Samarendra Maji

PDMAEMA based gene delivery materials

Gene transfection is the transfer of genetic material like DNA into cells. Cationic polymers which form nanocomplexes with DNA, so-called non-viral gene vectors, are a highly promising platform for efficient gene transfection. Despite intensive research efforts and some of the on-going clinical trials on gene transfection, none of the existing cationic polymer systems are generally acceptable for human gene therapy. Since the process of gene transfection is complex and puts different challenges and demands on the delivery system, there is a strong requirement for the design and development of a multifunctional system in a simple way. This review will discuss recent efforts in design, synthesis, and performance of poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) nanocomplexes with DNA.

Polymer-protein conjugation via a ‘grafting to’ approach – a comparative study of the performance of protein-reactive RAFT chain transfer agents

Efficient polymer-protein conjugation is a crucial step in the design of many therapeutic protein formulations including nanoscopic vaccine formulations, antibody-drug conjugates and to enhance the in vivo behaviour of proteins. Here we aimed at preparing well-defined polymers for conjugation to proteins by reversible addition–fragmentation chain transfer (RAFT) polymerization of both acrylates and methacrylamides with protein-reactive chain transfer agents (CTAs). These RAFT agents contain either a N-hydroxysuccinimide (NHS) or pentafluorophenyl (PFP) ester moiety that can be conjugated to lysine residues, and alternatively a maleimide (MAL) or pyridyl disulfide (PDS) moiety that can be conjugated to cysteine residues. Efficiency of the bioconjugation of these polymers to bovine and avian serum albumin was investigated as a function of stoichiometry, polymer molecular weight and the presence of reducing agents. A large molar excess of polymer was required to obtain an acceptable degree of protein conjugation. However, protein modification with N-succinimidyl-S-acetylthiopropionate (SATP) to introduce sulfhydryl groups onto primary amines, significantly increased conjugation efficiency with MAL- and PDS-containing polymers.

Novel amphiphilic, biodegradable, biocompatible, cross-linkable copolymers: synthesis, characterization and drug delivery applications

The synthesis of a new kind of amphiphilic poly(vinyl-co-ester)s via simple one-pot radical ring-opening polymerization (RROP) is reported. A series of biodegradable, biocompatible, and cross-linkable copolymers P(MDO-co-PEGMA-co-CMA) with different compositions were synthesized by copolymerization of 2-methylene-1,3-dioxepane (MDO), poly(ethylene glycol) methyl ether methacrylate (PEGMA) and 7-(2-methacryloyloxyethoxy)-4-methylcoumarin methacrylate (CMA). All the copolymers were well characterized by 1H NMR, 13C NMR, and gel permeation chromatography (GPC). The hydrolytic degradation and enzymatic degradation of the copolymers were investigated. The amphiphilic P(MDO-co-PEGMA-co-CMA) can self-assemble into micelles in aqueous solution. Polymeric micelles with different sizes were obtained through tuning the compositions of the copolymers, i.e., the hydrophilic/hydrophobic ratio. The size and morphology of the micelles were measured by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Because of the coumarin side groups in the micellar core, the micelles can be cross-linked upon exposure to long-wavelength UV light (λ = 365 nm). These micelles also showed excellent biocompatibility by the in vitro cytotoxicity experiments. Furthermore, the biodegradable micelles were applied for the delivery of an anticancer drug doxorubicin (DOX). The cell viability of DOX-loading micelles compared to free DOX was discussed. The effects of cross-linking and the copolymer composition on the drug release behavior were well studied. The results indicate that this new kind of amphiphilic poly(vinyl-co-ester)s could serve as promising nanocarriers for the delivery of anticancer drugs.

Tuning the LCST and UCST Thermoresponsive Behavior of Poly( N,N -dimethylaminoethyl methacrylate) by Electrostatic Interactions with Trivalent Metal Hexacyano Anions and Copolymerization

Poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) has been reported to show both upper critical solution temperature (UCST) and lower critical solution temperature (LCST) behavior in presence of trivalent metal hexacyano anions, which is attractive for the development of smart materials. In this communication, the influence of the double thermoresponsive behavior of PDMAEMA driven by electrostatic interactions is investigated by comparing systems with [Co(CN)6 ](3-) , [Fe(CN)6 ](3-) , and [Cr(CN)6 ](3-) as trivalent anions. Furthermore, tuning of double thermoresponsive behavior of PDMAEMA by incorporating hydrophilic or hydrophobic comonomers is also discussed in the presence of [Fe(CN)6 ](3-) as trivalent ion.

Poly(N-isopropylacrylamide) coated gold nanoparticles as colourimetric temperature and salt sensors

Thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) coated gold nanoparticles (AuNPs) are reported having residual citrate groups on the surface resulting from their synthesis via the Turkevich method. These PNIPAM coated AuNPs have dual stabilisation by the polymer chains and the charges, which we exploit for the development of temperature and salt sensors of which the sensing regime can be tuned by variation of salt concentration and temperature, respectively.

Hydrogen bonded multilayer films based on poly(2-oxazoline)s and tannic acid

In recent years, the layer-by-layer (LbL) assembly based on hydrogen bonding interactions is gaining popularity for the preparation of thin film coatings, especially for biomedical purposes, based on the use of neutral, non-toxic building blocks. The use of tannic acid (TA) as hydrogen bonding donor is especially interesting as it results in LbL films that are stable under physiological conditions. In this work, investigations on the LbL thin film preparation of TA with poly(2-oxazoline)s with varying hydrophilicity, namely poly(2-methyl-2-oxazoline) (PMeOx), poly(2-ethyl-2-oxazoline) (PEtOx) and poly(2-n-propyl-2-oxazoline) (PnPropOx), are reported. The LbL assembly process is investigated by quartz crystal microbalance and UV-vis spectroscopy revealing linear growth of the film thickness. Furthermore, isothermal titration calorimetry demonstrates the LbL assembly of TA, and PMeOx is found to be mostly enthalpy driven while the LbL assembly of TA with PEtOx and PnPropOx is mostly entropy driven. Finally, scanning electron microscopy and ellipsometry demonstrate the formation of smooth thin films for LbL assembly of TA with all three polymers. Such poly(2-oxazoline) coatings have high potential for use as anti-biofouling coatings.

RAFT polymerization of 4-vinylphenylboronic acid as the basis for micellar sugar sensors

Well-defined homo and mPEGylated block (co)polymers of the commercially available unprotected 4-vinylphenylboronic acid (4-VBA) monomer are reported based on reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymerization kinetics are studied in detail for homo and block (co)polymerizations with different chain transfer agents (CTAs) to optimize the preparation of well-defined polymer structures, eventually leading to comparatively low dispersities (Đ ≤ 1.25). Subsequently, block (co)polymers with methoxy poly(ethylene glycol) mPEG-b-P(4-VBA) are prepared using a mPEG-functionalized CTA. The formed block copolymer mPEG114 -b-P(4-VBA)30 is demonstrated to be pH and glucose responsive as its micellization behavior is dictated by pH as well as the presence of glucose. The glucose-responsive pH window of mPEG114 -b-P(4-VBA)30 is found to be pH 9-10 based on the DLS and TEM measurement.

Thermoresponsive polymer coated gold nanoparticles: from MADIX/RAFT copolymerization of N-vinylpyrrolidone and N-vinylcaprolactam to salt and temperature induced nanoparticle aggregation

In the present contribution, we report the MADIX/RAFT polymerization for the synthesis of thermoresponsive homo and statistical copolymers of N-vinylcaprolactam (NVCL) and N-vinylpyrrolidone (NVP). The conditions for the polymerization of NVP were optimized using an automated parallel synthesizer and these optimal conditions were applied for preparing copolymers with systematical variation in composition. The cloud point temperatures (TCPs) of aqueous solutions of PNVCL and P(NVCL-stat-NVP)’s (CP1–CP5) were found to be tuneable between 40 °C and >95 °C at 5 mg mL−1. Next, stable colloidal solutions of AuNPs coated with PNVCL and CP1–CP5 were obtained via an exchange reaction of pre-synthesized citrate stabilized AuNPs with PNVCL and CP1–CP5 by a direct ‘grafting to’ approach. The maximum absorbance wavelength (λmax) of the surface plasmon resonance (SPR) band and size of all the thermoresponsive polymer coated AuNPs were found to be almost unchanged up to 65 °C (above the TCP of PNVCL and CP5) in MilliQ water which is presumably due to electrostatic stabilization of the AuNPs by residual citrate groups on the surface. However, in 0.1 M NaCl aqueous solution the λmax of the thermoresponsive AuNPs were red shifted when heated up to 65 °C which is attributed to the screening of the citrate negative charges on the surface of AuNPs that suppress electrostatic stabilization enabling T-induced aggregation leading to a shift in the SPR band. These thermoresponsive AuNPs may find applications as colorimetric temperature and/or salt sensors.

Reversible Calcium(II)-Ion Binding through an Apparent pKa Shift of Thermosensitive Block-Copolymer Micelles.

There is an increasing need for smart materials capable of removing multivalent ions from aqueous streams without the inconvenience of brine regeneration as in ion-exchange processes. Herein, we present a thermoresponsive micellar system consisting of polystyrene-poly(methoxy diethyleneglycol acrylate) block copolymer surfactants modified with carboxylic acid end groups (PS-PMDEGA-COOH) that can be used to switch between the adsorption and desorption of divalent calcium(II) cations by a mild temperature trigger, thus providing a new type of thermoregenerable ion-adsorbing materials. The switch of calcium(II)-binding capacity is demonstrated to result from a shift in the pKa value of the carboxylic acid groups by the collapse and redissolution of the PMDEGA block and the associated change in local polarity.

Antimicrobial Hydantoin-grafted Poly(ε-caprolactone) by Ring-opening Polymerization and Click Chemistry

Novel degradable and antibacterial polycaprolactone-based polymers are reported in this work. The polyesters with pendent propargyl groups are successfully prepared by ring-opening polymerization and subsequently used to graft antibacterial hydantoin moieties via click chemistry by a copper(I)-catalyzed azide-alkyne cycloaddition reaction. The well-controlled chemical structures of the grafted copolymers and its precursors are verified by FT-IR spectroscopy, NMR spectroscopy, and GPC characterizations. According to the DSC and XRD results, the polymorphisms of these grafted copolymers are mostly changed from semicrystalline to amorphous depending on the amount of grafted hydantoin. Antibacterial assays are carried out with Bacillus subtilis and two strains of Escherichia coli and show fast antibacterial action.