Fisetin-Loaded Nanostructured Lipid Carriers: Formulation and Evaluations against Advanced and Metastatic Melanoma.

Fisetin (Fis), a natural flavonoid with anticancer effects, suffers from delivery constraints. Fisetin-nanostructured lipid carriers (NLCs) were developed for better efficacy against metastatic melanoma, employing the design of experiment (DoE) approach. The optimized NLCs depict a particle diameter of 135.0 ± 5.5 nm, a polydispersity index (PDI) of 0.176 ± 0.035, and an entrapment efficiency of 78.16 ± 1.58%. The formulation was stable over a period of 60 days and demonstrated sustained release of the drug (74.79 ± 3.75%) over 96 h. Fis-NLCs depicted at least ∼3.2 times lower IC50 value and ∼1.8 times higher drug uptake at 48 h in A-375 and B16F10 cells compared to that of Fis. It also inhibited the mobility of melanoma cells and induced cell cycle arrest at the G1/S phase. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot results show enhanced expression of Nrf2/NQO1 genes and an apoptotic effect by the upregulation of BAX mRNA expression. The protein levels of BAX and p53 were ∼2-fold higher compared with that of pure Fis. In-vivo studies demonstrated 5.9- and 10.7-fold higher inhibition in melanoma-associated metastasis in the lungs and liver, respectively. The outcomes from this study demonstrated Fis-NLCs as an effective tool against melanoma.

Novel Gels: An Emerging Approach for Delivering of Therapeutic Molecules and Recent Trends.

Gels are semisolid, homogeneous systems with continuous or discrete therapeutic molecules in a suitable lipophilic or hydrophilic three-dimensional network base. Innovative gel systems possess multipurpose applications in cosmetics, food, pharmaceuticals, biotechnology, and so forth. Formulating a gel-based delivery system is simple and the delivery system enables the release of loaded therapeutic molecules. Furthermore, it facilitates the delivery of molecules via various routes as these gel-based systems offer proximal surface contact between a loaded therapeutic molecule and an absorption site. In the past decade, researchers have potentially explored and established a significant understanding of gel-based delivery systems for drug delivery. Subsequently, they have enabled the prospects of developing novel gel-based systems that illicit drug release by specific biological or external stimuli, such as temperature, pH, enzymes, ultrasound, antigens, etc. These systems are considered smart gels for their broad applications. This review reflects the significant role of advanced gel-based delivery systems for various therapeutic benefits. This detailed discussion is focused on strategies for the formulation of different novel gel-based systems, as well as it highlights the current research trends of these systems and patented technologies.

Design and evaluation of cabazitaxel loaded NLCs against breast cancer cell lines.

Cabazitaxel (CBZ) is a taxane derivative and an anti-microtubule agent effective against numerous cancers including drug-resistant cancers. In this study, CBZ loaded nanostructured lipid carriers (NLCs) were prepared by using Design-Expert (DoE) and optimized for various formulation parameters (ratio of lipids and surfactant concentration, homogenization speed and time). The optimized CBZ loaded NLCs formulation was characterized and evaluated through multiple physicochemical characterization techniques like FTIR, DSC, PXRD, SEM and in-vitro drug release. FTIR and DSC results suggested that NLCs entrapped drug inside and had no chemical bonding between drug and NLCs. SEM analysis confirmed homogeneous, spherical, and uniformly distributed NLCs. In-vitro cell culture studies suggested that CBZ loaded NLCs produced ∼ 6- and 2.5-times higher cytotoxicity against MDA-MB-468 and MCF-7 cell lines, respectively compared to pure drug. Cellular uptake of NLC was ∼2.5 and 2.1-fold higher than CBZ alone in MDA-MB-468 and MCF-7 cell lines, respectively. Furthermore, CBZ loaded NLCs produced significantly higher apoptosis and inhibited the mobility of MDA-MB-468 and MCF-7 cells. The results from this study demonstrate the utility of CBZ loaded NLCs as an effective treatment against breast cancer and NLCs as effective drug carriers to deliver the highly lipophilic drug such as CBZ.

A review of nanotechnology-based approaches for breast cancer and triple-negative breast cancer.

Breast cancer (BC) is one of the most prevalent cancers in women. Triple-negative breast cancer (TNBC) in which the three major receptors i.e. estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), are absent is known to express the most aggressive phenotype and increased metastasis which results in the development of resistance to chemotherapy. It offers various therapeutic advantages in treating BC and TNBC. Nanotechnology offers various unique characteristics such as small size (nanometric), active and passive targeting, and the ability to attach multiple targeting moieties, controlled release, and site-specific targeting. This review focuses on conventional drug therapies, recent treatment strategies, and unique therapeutic approaches available for BC and TNBC. The role of breast cancer stem cells in the recurrence of BC and TNBC has also been highlighted. Several chemotherapeutic agents delivered using nanocarriers such as polymeric nanoparticles/micelles, metallic/inorganic NPs, and lipid-based NPs (Liposome, solid-lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs)), etc. with excellent responses in the treatment of BC/TNBC along with breast cancer stem cells have been discussed in details. Moreover, the application of nanomedicine including CRISPR nanoparticle, exosomes for the treatment of BC/TNBC and other molecular targets available such as poly (ADP-ribose) polymerase (PARP), epidermal growth factor receptor (EGFR), Vascular endothelial growth factor (VEGF), etc. for further exploration have also been discussed.