Ruvanthi N. Kularatne

Recent advances in aliphatic polyesters for drug delivery applications

The use of aliphatic polyesters in drug delivery applications has been a field of significant interest spanning decades. Drug delivery strategies have made abundant use of polyesters in their structures owing to their biocompatibility and biodegradability. The properties afforded from these materials provide many avenues for the tunability of drug delivery systems to suit individual needs of diverse applications. Polyesters can be formed in several different ways, but the most prevalent is the ring-opening polymerization of cyclic esters. When used to form amphiphilic block copolymers, these materials can be utilized to form various drug carriers such as nanoparticles, micelles, and polymersomes. These drug delivery systems can be tailored through the addition of targeting moieties and the addition of stimuli-responsive groups into the polymer chains. There are also different types of polyesters that can be used to modify the degradation rates or mechanical properties. Here, we discuss the reasons that polyesters have become so popular, the current research focuses, and what the future holds for these materials in drug delivery applications. WIREs Nanomed Nanobiotechnol 2017, 9:e1446. doi: 10.1002/wnan.1446 For further resources related to this article, please visit the WIREs website.

Thermoresponsive star-like γ-substituted poly(caprolactone)s for micellar drug delivery

Temperature responsive drug carriers are attractive due to their ability to provide controlled release of the encapsulated cargo based on the use of external stimuli. In this work, 4- and 6-arm thermoresponsive star-like block copolymers were synthesized through the ring-opening polymerization of γ-substituted e-caprolactone monomers γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-e-caprolactone (MEEECL) and γ-ethoxy-e-caprolactone (ECL) using pentaerythritol and myo-inositol as multifunctional initiators. These amphiphilic block copolymers were shown to self-assemble into micelles and were characterized in terms of their feasibility as drug carriers. Both polymers were shown to be thermodynamically stable and demonstrated temperature responsivity in a desirable range for drug delivery, with lower critical solution temperatures of 39.4 °C and 39.8 °C for the 4- and 6-arm polymers, respectively. It was shown that the 6-arm star polymer had a higher drug loading capability and better stability in vitro, allowing it to function as a better vehicle for drug delivery in cytotoxicity experiments. These star polymers show promise as drug carriers due to their biocompatibility, biodegradability, and temperature controlled release of doxorubicin.

Thieno[3,2-b]pyrrole-benzothiadiazole Banana-Shaped Small Molecules for Organic Field-Effect Transistors

We report two banana-shaped organic semiconducting small molecules containing the relatively unexplored thieno[3,2- b]pyrrole with thiophene and furan flanked benzothiadiazole. Theoretical insights gained by DFT calculations, supported by single crystal structures show that furan flanked benzothiadiazole-thieno[3,2- b]pyrrole small molecule has a higher curvature compared to the thiophene flanked small molecule due to the shorter carbon-oxygen bond in furan. Despite similar optical and electrochemical properties, thiophene flanked small molecule shows average hole mobility up to 8 × 10-2 cm2 V-1 s-1, however furan flanked small molecule performs poorly in thin film transistor devices (μh ≈ 5 × 10-6 cm2 V-1 s-1). The drastic difference in hole mobilities was due to the annealing-induced crystallinity which was demonstrated by the out-of-plane grazing incidence X-ray diffraction and surface morphology studies by tapping mode atomic force microscopy analysis.

Influence of functionalized side chains of polythiophene diblock copolymers on the performance of CdSe quantum dot hybrid solar cells

The incorporation of functional groups into the side chains of polythiophenes can improve the phase separation of polymer : nanoparticle hybrid solar cells (HSCs). Our results showed that by introducing 17 mol% thiol functionality in the polymer, the Jsc and Voc can be increased by twofold in polymer : CdSe quantum dot (QD) HSCs.

Histone Deacetylase Inhibitor (HDACi) Conjugated Polycaprolactone for Combination Cancer Therapy

The short chain fatty acid, 4-phenylbutyric acid (PBA), is used for the treatment of urea cycle disorders and sickle cell disease as an endoplasmic reticulum stress inhibitor. PBA is also known as a histone deacetylase inhibitor (HDACi). We report here the effect of combination therapy on HeLa cancer cells using PBA as the HDACi together with the anticancer drug, doxorubicin (DOX). We synthesized γ-4-phenylbutyrate-ε-caprolactone monomer which was polymerized to form poly(γ-4-phenylbutyrate-ε-caprolactone) (PPBCL) homopolymer using NdCl3·3TEP/TIBA (TEP = triethyl phosphate, TIBA = triisobutylaluminum) catalytic system. DOX-loaded nanoparticles were prepared from the PPBCL homopolymer using poly(ethylene glycol) as a surfactant. An encapsulation efficiency as high as 88% was obtained for these nanoparticles. The DOX-loaded nanoparticles showed a cumulative release of >95% of DOX at pH 5 and 37 °C within 12 h, and PBA release was monitored by 1H NMR spectroscopy. The efficiency of the combination therapy can notably be seen in the cytotoxicity study carried out on HeLa cells, where only ∼20% of cell viability was observed after treatment with the DOX-loaded nanoparticles. This drastic cytotoxic effect on HeLa cells is the result of the dual action of DOX and PBA on the DNA strands and the HDAC enzymes, respectively. Overall, this study shows the potential of combination treatment with HDACi and DOX anticancer drug as compared to the treatment with an anticancer drug alone.

Neodymium Catalyst for the Polymerization of Dienes and Polar Vinyl Monomers

Ziegler-Natta catalysts have played a major role in industry for the polymerization of dienes and vinyl monomers. However, due to the deactivation of the catalyst, this system fails to polymerize polar vinyl monomers such as vinyl acetate, methyl methacrylate, and methyl acrylate. Herein, a catalytic system composed of NdCl3 ⋅3TEP/TIBA is reported, which promotes a quasi-living polymerization of dienes and is also active for the homopolymerization of polar vinyl monomers. Additionally, this catalytic system generates polymyrcene-b-polyisoprene and poly(myrcene)-b-poly(methyl methacrylate) diblock copolymers by sequential monomer addition. To encourage the replacement of petroleum-based polymers by environmentally benign biobased polymers, polymerization of β-myrcene is demonstrated with a catalytic activity of ≈106 kg polymer mol Nd-1 h-1 .

Stimuli-responsive poly (ε-caprolactone)s for drug delivery applications

Abstract Poly(caprolactone)s have found extensive use in drug delivery applications due to their attractive properties such as biocompatibility and biodegradability. Significant efforts have been made in recent years to develop stimuli-responsive systems using these polymers. Through the functionalization of e-caprolactone monomers, different stimuli-responsive properties can be instilled to the resulting polymers. Poly(caprolactone)s are usually formed through the ring-opening polymerization of e-caprolactone monomers, which can be accomplished through different mechanisms such as anionic, cationic, or coordination-insertion. The resulting poly(caprolactone)s can be used for various nanocarrier systems including micelles, nanoparticles, dendrimers, or polymersomes. Often, poly(caprolactone)s are used in combination with other polymers to form block copolymers that have hydrophobic and hydrophilic segments which can then form the nanocarriers through self-assembly. Stimuli-responsive nanocarriers created from poly(caprolactone)s can release the drug through either internal or external stimuli. Nanocarriers that are responsive to differences of the internal environment like reduction or pH have attracted a lot of interest in recent years. However, there has also been an interest in nanocarriers that are responsive where the application of an external stimulus, such as temperature or light, triggers the release of the drug. Recently, new effort has been focused to design nanocarriers that are sensitive to multiple stimuli. In this chapter, the extensive use of poly(caprolactone)s in stimuli-responsive nanocarriers will be discussed in detail.

The effect of single atom replacement on organic thin film transistors: case of thieno[3,2-b]pyrrole vs. furo[3,2-b]pyrrole

Despite polypyrrole having higher conductivities compared to polythiophenes, pyrrole based materials have garnered less attention in the organic electronics community due to their instability in air. Construction of stable pyrrolic units could be achieved by fusing relatively unstable pyrrole with stable aromatic rings. In this report, we discuss and compare the organic field-effect transistor performances of the smallest S,N-heteroacene and O,N-heteroacene, thieno[3,2-b]pyrrole and furo[3,2-b]pyrrole, respectively, in donor–acceptor–donor type organic semiconducting small molecules. Since both building blocks are highly electron-rich, thiophene flanked 5,6-difluorobenzo[c][1,2,5]thiadiazole is employed as a central electron-withdrawing unit. The small molecule containing thieno[3,2-b]pyrrole exhibit moderate hole mobilities (10−3 cm2 V−1 s−1) irrespective of the annealing temperature. In contrast, the small molecule bearing furo[3,2-b]pyrrole is completely inactive in field-effect transistors. To the best of our knowledge this is the first report to compare the smallest units of S,N and O,N-heteroacenes for organic field-effect transistors.