Theranostic lyotropic liquid crystalline nanostructures for selective breast cancer imaging and therapy.

Herein, we report the development of theranostic lyotropic liquid crystalline nanostructures (LCN's) loaded with unique MnO nanoparticles (MNPs) for selective cancer imaging and therapy. MNPs serves as a fluorescent agent as well as a source of manganese (Mn2+) and enables localized oxidative stress under the hallmarks of cancer (acidosis, high H2O2 level). In pursuit of synergistic amplification of Mn2+ antitumor activity, betulinic acid (BA) is loaded in LCN's. In this investigation, nano-architecture of LCN's phase interface is established via SAXS, Cryo-TEM and Cryo-FESEM. Intriguing in vitro studies showed that the LCN's triggered hydroxyl radical production and exhibited greater selective cytotoxicity in cancer cells, ensuring the safety of normal cells. Significant tumor ablation is realized by the 96.5 % of tumor growth inhibition index of LCN's as compared to control group. Key insights into on-site drug release, local anti-cancer response, and tumor location are gained through precise guidance of fluorescent MNPs. In addition, comprehensive assessment of the safety, pharmacokinetics and tumor distribution behavior of LCN's is performed in vivo or ex vivo. This work emphasizes the promise of modulating tumor microenvironment with smart endogenous stimuli sensitive nano systems to achieve advanced comprehensive cancer nano-theranostics without any external stimulus. STATEMENT OF SIGNIFICANCE: Effective diagnosis and treatment approaches with maximum anti-cancer activity and minimal side-effects are critical to ameliorate cancer therapy. Compared to radiation, photodynamic and photothermal therapy, the specific and selective activation of tumor microenvironmental endogenous stimuli for the logical generation of cytotoxic OH· free radicals serves as an efficient therapeutic strategy for chemodynamic-cancer treatment. In this investigation, MnO nanoparticles fulfill two needs (fluorescence-based optical imaging and a source of Mn2+ based chemodynamic therapy) in one unit. This approach also ensures the safety of normal cells, as the toxic OH· free radical activity is substantially suppressed under the mild alkaline/H2O2 conditions in normal cell microenvironment.

P-gp modulatory acetyl-11-keto-ß-boswellic acid based nanoemulsified carrier system for augmented oral chemotherapy of docetaxel.

In spite of being a very potent and promising drug against many types of cancer, docetaxel suffers the disadvantage of low solubility and poor bioavailability rendering it unsuitable for oral administration. Also, the available marketed formulation for intravenous administration has its inherent drawbacks owing to the presence of polysorbate 80. Here, we exploited the anticancer and P-gp inhibitory potential of naturally occurring frankincense oil to fabricate a stable docetaxel loaded nanoemulsified carrier system for oral delivery. The nanoemulsion possessing desirable particle size (122±12nm), polydispersity (0.086±0.007) and zeta potential (-29.8±2.1mV) was stable against all type of physical stresses and simulated physiological conditions tested. The formulation showed higher uptake in Caco-2 cells and inhibited P-gp transporter significantly (P<0.05). In MDA-MB-231 cells, it showed less IC50, arrested cells in G2-M phase and exhibited higher degree of apoptosis than marketed formulation Taxotere®. The 182.58±4.16% increment in relative oral bioavailability led to higher in vivo anti-proliferative activity manifesting 19% more inhibition than Taxotere®. Conclusively, it is revealed that the developed nanoemulsion will be a propitious approach towards alternative docetaxel therapy.

Dual functioning microspheres embedded crosslinked gelatin cryogels for therapeutic intervention in osteomyelitis and associated bone loss.

In the present research,we simultaneously addressed the condition of osteomyelitis and osteoporosis by developing a gelatin based chemically cross linked cryogel system embedded with CaCO3 microspheres and ciprofloxacin hydrochloride was incorporated in both the microspheres and the 3D matrix of cryogel. The fabricated cryogel was characterized for the swelling ratio, swelling kinetics, porosity, pore volume, compression strength and in vitro rate of degradation which were found to be dependent on the concentration of gelatin, duration of freezing and number of freeze-thaw cycles. The sustained release of drug was obtained up to 21days after the initial burst, and the concentration was maintained above the MIC for the entire duration of the study. The in vitro antibacterial study in Staphylococcus aureus and Escherichia coli exhibited 33mm, 30mm, 28mm, 27mm and 43mm, 37mm, 37mm, and 36mm zone of inhibition respectively at day 1, 3, 5 and 7. The cell viability, number of cells in the growth phase and alkaline phosphatase levels were found to be significantly higher in rat osteoblasts cultured in cryogel as compared to 2D surface. All these results demonstrate the propitious potential of this microsphere incorporated, ciprofloxacin-loaded, industrially scalable cryogel system for therapeutic intervention in osteoporosis and associated osteomyelitis.