Syed Zajif Hussain

Protein-mediated synthesis, pH-induced reversible agglomeration, toxicity and cellular interaction of silver nanoparticles

Casein, a milk protein, is used to produce biotolerable and highly stable silver nanoparticles with a fair control over their size without using any additional reducing agent. These silver nanoparticles undergo reversible agglomeration to form protein-silver nanoparticle composite agglomerates as pH approaches to the isoelectric point of casein protein (pI=4.6). These agglomerates can then easily be re-dispersed in alkaline aqueous media with no obvious change in their optical properties. The nanoparticles can withstand high salt concentration (~0.5M), and can also be freeze-dried, stored as dry powder and then dispersed in aqueous media whenever required. More interestingly, by controlling the concentration of casein protein and pH, it was also possible to control the self-assembly of silver nanoparticles to produce fairly uniform spherical agglomerates. The nanoparticles and their agglomerates were thoroughly characterized using UV-visible and FTIR spectroscopy, TEM, SEM and DLS, etc. Cytotoxicity of the hybrid materials was examined using a Resazurin based cytotoxicity assay. After determining the LD(50) using NIH/3T3 fibroblast cells, the cellular interaction of these hybrid nanoparticles was studied to examine the behavior of casein-coated nanoparticles for their potential bio-applications.

Synthesis, characterization and evaluation of lecithin-based nanocarriers for the enhanced pharmacological and oral pharmacokinetic profile of amphotericin B

We report the synthesis, characterization and evaluation of lecithin-drug hybrid nanocarriers (NCs) with enhanced oral bioavailability and anti-parasitic potential for poorly water-soluble drugs. Amphotericin B (AmB), a poor water-soluble drug with poor membrane penetrating ability, was selected as a model drug to demonstrate the potential of the lecithin-drug hybrid NCs. Lec-AmB NCs were prepared by the self-assembly of lecithin into nanoparticles (NPs) at a critical micellar concentration of 4 mg ml-1 and into liposomes at a critical liposomal concentration of 53 mg ml-1 in aqueous systems. The Lec-AmB NPs (200-300 nm) were further coated with polyethylene glycol (MW 600) and Tween 20, whereas the liposomes (70-90 nm) were used as such for this study. The Lec-AmB NCs were evaluated for their ability to boost in vivo oral pharmacokinetic parameters in rabbits and in vitro anti-leishmanial activity against the promastigotes of Leishmania tropica. A reciprocal relationship was observed between the size and drug encapsulation efficiency of the NPs, but no such relationship was observed in the case of the liposomes. More importantly, the oral bioavailability and anti-leishmanial activity of Lec-AmB NPs was enhanced up to 21- and 6.3-fold, and 21- and 2-fold, respectively, in the case of the liposomes. The improvement in the bioavailability and anti-leishmanial activity is very significant compared to the deoxycholate complex of AmB (water soluble, injectable market product: Anfotericina FADA®), and this study, thus shows the promising potential of easy-to-prepare NCs with improved therapeutic efficiency using phosphocholine-based biocompatible surfactants.

Fabrication of superhydrophobic filter paper and foam for oil–water separation based on silica nanoparticles from sodium silicate

We demonstrate the synthesis of hydrophobic silica nanoparticles from sodium silicate and their application in separation of the oil–water mixture. For this, hydrophobic silica nanoparticles of size 35 ± 8 nm were initially synthesized by sol–gel method using sodium silicate and trimethylchlorosilane, and further deposited on commercially available filter paper and polyurethane foam by dip coating technique. The coating cycles were optimized for filter paper to ensure that fibers of the filter paper have been completely covered with hydrophobic silica nanoparticles to provide an ideal porous superhydrophobic/superoleophilic framework for gravity based separation of oil–water mixtures. It was confirmed by water contact angle of ~155° and sliding angle <5°. Whereas the superhydrophobic polyurethane foam was utilized for collection of oil from oil–water mixtures via absorption. The capability of these materials to separate oil from water was tested against the mixtures of water with n-hexane, gasoline, diesel, kerosene oil and engine oil. Moreover, the produced particles can also be used for fabrication of semi-transparent superhydrophobic surfaces.Graphical Abstract

Folate grafted thiolated chitosan enveloped nanoliposomes with enhanced oral bioavailability and anticancer activity of docetaxel

Folate grafted and thiolated chitosan was synthesized and wrapped on the surface of mixed phosphatidylcholine based nanoliposomes (NLs) to improve the oral absorption and targeted pharmacological activity of anti-cancer drugs against breast cancer. In this study, a chitosan derived thiomer, having intrinsic properties of P-glycoprotein (P-gp) efflux pump inhibition, mucoadhesion and controlled drug release at a target site, was exploited to improve the performance of docetaxel (DTX) loaded NLs for better oral pharmacokinetics, targeted anti-cancer activity, liposomal stability and the physical characteristics of NLs. Thiomer enveloped nanoliposomes (ENLs) and bare nanoliposomes (NLs) were synthesized with the ingredient ratio pre-determined via Response Surface Methodology (RSM) plots by Design Expert® software. ENLs and NLs were thoroughly characterized for their surface chemistry, particle size, zeta potential, PDI, encapsulation efficiency, stability and release profile. ENLs were spherical in shape with a particle size of 328.5 ± 30 nm, a positive zeta potential of 18.81 ± 2.45 and a high encapsulation efficiency of 83% for DTX. Controlled release of DTX from formulations was observed for over 72 h for each formulation. The presence of thiol groups at the surface of the ENLs resulted in higher swelling and in situ gelling properties compared to the corresponding NLs. Furthermore, ENL/mucin mixtures showed a time dependent increase in viscosity for up to 12 h, leading to a 19.07-fold increased viscosity. Ex vivo permeation and P-glycoprotein inhibiting properties, studied in rats small intestine, showed a 9.6-fold higher permeation and 13-fold enhancement of DTX in the presence of ENLs. In vitro cytotoxicity studies indicated that the ENLs can efficiently kill MD-MB-231 breast cancer cells with 200 fold lower IC50 values than DTX alone as a positive control. The pharmacokinetic study revealed that the ENLs significantly improved the oral bioavailability of DTX i.e. up to 13.6 fold as compared to an aqueous dispersion of DTX. Therefore, these enveloped hybrid nanoliposomes (ENLs) have the potential to be developed as useful nanocarriers for efficient oral delivery and breast cancer management using DTX.

Lecithin-gold hybrid nanocarriers as efficient and pH selective vehicles for oral delivery of diacerein—In-vitro and in-vivo study

We report the synthesis and evaluation of lecithin-gold hybrid nanocarriers for the oral delivery of drugs with improved pharmacokinetics, Au-drug interactive bioactivity and controlled drug releasing behavior at physiological pH inside human body. For this purpose, diacerein, a hydrophobic anti-arthritic drug, was loaded in lecithin NPs (LD NPs), which were further coated by Au NPs either by in-situ production of Au NPs on LD NPs or by employing pre-synthesized Au NPs. All LDAu NPs were found to release drug selectively at the physiological pH of 7.4 and showed 2.5 times increase in the oral bioavailability of diacerein. Pharmacological efficacy was significantly improved i.e., greater than the additive effect of diacerein and Au NPs alone. LDAu NPs started suppressing inflammation at first phase, whereas LD NPs showed activity in the second phase of inflammation. These results indicate the interaction of Au NPs with prostaglandins and histaminic mediators of first phase of carrageenan induced inflammation. Acute toxicity study showed no hepatic damage but the renal toxicity parameters were close to the upper safety limits. Toxicity parameters were dependent on surface engineering of LDAu NPs. Apart from enhancing the oral bioavailability of hydrophobic drugs and improving their anti-inflammatory activity, these hybrid nanocarriers may have potential applications in gold-based photothermal therapy and the tracing of inflammation at atherosclerotic and arthritic site.

Design, characterization and evaluation of hydroxyethylcellulose based novel regenerable supersorbent for heavy metal ions uptake and competitive adsorption

Hydroxyethylcellulose succinate-Na (HEC-Suc-Na) was designed and evaluated for removal of some heavy metal ions from aqueous solution. Pristine sorbent HEC-Suc-Na was thoroughly characterized by FTIR and solid-state CP/MAS 13C NMR spectroscopy, SEM-EDS and zero point charge analyses. Langmuir isotherm, pseudo second order kinetic and ion exchange models provided best fit to the experimental data of sorption of metal ions. Maximum sorption capacities of supersorbent HEC-Suc-Na for sorption of heavy metal ions from aqueous solution as calculated by Langmuir isotherm model were found to be 1000, 909.09, 666.6, 588 and 500mgg-1 for Pb(II), Cr(VI), Co(II), Cu(II) and Ni(II), respectively. Competitive sorption of these heavy metal ions was carried out from galvanic and nuclear waste water simulated environment. The negative values of ΔG° and ΔH° indicated spontaneity and exothermic nature of sorption. The sorbent was efficiently regenerated with no significant decrease in sorption capacity after five cycles.

Design and Utility of Metal/Metal Oxide Nanoparticles Mediated by Thioether End-Functionalized Polymeric Ligands

The past few decades have witnessed significant advances in the development of functionalized metal/metal oxide nanoparticles including those of inorganic noble metals and magnetic materials stabilized by various polymeric ligands. Recent applications of such functionalized nanoparticles, including those in bio-imaging, sensing, catalysis, drug delivery, and other biomedical applications have triggered the need for their facile and reproducible preparation with a better control over their size, shape, and surface chemistry. In this perspective, the multidentate polymer ligands containing functional groups like thiol, thioether, and ester are important surface ligands for designing and synthesizing stable nanoparticles (NPs) of metals or their oxides with reproducibility and high yield. These ligands have offered an unprecedented control over the particle size of both nanoparticles and nanoclusters with enhanced colloidal stability, having tunable solubility in aqueous and organic media, and tunable optical, magnetic, and fluorescent properties. This review summarizes the synthetic methodologies and stability of nanoparticles and fluorescent nanoclusters of metals (Au, Ag, Cu, Pt, and other transition metal oxides) prepared by using thioether based ligands and highlights their applications in bio-imaging, sensing, drug delivery, magnetic resonance imaging (MRI), and catalysis. The future applications of fluorescent metal NPs like thermal gradient optical imaging, single molecule optoelectronics, sensors, and optical components of the detector are also envisaged.

A superporous and superabsorbent glucuronoxylan hydrogel from quince (Cydonia oblanga): Stimuli responsive swelling, on-off switching and drug release.

Current study was designed to investigate micromeritic properties, water absorption capacity, stimuli (pH, ethanol and saline) responsive swelling-deswelling (on-off switching) and controlled drug release from the polysaccharide glucuronoxylan isolated from the seeds of Quince. The water retention capacity of Quince hydrogel (QH) was found admirable. The hydrogel also exhibited privileged swelling in water and basic buffers (pH 6.8 and 7.4) while insignificant swelling in acidic buffer (pH 1.2). The swelling kinetics of QH follows second order. Moreover, QH deswells in salt (KCl and NaCl) solutions and ethanol. SEM of swollen then freeze dried QH revealed hollow channels with an average diameter of 67.8μm. Furthermore, QH sustained the release of levosulpiride (LS) tablet formulation and drug release mechanism was ascertained super case-II transport. These results signify QH a smart material for sustained release formulations.

Polysaccharide based superabsorbent hydrogel from Mimosa pudica: swelling–deswelling and drug release

Herein, we have evaluated a polysaccharide, glucuronoxylan, isolated from the seeds of Mimosa pudica (MP) for its water holding capacity, pH and salt responsive swelling–deswelling behavior, and sustained drug release. The MP hydrogel (MPH) has shown a high water retention capacity. The MPH exhibited negligible swelling at pH 1.2 while high swelling was observed at pH 6.8, 7.4 and in deionized water which follows second order kinetics, whereas the MPH deswells in NaCl and KCl solutions and ethanol. The presence of interconnected macropores with an average diameter of 62.94 μm was revealed using scanning electron microscopy (SEM) of a swollen then freeze dried sample of MPH. Furthermore, the MPH was explored as a sustained release material for a tablet formulation of diclofenac sodium. The drug release mechanism from the MPH containing tablet formulation was found to be super case-II transport. The results have indicated that the MPH could be a potential candidate for sustained release formulations.

Catalysis by multifunctional polyelectrolyte capsules

Gold nanoparticles and nanocomposites have high catalytic performance for several chemical reactions. Here we present gold and iron oxide nanoparticle modified polymer capsules as porous and multifunctional platforms for catalysis. Layer-by-layer polyelectrolyte microcapsules were formed on calcium carbonate template cores loaded with gold nanoparticles, allowing for high gold loading of the capsules. Magnetic nanoparticles were incorporated in the polymeric shells of the capsules, allowing for magnetic separation. The influence on the catalytic behaviour of gold was studied in terms of the nanoparticle size, the presence of a polymeric shell, and the presence of the magnetic nanoparticles in the shell, by using the model electron transfer reaction between hexacyanoferrate(III) and borohydride.