Dhanjay Jhurry

Controlled polymerization of lactides at ambient temperature using [5‐Cl‐salen]AlOMe

The Schiff-base aluminium complex [5-Cl-salen]AlOMe (2) is shown to be a room temperature initiator for controlled ring-opening polymerization of D,L- and L-lactides; the molecular structure of the precursor [5-Cl-salen]AlMe (1) reveals a distorted trigonal bipyramidal geometry.

Synthesis of polylactides by new aluminium Schoff's base complexes

The kinetics of DL-lactide polymerization was studied in CH2Cl2 and dioxane at 25°C and in toluene at 70°C with different aluminium Schiffs base initiators namely HAPENAlOMe, HAPENAlOiPr, 5-ClSALENAlOiPr and 5-ClSALOPHENAlOiPr. It was observed that HAPEN-type complexes derived from 2-hydroxyacetophenone lead to much faster polymerization as compared to SALEN- or 5-ClSALEN-type initiators derived from salicylaldehyde. Moreover, substitution of the methoxide group coordinated to the central aluminium by an isopropoxide group brings about an increase in the polymerization rate but leads to transesterification reactions at much lower percentage conversion. On the other hand, replacement of the flexible ethylene diamino group by the more rigid phenylenediamino substituent slows down considerably the polymerization reaction. Analysis of the microstructure of all poly(DL-lactides) obtained revealed the presence of isotactic sequences in agreement with a first order Markovian statistics.

Anionic polymerization of d,l-lactide initiated by lithium diisopropylamide

The anionic polymerization of d,l-lactide initiated by lithium diisopropylamide.monoTHF complex was performed in different solvents and at various temperatures. No polymerization took place in THF solution. In dioxane at 25°C the polymerization is fast and goes up to completion in few minutes. In toluene, due to solubility requirements, polymerizations were run at 70°C. At initial stage of polymerization Mw/Mns were quite narrow, but at higher conversion a significant broadening occurred due to transesterification reactions. The latter were identified by 13C NMR analysis, while MALDI-TOF spectra revealed the simultaneous presence of cyclic and linear oligomers substantiating the occurrence of both intra and inter ester exchange processes. At low conversion, polymers exhibited a highly syndiotactic microstructure.

Synthesis and characterization of polymers containing linear sugar moieties as side groups

Abstract The synthesis of a water-soluble monomer, namely 4-vinylphenyl- d -gluco( d -manno)hexitol (4) derived from d -gluconolactone, is here presented. The homopolymerization of the vinylsugar has been conducted in both aqueous and organic media using free-radical initiators. High-molar-mass water-soluble polymers are obtained. The copolymerization behavior of the vinylphenyl sugar monomer with a hydrophilic monomer such as acrylamide, as well as with a hydrophobic monomer such as styrene, has been investigated. Statistical- and block-type copolymers have thus been prepared. The structures of the polymers were confirmed by NMR and their thermal properties examined by DSC.

Polydioxanone-based bio-materials for tissue engineering and drug/gene delivery applications

Since the commercialization of polydioxanone (PDX) as a biodegradable monofilament suture by Ethicon in 1981, the polymer has received only limited interest until recently. The limitations of polylactide-co-glycolide (PLGA) coupled with the growing need for materials with enhanced features and the advent of new fabrication techniques such as electrospinning have revived interest for PDX in medical devices, tissue engineering and drug delivery applications. Electrospun PDX mats show comparable mechanical properties as the major structural components of native vascular extracellular matrix (ECM) i.e. collagen and elastin. In addition, PDXs unique shape memory property provides rebound and kink resistance when fabricated into vascular conduits. The synthesis of methyl dioxanone (MeDX) monomer and copolymers of dioxanone (DX) and MeDX have opened up new perspectives for poly(ester-ether)s, enabling the design of the next generation of tissue engineering scaffolds for application in regenerating such tissues as arteries, peripheral nerve and bone. Tailoring of polymer properties and their formulation as nanoparticles, nanomicelles or nanofibers have brought along important developments in the area of controlled drug or gene delivery. This paper reviews the synthesis of PDX and its copolymers and provides for the first time an exhaustive account of its applications in the (bio)medical field with focus on tissue engineering and drug/gene delivery.

New avenues for improving pancreatic ductal adenocarcinoma (PDAC) treatment: Selective stroma depletion combined with nano drug delivery.

The effectiveness of chemotherapy in PDAC is hampered by the dynamic interaction between stroma and cancer cell. The two opposing schools of thought - non-depletion of the stroma vs its depletion - to better drug efficacy are here discussed. Disrupting stroma-cancer cell interaction to reduce tumor progression and promote apoptosis is identified as the new direction of treatment for PDAC. Clinical data have shown that elimination of fibrosis and blockade of the Hedgehog pathway in stroma effectively promote drug delivery to tumor site and apoptosis. Reduced stiffness of ECM, lower fibrosis, higher permeability and higher blood flow after stroma depletion increase drug delivery. Combination strategies involving selective stroma depletion coupled with chemotherapy is currently proving to be the most efficient at clinical level. Striking the right balance between fibrosis depletion and angiogenesis promotion resulting in enhanced drug delivery and apoptosis is a major challenge. The use of nano drug delivery devices coupled with stroma depletion is emerging as the next phase treatment for PDAC. The breakthrough to combat PDAC will likely be a combination of early diagnosis and the emerging chemotherapy strategies.

Cell-matrix mechanical interaction in electrospun polymeric scaffolds for tissue engineering: Implications for scaffold design and performance

Engineered scaffolds produced by electrospinning of biodegradable polymers offer a 3D, nanofibrous environment with controllable structural, chemical, and mechanical properties that mimic the extracellular matrix of native tissues and have shown promise for a number of tissue engineering applications. The microscale mechanical interactions between cells and electrospun matrices drive cell behaviors including migration and differentiation that are critical to promote tissue regeneration. Recent developments in understanding these mechanical interactions in electrospun environments are reviewed, with emphasis on how fiber geometry and polymer structure impact on the local mechanical properties of scaffolds, how altering the micromechanics cues cell behaviors, and how, in turn, cellular and extrinsic forces exerted on the matrix mechanically remodel an electrospun scaffold throughout tissue development. Techniques used to measure and visualize these mechanical interactions are described. We provide a critical outlook on technological gaps that must be overcome to advance the ability to design, assess, and manipulate the mechanical environment in electrospun scaffolds toward constructs that may be successfully applied in tissue engineering and regenerative medicine. STATEMENT OF SIGNIFICANCE Tissue engineering requires design of scaffolds that interact with cells to promote tissue development. Electrospinning is a promising technique for fabricating fibrous, biomimetic scaffolds. Effects of electrospun matrix microstructure and biochemical properties on cell behavior have been extensively reviewed previously; here, we consider cell-matrix interaction from a mechanical perspective. Micromechanical properties as a driver of cell behavior has been well established in planar substrates, but more recently, many studies have provided new insights into mechanical interaction in fibrillar, electrospun environments. This review provides readers with an overview of how electrospun scaffold mechanics and cell behavior work in a dynamic feedback loop to drive tissue development, and discusses opportunities for improved design of mechanical environments that are conducive to tissue development.

Sucrose-based polymers: Polyurethanes with sucrose in the main chain

Abstract Polyurethanes derived from diisocyanates and sucrose containing either blocked or free hydroxyl groups were synthesized by polycondensation and their dimensions and structures characterized. It was shown that under certain conditions, crosslinking can be avoided and polycondensates based on sucrose-free hydroxyl groups that are soluble both in polar organic solvents and in water can be obtained. However, analysis of their 13C NMR spectra shows that addition does not proceed selectively at hydroxyls 6 and 6′ as we might expect, thus suggesting that the polyurethanes do not possess linear structures. This was confirmed by carrying out the step-growth addition of 6,6′-dichlorosucrose on 1,4-phenylene diisocyanate.

Third generation poly(hydroxyacid) composite scaffolds for tissue engineering

Bone tissue engineering based on scaffolds is quite a complex process as a whole gamut of criteria needs to be satisfied to promote cellular attachment, proliferation and differentiation: biocompatibility, right surface properties, adequate mechanical performance, controlled bioresorbability, osteoconductivity, angiogenic cues, and vascularization. Third generation scaffolds are more of composite types to maximize biological-mechanical-chemical properties. In the present review, our focus is on the performance of micro-organism-derived polyhydroxyalkanoates (PHAs)-polyhydroxybutyrate (PHB) and polyhydroxybutyrate-co-valerate (PHBV)-composite scaffolds with ceramics and natural polymers for tissue engineering applications with emphasis on bone tissue. We particularly emphasize on how material properties of the composites affect scaffold performance. PHA-based composites have demonstrated their biocompatibility with a range of tissues and their capacity to induce osteogenesis due to their piezoelectric properties. Electrospun PHB/PHBV fiber mesh in combination with human adipose tissue-derived stem cells (hASCs) were shown to improve vascularization in engineered bone tissues. For nerve and skin tissue engineering applications, natural polymers such as collagen and chitosan remain the gold standard but there is scope for development of scaffolds combining PHAs with other natural polymers which can address some of the limitations such as brittleness, lack of bioactivity and slow degradation rate presented by the latter.

Naltrexone: a review of existing sustained drug delivery systems and emerging nano-based systems.

Narcotic antagonists such as naltrexone (NTX) have shown some efficiency in the treatment of both opiate addiction and alcohol dependence. A few review articles have focused on clinical findings and pharmacogenetics of NTX, advantages and limitations of sustained release systems as well as pharmacological studies of NTX depot formulations for the treatment of alcohol and opioid dependency. To date, three NTX implant systems have been developed and tested in humans. In this review, we summarize the latest clinical data on commercially available injectable and implantable NTX-sustained release systems and discuss their safety and tolerability aspects. Emphasis is also laid on recent developments in the area of nanodrug delivery such as NTX-loaded micelles and nanogels as well as related research avenues. Due to their ability to increase the therapeutic index and to improve the selectivity of drugs (targeted delivery), nanodrug delivery systems are considered as promising sustainable drug carriers for NTX in addressing opiate and alcohol dependence.