Development of docetaxel-loaded PEG–PLA nanoparticles using surfactant-free method for controlled release studies

<p>Docetaxel (DTX)-loaded poly(ethylene glycol)–poly(D,L-lactide) is prepared by nanoprecipitation method in the absence of any surfactants. The average particle size of the copolymer was found to be 101 nm. The drug entrapment efficiency (%) and drug loading (%) of polymer were found to be 9.471 ± 0.047 and 94.71 ± 0.466, respectively. The <i>in vitro</i> drug release characteristics show the controlled release of 98% of docetaxel in 72 h. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis measured in terms of cleaved Poly(ADP-ribose) Polymerase (PARP) and cleaved caspase-3 protein expression shows that the copolymer has better cytotoxicity effect and apoptosis in comparison to free DTX in HeLa cells.</p

An Alternatively Packed Dry Molten Globule-like Intermediate in the Native State Ensemble of a Multidomain Protein

It has been difficult to quantify the degree of side-chain conformational heterogeneity in the native (N) state ensemble of proteins and the relative energetic contributions of the side-chain packing and the hydrophobic effect in protein stability. Here, we show using multiple site-specific spectroscopic probes and tools of thermodynamics that the N state ensemble of a multidomain protein contains an equilibrium intermediate (I) whose interdomain region resembles a dry molten globule. In the I state, a tryptophan residue in the interdomain region is alternatively packed, but its secondary structure and intradomain packing are N-like. The I state also has a larger interdomain distance, but the domain–domain interface is dry and molten. Our results indicate that hydrophobic desolvation and side-chain packing are decoupled during protein folding and that interdomain packing interactions have an important energetic contribution in protein stability. Dynamic interconversion between alternatively packed N-like states could be important for multiple allosteric and ligand binding functions of this protein

Evidence for Dry Molten Globule-Like Domains in the pH-Induced Equilibrium Folding Intermediate of a Multidomain Protein

The role of van der Waals (vdW) packing interactions compared to the hydrophobic effect in stabilizing the functional structure of proteins is poorly understood. Here we show, using fluorescence resonance energy transfer, dynamic fluorescence quenching, red-edge excitation shift, and near- and far-UV circular dichroism, that the pH-induced structural perturbation of a multidomain protein leads to the formation of a state in which two out of the three domains have characteristics of dry molten globules, that is, the domains are expanded compared to the native protein with disrupted packing interactions but have dry cores. We quantitatively estimate the energetic contribution of vdW interactions and show that they play an important role in the stability of the native state and cooperativity of its structural transition, in addition to the hydrophobic effect. Our results also indicate that during the pH-induced unfolding, side-chain unlocking and hydrophobic solvation occur in two distinct steps and not in a concerted manner, as commonly believed

Rural-urban transition and the peri-urban sanitation gap: evidence from Hyderabad, India

This record includes an extended abstract and MP4 presentation. Presented at the 42nd WEDC International Conference

The circular economy for sanitation: a study of five cases in India

This record includes an extended abstract and MP4 presentation. Presented at the 42nd WEDC International Conference