. The size of the dispersed globules of the optimized drug-loaded nanoemulsion was found to be 17 ± 3.67 nm with a polydispersity index (PDI) less than 0.5. Although the surface charge was recorded at –9.53 ± 0.251, the stability was maintained by the polymeric matrix that prevented aggregation and coalescence of the dispersed globules. The luliconazole-nanoemulgel (LUL-NEG) was characterized for drug content analysis, viscosity, pH, and refractive index, where the results were found to be 99.06 ± 0.59%, 9.26 ± 0.08 Pa.s, 5.65 ± 0.17, and 1.31 ± 0.08, respectively. The permeation across the rat skin was found to be significantly higher with LUL-NEG when compared with LUL gel. Furthermore, the skin irritation test performed in experimental animals revealed that the blank NEG, as well as the LUL-NEG, did not produce any signs of erythema following 48 h exposure. In addition, the histopathological findings of the experimental skins reported no abnormal signs at the formulation application site. Finally, the NEG formulation was found to create a statistically significant zone of inhibition ( < 0.05) when compared to all other test groups. Overall, it could be summarized that the nanoemulgel approach of delivering luliconazole across the skin to treat skin fungal infections could be a promising strategy.

This study aimed to develop and evaluate sustained-release (SR) long-acting oral nanocomposites in-situ gelling films of resveratrol (Rv) to treat colorectal cancer. In these formulations, Rv-Soy protein (Rv-Sp) wet granules were prepared by the kneading method and then encapsulated in the sodium alginate (NA) dry films. The prepared nanocomposite in-situ gels films were characterized using dynamic light scattering, Fourier-transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy. The optimized formulations were further evaluated based on drug encapsulation efficiency, pH-drug release profile, swelling study, and storage time effects. The optimized formulation was tested for its anticancer activity against colorectal cancer cells using the cytotoxicity assessment, apoptosis testing, cell cycle analysis, gene expression analysis, and protein estimation by the reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay methods, respectively. The optimum film showed encapsulation efficiency of 97.87% ± 0.51 and drug release of 14.45% ± 0.043 after 8 h. All physiochemical characterizations confirmed, reasoned, and supported the drug release experiment’s findings and the encapsulation assay. The Rv nanocomposite formulation showed concentration-dependent cytotoxicity enhanced apoptotic activity as compared to free Rv (p < 0.05). In addition, Rv nanocomposite formulation caused a significant increase in Bcl-2-associated protein X (Bax) and a decrease in expression of B-cell lymphoma 2, interleukin 1 beta, IL-6, and tumor necrosis factor-alpha (Bcl2, IL-1β, IL-6, and TNF-α respectively) compared to that of free Rv in HCT-116 cells. These results suggest that long-acting Rv nanocomposite gels could be a promising agent for colorectal cancer treatment.

Doxorubicin (DOX), a common chemotherapeutic agent, suffers serious adverse effects including hepatotoxicity. Mokko lactone (ML) is a guainolide sesquiterpene with promising biological activities. The study aimed to evaluate the protection offered by ML against hepatotoxicity induced by DOX in rats. Our data indicated ML exhibited protective effects as evidenced by ameliorating the rise in serum activities of alanine transaminase, aspartate transaminase and alkaline phosphatase. This was confirmed histologically as ML prevented DOX-induced pathological alteration in liver architecture. Further, ML administration significantly prevented malondialdehyde accumulation, glutathione depletion and superoxide dismutase and catalase exhaustion. Antioxidant action of ML was associated with enhanced expression of the nuclear translocation of NF-E2-related factor 2 (Nrf2) and a lower expression of forkhead box protein O1 (FOXO1). Also, ML showed potent anti-inflammatory activities highlighted by decreased expression of interleukin 6, tumor necrosis factor α and nuclear factor κB (NF-κB). The anti-apoptotic effects of ML were associated with decreased Bax and enhanced Bcl-2 mRNA expression in liver tissues. ML caused a significant up-regulation in the expression of silent information regulator 1 (Sirt-1). Therefore, it can be concluded that ML prevents liver injury caused by DOX. This could partially be due to the ML regulatory activities on Sirt-1/FOXO1/NF-κB axis.