Garcinol (GAR) is a naturally occurring polyisoprenylated phenolic compound. It has been recently investigated for its biological activities such as antioxidant, anti-inflammatory, anti ulcer, and antiproliferative effect on a wide range of human cancer cell lines. Though the outcomes are very promising, its extreme insolubility in water remains the main obstacle for its clinical application. Herein we report the formulation of GAR entrapped PLGA nanoparticles by nanoprecipitation method using vitamin E TPGS as an emulsifier. The nanoparticles were characterized for size, surface morphology, surface charge, encapsulation efficiency and in vitro drug release kinetics. The MTT assay depicted a high amount of cytotoxicity of GAR-NPs in B16F10, HepG2 and KB cells. A considerable amount of cell apoptosis was observed in B16f10 and KB cell lines. In vivo cellular uptake of fluorescent NPs on B16F10 cells was also investigated. Finally the GAR loaded NPs were radiolabeled with technetium-99m with >95% labeling efficiency and administered to B16F10 melanoma tumor bearing mice to investigate the in vivo deposition at the tumor site by biodistribution and scintigraphic imaging study. In vitro cellular uptake studies and biological evaluation confirm the efficacy of the formulation for cancer treatment.

Aim: Chitosan-coated polylactic-co-glycolic acid nanoparticles of voriconazole (VChNP) were developed to increase residence time and provide sustained drug release locally to treat recurrent lung-fungal infection. Materials & methods: VChNP has been developed using a simple, unique technique and characterized. Pharmacokinetics, lung deposition with time and gamma imaging were conducted with optimized formulations. Results: The deposition of fluorescein isothiocyanate-labeled VChNP in lung was confirmed by confocal microscopy. Gamma-scintigraphic images showed that Tc-99m-labeled VChNP had better pulmonary retention for longer period than that of noncoated formulation. Drastic improvement in pharmacokinetic profile of VChNP than noncoated formulation was observed. Conclusion: Thus, VChNP may be useful for effective pulmonary delivery with improved bioavailability. Such chitosan-coated nanoparticles may open up a new avenue for efficacious treatment of lung-fungal infection. Graphical abstract

Delivering highly water soluble drugs across blood–brain barrier (BBB) is a crucial challenge for the formulation scientists. A successful therapeutic intervention by developing a suitable drug delivery system may revolutionize treatment across BBB. Efforts were given here to unravel the capability of a newly developed fatty acid combination (stearic acid:oleic acid:palmitic acid = 8.08:4.13:1) (ML) as fundamental component of nanocarrier to deliver highly water soluble zidovudine (AZT) as a model drug into brain across BBB. A comparison was made with an experimentally developed standard phospholipid-based nanocarrier containing AZT. Both the formulations had nanosize spherical unilamellar vesicular structure with highly negative zeta potential along with sustained drug release profiles. Gamma scintigraphic images showed both the radiolabeled formulations successfully crossed BBB, but longer retention in brain was observed for ML-based formulation (MGF) as compared to soya lecithin (SL)-based drug carrier (SYF). Plasma and brain pharmacokinetic data showed less clearance, prolonged residence time, more bioavailability and sustained release of AZT from MGF in rats compared to those data of the rats treated with SYF/AZT suspension. Thus, ML may be utilized to successfully develop drug nanocarrier to deliver drug into brain across BBB, in a sustained manner for a prolong period of time and may provide an effective therapeutic strategy for many diseases of brain. Further, many anti-HIV drugs cannot cross BBB sufficiently. Hence, the developed formulation may be a suitable option to carry those drugs into brain for better therapeutic management of HIV.

The cytotoxic drug gemcitabine (GEM) has been conjugated to receptor-binding peptides to target melanoma tumors. A hexapeptide having a Lys–Gly–His–Lys sequence (pep-1), an octapeptide with an Arg–Gly–Asp–Lys–Gly–His–Lys sequence (pep-2), a GEM-conjugated Lys–Gly–His–Lys peptide (GEM–pep-3) and a GEM-conjugated Asp–Gly–Arg peptide (GEM–pep-4) were synthesized and characterized. In vitro uptake of fluorescently labeled GEM–pep-3 and GEM–pep-4 on B16F10 cells was investigated. Fluorescence microscopy studies demonstrated significant uptake of GEM–pep-3 in the B16F10 mouse melanoma cell line. The peptides and GEM-coupled peptides were radiolabeled with [^99mTc(CO)₃(H₂O)₃]⁺ and examined for in vitro cell binding in the B16F10 melanoma cell line and in vivo biodistribution and scintigraphic studies in a B16F10 melanoma tumor-bearing mice model. In vitro cellular uptake studies and biological evaluation confirmed significant deposition of GEM–pep-3 at the melanoma tumor site. The MTT assay depicted higher cytotoxic behaviour of GEM–pep-3 than free GEM. A considerable amount of cell apoptosis was also observed in B16F10 cells. Finally, the in vivo therapeutic efficacy study revealed a significant decrease in tumor growth in the GEM–pep-3-treated animal model. These studies reveal enough potentiality of GEM–pep-3 to treat melanoma and underline the need for further evaluation.