Sumit Kumar

Non‐ionic Dendronized Multiamphiphilic Polymers as Nanocarriers for Biomedical Applications

A new class of non-ionic dendronized multiamphiphilic polymers is prepared from a biodegradable (AB)n-type diblock polymer synthesized from 2-azido-1,3-propanediol (azido glycerol) and polyethylene glycol (PEG)-600 diethylester using Novozym-435 (Candida antarctica lipase) as a biocatalyst, following a well-established biocatalytic route. These polymers are functionalized with dendritic polyglycerols (G1 and G2) and octadecyl chains in different functionalization levels via click chemistry to generate dendronized multiamphiphilic polymers. Surface tension measurements and dynamic light scattering studies reveal that all of the multiamphiphilic polymers spontaneously self-assemble in aqueous solution. Cryogenic transmission electron microscopy further proves the formation of multiamphiphiles towards monodisperse spherical micelles of about 7-9 nm in diameter. The evidence from UV-vis and fluorescence spectroscopy suggests the effective solubilization of hydrophobic guests like pyrene and 1-anilinonaphthalene-8-sulfonic acid within the hydrophobic core of the micelles. These results demonstrate the potential of these dendronized multiamphiphilic polymers for the development of prospective drug delivery systems for the solubilization of poorly water soluble drugs.

A bifunctional nanocarrier based on amphiphilic hyperbranched polyglycerol derivatives

We here report on the synthesis of a bifunctional nanocarrier system based on amphiphilic hyperbranched polyglycerol (hPG), which is modified by introducing hydrophobic aromatic groups to the core and retaining hydrophilic groups in the shell. Selective chemical differentiation and chemo-enzymatic reaction strategies were used to synthesize this new core-shell type nanocarrier. The system shows an innovative bifunctional carrier capacity with both polymeric and unimolecular micelle-like transport properties. Hydrophobic guest molecules such as pyrene were encapsulated into the hydrophobic core of modified hPG via hydrophobic interactions as well as π-π stacking, analogous to a unimolecular micelle system. A second guest molecule, which has a high affinity to the shell like nile red, was solubilized in the outer shell of the host molecule, thus connecting the nanocarrier molecules to form aggregates. This model is confirmed by UV-Vis, fluorescence, atomic force microscopy, and dynamic light scattering, as well as release studies triggered by pH-changes and enzymes. Encapsulated guest molecules, respectively in the core and in the shell, present different controlled release profiles. The bifunctional nanocarrier system is a promising candidate for simultaneous delivery of different hydrophobic drugs for a combination therapy, e.g., in tumor treatment.

Tolerogenic Modulation of the Immune Response by Oligoglycerol– and Polyglycerol–Peptide Conjugates

Peptide-based therapy is a promising strategy for antigen-specific immunosuppression to treat or even heal autoimmune diseases with significantly reduced adverse effects compared to conventional therapies. However, there has been no major success due to the drawbacks of native peptides, i.e., limited bioavailability. Considering the importance and limitations of peptide-based therapies for treatment of autoimmune diseases, we designed and constructed oligoglycerol (OG)- and polyglycerol (PG)-based peptide conjugates. They were evaluated for their biological activity (in vitro and in vivo), bioavailability, and tolerogenic potential. Among the OG- and PG-peptide constructs, PG-peptide constructs exhibited an extended bioavailability compared to OG-peptide constructs and unconjugated peptide. Interestingly, size, structure, and linker chemistry played a critical role for the tolerogenic capacity of the constructs. The PG-peptide construct bound via an ester linkage was the most tolerogenic conjugate, while the PG-peptide construct bound via an amide induced stronger proliferation, but also higher TNF production and lower frequencies of Foxp3(+) regulatory T-cells. Therefore, we conclude that PG-peptide conjugates bound via an ester linkage are not only promising candidates for tolerogenic vaccination, but also open a new avenue toward the application of peptides for the treatment of autoimmune diseases.

Introducing Chirality into Nonionic Dendritic Amphiphiles and Studying Their Supramolecular Assembly

Chiral head groups have been introduced into water-soluble hydroxyl-terminated nonionic amphiphiles and the impact of the head group stereochemistry on the supramolecular ultrastructures has been studied. Enantiomeric isomers were compared with the achiral meso form and the racemic mixture by means of cryogenic transmission electron microscopy and circular dichroism spectroscopy. Structurally, all amphiphiles are composed of the first-generation hydrophilic polyglycerol head group coupled to a single hydrophobic hexadecyl chain through an amide linkage and diaromatic spacer. The enantiomers aggregate to form twisted ribbons with uniform handedness, whereas the meso stereoisomer and racemic mixture produce elongated assemblies, namely, tubules and platelets, but without a chiral ultrastructure. Simulations on the molecular packing geometries of the stereoisomers indicate different preferential assembly routes that explain the individual supramolecular aggregation behavior.

Synthesis of biodegradable amphiphilic nanocarriers by chemo-enzymatic transformations for the solubilization of hydrophobic compounds.

Polymeric nanocarriers possess advanced physicochemical properties that improve bioavailability, enhance cellular dynamics, and control target ability in drug delivery. In particular, dendritic polyglycerol is a promising new biocompatible scaffold for drug delivery. The present study explores the chemo-enzymatic modifications on dendritic hyperbranched polyglycerol (dPG) leading to amphiphilic polymeric architectures with easily hydrolysable ester linkages. Furthermore, these architectures were studied for nile red solubilization with capacity up to 5.6 mg/L at 0.1 wt % polymer conc. This corresponds to an ~10 fold increase in solubility of nile red. The release of nile red from these polymers was observed with a half life of 8 hours at pH 5.0, while no release was found at pH 7.4. The cell viability studies of our polymeric architectures showed them to be relatively nontoxic and to have the potential for future drug delivery applications.

Experimental and theoretical approach to exploit the corrosion inhibition activity of 3-formyl chromone derivatives on mild steel in 1 m H2SO4

Abstract 3-Formyl chromone (3FC) derivatives, viz. 5-methoxy-3FC (5-Me-3FC), 6-hydroxy-3FC (6-OH-3FC), and 7-hydroxy-3FC (7-OH-3FC), were studied for the inhibition of mild steel corrosion in 1 m H2SO4 at different temperatures and concentrations. The inhibition was studied using mass loss method, polarization technique, electrochemical impedance spectroscopy (EIS), scanning electron microscopy, and quantum chemical calculations. The results from mass loss, potentiodynamic polarization, and EIS showed that inhibition efficiency (IE) increased with gradual increments in concentration of 3FC derivatives. The polarization study revealed that these compounds act as mixed-type inhibitors and Langmuir adsorption isotherm is fitted well for adsorption behavior. The order of IE provided by all the three compounds is 7-OH-3FC≈6-OH-3FC>5-Me-3FC and lies in the range of 85%–95%. A proposed inhibition mechanism has been further described, including the support from all the experimental and theoretical techniques.