Reactive Pt(II) center as part of redox-active quinoline-based heterocyclic scaffolds toward new anticancer leads.

New cisplatin analogs in which the diamminedichloro-Pt(II) unit is conjugated to dihydroquinoline- or tetrahydroquinoline frameworks were synthesized and subjected to biological evaluation in order to understand their effects on cellular redox homeostasis and cell viability. They exhibited better selectivity towards cancer cells (A549) compared to mice fibroblast NIH3T3 cells, with cytotoxicity in the same range as that of cisplatin. There was structure-dependent variation in the levels of ROS and were also able to induce cell death, as evidenced by accumulation of cells in sub-G1 phase.

Functionalizable oxanorbornane-based head-group in the design of new Non-ionic amphiphiles and their drug delivery properties.

A new group of non-ionic amphiphiles with short alkyl chains and functionalizable oxanorbornane-based head group for drug delivery application are presented. They can be prepared through a sequence that starts with cycloaddition of Boc-protected furfuryl amine with maleic anhydride and reduction of the resulting adduct with LiAlH4 to get a diol intermediate. Introduction of alkyl chains through these primary hydroxyl groups and subsequent head-group modification via cis-hydroxylation resulted in a number of new amphiphiles in good yields. They were characterized by various spectro-analytical techniques and then subjected to drug-delivery studies using ibuprofen as a model drug. Functionalization of the head group through the amine functionality was also done with an intention to improve lipid packing to get better drug-loading and release properties. Irrespective of the nature of groups attached through this amine unit, all amphiphiles with short alkyl chains were found to assemble into spherical aggregates when drop-casted from various organic solvents. The same assembly preference prevailed in their formulations containing lipid-cholesterol-drug in 1: 0.5:1 ratio as well, and these particles had diameters <300 nm. Apart from good drug-loading efficiencies, these amphiphiles exhibited controlled release properties and did not show any indication of toxicity when assayed against NIH3T3 cells. The formulation based on lipid having a phenylalanine unit on the head group (1.10c) turned out to be the best in this series which showed a loading efficiency of 57.6% with a controlled release of ~42% by end of 24 h. Because of efficient layering that is facilitated by hydrogen bonding involving well-directed hydroxyl groups on the head group, amphiphiles with alkyl chains as short as C5 are able to act as efficient drug delivery systems, which is one of the highlights of this work.

A modular approach towards drug delivery vehicles using oxanorbornane-based non-ionic amphiphiles.

The self-assembly of non-ionic amphiphiles with a hydroxylated oxanorbornane head-group was controlled using amino acid units as spacers between hydrophilic and lipophilic domains to get spherical supramolecular aggregates. The ability of these systems to harbour therapeutic agents like ibuprofen, and their drug-release profiles were evaluated. Apart from directing the assembly, the intervening amino acid unit was found to help in drug entrapment as well. The presence of cholesterol improved their drug-loading ability, and an encapsulation efficiency of up to 66% was shown by the formulation containing the phenylalanine residue as the spacer (NC1c). There was no burst release, and 45% drug release was observed at the end of 24 h in this case (cf. soyaphosphatidylcholine based formulation = 49%). The results from SEM, Cryo-TEM, PXRD and confocal microscopic studies with some insights into molecular packing in this class of aggregates are also included.

Synthesis, characterization and biological activities of curcumin nanospheres.

Curcumin is one of the most versatile compounds obtained from Curcuma longa. The major obstacle in the therapeutic use of curcumin is its aqueous solubility. To enhance its aqueous solubility and biological activities, we prepared curcumin nanospheres (CNSs) by wet milling-solvent evaporation technique without any surfactants. In this study, we have focused on the synthesis, characterization and biological effects of CNSs. DLS and SEM analyses showed 50-80 nm spherical shaped CNSs with a zeta potential of -31.65 mV. FTIR revealed that there were no structural changes to CNSs. Antibacterial and antifungal studies proved that CNSs were much more effective than curcumin against Escherichia coil, Staphylococcus aureus and Candida albicans. Antioxidant activity of CNSs showed promising result for therapeutic applications. The in vitro anti-inflammatory studies proved that CNSs possessed enhanced anti-inflammatory effect against protein denaturation. Cytotoxicity and uptake of CNSs showed more toxicity on cancer cells (T47D, MG63, A375) sparing normal HDF and IEC cell lines. Skin permeation studies showed CNSs retained at different layers of pig skin. These results give clear evidence for their use against microbial and fungal skin infections as well as cancer treatment.