Assessment of PEG on Polymeric Particles Surface, a Key Step in Drug Carrier Translation

Injectable drug nanocarriers have greatly benefited in their clinical development from the addition of a superficial hydrophilic corona to improve their cargo pharmacokinetics. The most studied and used polymer for this purpose is poly(ethylene glycol), PEG. However, in spite of its wide use for over two decades now, there is no general consensus on the optimum PEG chain coverage-density and size required to escape from the mononuclear phagocyte system and to extend the circulation time. Moreover, cellular uptake and active targeting may have conflicting requirements in terms of surface properties of the nanocarriers which complicates even more the optimization process. These persistent issues can be largely attributed to the lack of straightforward characterization techniques to assess the coverage-density, the conformation or the thickness of a PEG layer grafted or adsorbed on a particulate drug carrier and is certainly one of the main reasons why so few clinical applications involving PEG coated particle-based drug delivery systems are under clinical trial so far. The objective of this review is to provide the reader with a brief description of the most relevant techniques used to assess qualitatively or quantitatively PEG chain coverage-density, conformation and layer thickness on polymeric nanoparticles. Emphasis has been made on polymeric particle (solid core) either made of copolymers containing PEG chains or modified after particle formation. Advantages and limitations of each technique are presented as well as methods to calculate PEG coverage-density and to investigate PEG chains conformation on the NP surface.

Effect of Polymer Architecture on the Structural and Biophysical Properties of PEG-PLA Nanoparticles

Polymers made of poly(ethylene glycol) chains grafted to poly(lactic acid) chains (PEG-g-PLA) were used to produce stealth drug nanocarriers. A library of comb-like PEG-g-PLA polymers with different PEG grafting densities was prepared in order to obtain nanocarriers with dense PEG brushes at their surface, stability in suspension, and resistance to protein adsorption. The structural properties of nanoparticles (NPs) produced from these polymers by a surfactant-free method were assessed by DLS, zeta potential, and TEM and were found to be controlled by the amount of PEG present in the polymers. A critical transition from a solid NP structure to a soft particle with either a ���micelle-like��� or ���polymer nano-aggregate��� structure was observed when the PEG content was between 15 to 25% w/w. This structural transition was found to have a profound impact on the size of the NPs, their surface charge, their stability in suspension in presence of salts as well as on the binding of proteins to the surface of the NPs. The arrangement of the PEG-g-PLA chains at the surface of the NPs was investigated by 1H NMR and X-ray photoelectron spectroscopy (XPS). NMR results confirmed that the PEG chains were mostly segregated at the NP surface. Moreover, XPS and quantitative NMR allowed quantifying the PEG chain coverage density at the surface of the solid NPs. Concordance of the results between the two methods was found to be remarkable. Physical-chemical properties of the NPs such as resistance to aggregation in saline environment as well as anti-fouling efficacy were related to the PEG surface density and ultimately to polymer architecture. Resistance to protein adsorption was assessed by isothermal titration calorimetry (ITC) using lysozyme. The results indicate a correlation between PEG surface coverage and level of protein interactions. The results obtained lead us to propose such PEG-g-PLA polymers for nanomedecine development as an alternative to the predominant polyester-PEG diblock polymers.

Effect of polymer architecture on Curcumin 1 encapsulation and release from PEGylated polymer nanoparticles: toward a drug delivery nano-platform to the CNS

We developed a nanoparticles (NPs) library from poly(ethylene glycol)���poly lactic acid comb-like polymers with variable amount of PEG. Curcumin was encapsulated in the NPs with a view to develop a delivery platform to treat diseases involving oxidative stress affecting the CNS. We observed a sharp decrease in size between 15 and 20% w/w of PEG which corresponds to a transition from a large solid particle structure to a ���micelle-like��� or ���polymer nano-aggregate��� structure. Drug loading, loading efficacy and release kinetics were determined. The diffusion coefficients of curcumin in NPs were determined using a mathematical modeling. The higher diffusion was observed for solid particles compared to ���polymer nano-aggregate��� particles. NPs did not present any significant toxicity when tested in vitro on a neuronal cell line. Moreover, the ability of NPs carrying curcumin to prevent oxidative stress was evidenced and linked to polymer architecture and NPs organization. Our study showed the intimate relationship between the polymer architecture and the biophysical properties of the resulting NPs and sheds light on new approaches to design efficient NP-based drug carriers.

Studies on the Synthesis and Transformations of A Few Dibenzoylalkene ��� Type Systems

The aim of the study is to synthesise several dibenzoylakene-type systems such as acenaphthenone-2-ylidene ketones 47 and phenanthrenone-9-ylidene ketones 48 by the condensation reaction of acenaphthenequinone and phenanthrenequinone with methyl ketones. Here studies the thermal and photochemical transformations of acenaphthaenone-2-ylidene ketones 3a-c.These acenaphthenone ���2-ylidene ketones underwent extensive decomposition on heating. The objectives of present study is to synthesise acenaphthenone-2-ylidene ketones by the Claisen-Schmidt condensation of acenaphthenequinone and methyl ketones, it is to synthesise phenanthrenone ���9-ylidene ketones by the Claisen-Schmidt condensation of phenanthrequinone and methyl ketones, thermal studies on acenaphthenone-2-ylidene ketones and phenanthrenone-9-ylidene ketones, photochemical studies on acenaphthenone-2-ylidene ketones and phenanthrenone ���9-ylidene ketones to establish the generality of dibenzoyalkene rearrangement. Cyclic voltammetric studies on these dibezoyalkenes to compare their redox behaviour with that of the cis and trans isomers of dibenzoyl-ethylene, dibenzoylstilbene. These results should provide some information about their reactivity, and to assess and exploit the potential of these systems as quinonemethides. This study conclude that a number of new dibenzolalkene-type systems have been synthesized by the Claisen-Schmidt condensation of 1,2-diketones such as phenanthequinone and acenaphthenequinone with methyl ketones. Some of these compounds have been shown to undergo interesting photochemical transformations. Based on the results it is conclude that phenanthjrenone-9-ylidene ketones are excellent Michael acceptors. Methanol adds to these to yield the corresponding furanols. These furanols are unstable and are slowly converted to phenanthro-2 (3H)-furanones.

Carbon Nanotubes-Reinforced PET Nanocomposite by Melt-Compounding

Poly(ethylene terephthalate) (PET) nanocomposites with single-walled carbon nanotubes (SWNTs) have been prepared by a simple melt compounding method. With increasing concentration (0-3 wt %) of SWNTs, the mechanical and dynamic mechanical properties improved, corresponding to effective reinforcement. Melt rheological characterization indicated the effective entanglements provided by SWNTs in the melt state as well. Thermogravimetric analysis suggested no influence of SWNTs on the thermal stability of PET. Electrical conductivity measurements on the composite films pointed out that the melt compounded SWNTs can result in electrical percolation albeit at concentrations exceeding 2 wt %.

PET-SWNT nanocomposites through ultrasound assisted dissolution-evaporation

Poly(ethylene terephthalate) (PET) based nanocomposites have been prepared with single walled carbon nanotubes (SWNTs) through an ultrasound assisted dissolution-evaporation method. Differential scanning calorimetry studies showed that SWNTs nucleate crystallization in PET at weight fractions as low as 0.3%, as the nanocomposite melt crystallized during cooling at temperature 24 ��C higher than neat PET of identical molecular weight. Isothermal crystallization studies also revealed that SWNTs significantly accelerate the crystallization process. Mechanical properties of the PETSWNT nanocomposites improved as compared to neat PET indicating the effective reinforcement provided by nanotubes in the polymer matrix. Electrical conductivity measurements on the nanocomposite films showed that SWNTs at concentrations exceeding 1 wt% in the PET matrix result in electrical percolation. Comparison of crystallization, conductivity and transmission electron microscopy studies revealed that ultrasound assisted dissolution-evaporation method enables more effective dispersion of SWNTs in the PET matrix as compared to the melt compounding method

Studies on the Synthesis and Transformations of a Few Dibenzoylalkene-type Systems

The aim of the study is to synthesise several dibenzoylakene-type systems such as acenaphthenone-2-ylidene ketones 47 and phenanthrenone-9-ylidene ketones 48 by the condensation reaction of acenaphthenequinone and phenanthrenequinone with methyl ketones. Here studies the thermal and photochemical transformations of acenaphthaenone-2-ylidene ketones 3a-c.These acenaphthenone ���2-ylidene ketones underwent extensive decomposition on heating. The objectives of present study is to synthesise acenaphthenone-2-ylidene ketones by the Claisen-Schmidt condensation of acenaphthenequinone and methyl ketones, it is to synthesise phenanthrenone ���9-ylidene ketones by the Claisen-Schmidt condensation of phenanthrequinone and methyl ketones, thermal studies on acenaphthenone-2-ylidene ketones and phenanthrenone-9-ylidene ketones, photochemical studies on acenaphthenone-2-ylidene ketones and phenanthrenone ���9-ylidene ketones to establish the generality of dibenzoyalkene rearrangement. Cyclic voltammetric studies on these dibezoyalkenes to compare their redox behaviour with that of the cis and trans isomers of dibenzoyl-ethylene, dibenzoylstilbene. These results should provide some information about their reactivity, and to assess and exploit the potential of these systems as quinonemethides. This study conclude that a number of new dibenzolalkene-type systems have been synthesized by the Claisen-Schmidt condensation of 1,2-diketones such as phenanthequinone and acenaphthenequinone with methyl ketones. Some of these compounds have been shown to undergo interesting photochemical transformations. Based on the results it is conclude that phenanthjrenone-9-ylidene ketones are excellent Michael acceptors. Methanol adds to these to yield the corresponding furanols. These furanols are unstable and are slowly converted to phenanthro-2 (3H)-furanones

Modification of Polypropylene/Glass Fiber Composites with Nanosilica

Poly(propylene) (PP) reinforced with short glass fiber was modified with precipitated nanosilica (pnS) by melt mixing. The weight of the glass fiber was varied by keeping the pnS at optimum level. The properties of the composites were studied using universal testing machine, dynamic mechanic analyser (DMA), differential Scanning calorimetry (DSC) and thermo gravimetric analyser (TGA). The amount of the glass fiber required for a particular modulus could be reduced by the addition of nanosilica.

Polymer Nanocomposites: Crystallization, Reinforcement and Conductivity through SWNTs

The current research investigates the possibility of using single walled carbon nanotubes (SWNTs) as filler in polymers to impart several properties to the matrix polymer. SWNTs in a polymer matrix like poly(ethylene terephthalate) induce nucleation in its melt crystallization, provide effective reinforcement and impart electrical conductivity. We adopt a simple melt compounding technique for incorporating the nanotubes into the polymer matrix. For attaining a better dispersion of the filler, an ultrasound assisted dissolution-evaporation method has also been tried. The resulting enhancement in the materials properties indicates an improved disentanglement of the nanotube ropes, which in turn provides effective matrix-filler interaction. PET-SWNT nanocomposite fibers prepared through melt spinning followed by subsequent drawing are also found to have significantly higher mechanical propertiesas compared to pristine PET fiber.SWNTs also find applications in composites based on elastomers such as natural rubber as they can impart electrical conductivity with simultaneous improvement in the mechanical properties.

Modification of Short Fibre Reinforced pp and HDPE Using Nanosilica

The present study was undertaken to prepare nanosilica by a simple cost effective means and to use it as a potential nanomodifier in thermoplastic matrices and to develop useful composites. Nanosilica was prepared from sodium silicate and dilute hydrochloric acid by polymer induced crystallization technique under controlled conditions. The silica surface was modified by silane coupling agent to decrease the agglomeration and thus to increase the reinforcement with polymer. The pristine nanosilica and modified nanosilica were used to make nano-micro hybrid composites. Short glass fibres and nylon fibres were used as microfillers. The hybrid nanocomposites based on Polypropylene (PP) and High density poly ethylene (HOPE) are prepared. The mechanical, thermal, crystallization and dynamic mechanical properties of the composites are evaluated.

Solvent Effect on Absolute Fluorescence Quantum Yield of Rhodamine 6G Determined Using Transient Thermal Lens Technique

Dual beam thermal lens tecbnique is successfully employed for the determination of absolute Fluorescence quantum yield of rhodamine 6G lnser dye in different solvents. A 532 nm radiation from a Q-switched Nd:YAG laser was used for the excitation purpose. The fluorescence quantum yield values are found to be strongly influenced by environmental effects. It has been observed that fluorescence yield is greater for rhodamine 6G in ethylene glycol system than in water or in methanol. Our results also indicate that parameters like concentration of the dye solution, aggregate formation and excited state absorption affect the absolute values of fluorescence yield significantly.

NANO - ZINC OXIDE: A Novel Modifier for Thermoplastics

Various synthesis routes have been developed in recent years for the preparation of nanoparticles. One of those methods is polymer induced crystallization. The first objective of the present work was to prepare nano ZnO powder by polymer induced crystallization in chitosan solution and to characterize the material using different techniques like TEM, SEM, XRD, FTLR, UV spectroscopy, TGA, DSC etc.The second object of the study is to prepare composites using nano ZnO. It has been undertaken to explore the potential of nano ZnO as reinforcement in engineering as well as commodity thermoplastics to widen their application spectra. We selected three engineering thermoplastics like [poly ethylene terephthalate, polyamide 6, and polycarbonate] and three commodity plastics like [polypropylene, high density polyethylene, and polystyrene] for the study. To date one of the few disadvantages associated with nanoparticle incorporation has concerned toughness and impact performance. Modification of polymers could reduce impact performance. The present study also focused on whether nano ZnO can act as a modifier for thennoplastics, without sacrificing their impact strength.

Studies on the Production, Properties and Processability of Low Protein Latex

Latex protein allergy is a serious problem faced by users of natural rubber latex products. This is severe in health care workers, who are constantly using latex products like examination gloves, surgical gloves etc. Out of the total proteins only a small fraction is extractable and only these proteins cause allergic reactions in sensitized people. Enzymic deproteinisation of latex and leaching and chlorination of latex products are the common methods used to reduce the severity of the problem.Enzyme deproteinisation is a cubersome process involving high cost and process loss.Physical properties of such films are poor. Leaching is a lengthy process and in leached latex products presence of extractable proteins is observed on further storing. Chlorination causes yellowing of latex products and reduction in tensile properties.In this context a more simple process of removal of extractable proteins from latex itself was investigated. This thesis reports the application of poly propylene glycol (PPG) to displace extractable proteins from natural latex. PPG is added to 60 % centrifuged natural latex to the extent of 0.2 % m/rn, subssequently diluted to 30 % dry rubber content and again concentrated to obtain a low protein latex.Dilution of concentrated latex and subsequent concentration lead to a total reduction in non - rubber solids in the concentrate, especially proteins and reduction in the ionic concentration in the aqueous phase of the latex. It has been reported that proteins in natural rubber / latex affect its behaviour in the vulcanisation process. Ionic concentration in the aqueous phase of latex influence the stability, viscosity and flow behaviour of natural latex. Hence, a detailed technological evaluation was carried out on this low protein latex. In this study, low protein latex was compared with single centrifuged latex ( the raw material to almost every latex product), double centrifuged latex ( because dilution and second concentration of latex is accompanied by protein removal to some extent and reduction in the ionic concentration of the aqueous phase of latex.). Studies were conducted on Sulphur cure in conventional and EV systems under conditions of post ~ cure and prevulcanisation of latex. Studies were conducted on radiation cure in latex stage. Extractable protein content in vulcanised low protein latex films are observed to be very low. lt is observed that this low protein latex is some what slower curing than single centrifuged latex, but faster than double centrifuged latex. Modulus of low protein latex films were slightly low. In general physical properties of vulcanised low protein latex films are only siightly lower than single centrifuged latex. Ageing properties of the low protein latex films were satisfactory. Viscosity and flow behaviour of low protein latex is much better than double centrifuged latex and almost comparable to single centrifuged latex. On observing that the physical properties and flow behaviour of low protein latex was satisfactory, it was used for the preparation of examination gloves and the gloves were evaluated. It is observed that the properties are conforming to the Indian Standard Specifications. It is thus observed that PPG treatment of natural latex is a simple process of preparing low protein latex. Extractable protein content in these films are very low.The physical properties of the films are comparable to ordinary centrifuged latex and better than conventionally deprotenized latex films. This latex can be used for the production of examination gloves.

Studies on meroplankton

Plankton community, drawn from a vary wide variety of animal phyla, formed the basic food supply of marine life and indicators of water mass. The term meroplankton generally referred to that portion of the zooplankton which is transient in nature, remaining rest of their lives in the nektonic or benthic environment. This group was selected for intensive studies, considering the role of meroplankton in the economy of the sea and the scarcity of literature on them from the Indian Ocean. The preser .udy besides providing information regarding the fixation and preservation !e _ iniques and biochemical aspects of tropical meroplankton, also consolidates information regarding their zoogeography in the Indian Ocean region, with a view to amplifying the limited information available from this area. The distribution studies are based on the collections made during the International Indian Ocean Expedition (1960-65), whereas the material for preservation and biochemical studies was collected from the coastal waters during 1968-1978. Salient features:- 2% of formaldehyde buffered with 2% borax, added to the plankton in the ratio of 9:1 was found the best fixative. On fixation the plankton underwent shrinkage due to loss of 15 to 87% water. Addition of antioxidants prevented colour fading. Narcotization by different specific reagents prior to fixation reduced distortions due to violent reaction and improved morphological conditions. One percent formaldehyde solution in sea water buffered with borax or neutralised with calcium carbonate perfectly preserved majority of meroplankton. Equally good was one percent propylene phenoxetol buffered with borax. Biochemical compostion of vaioous taxa showed variations according to their age class, size groups metamorphosing stage, feeding mechanism, type of organism fed and time of collection. General distribution studies of 4 meroplankton taxa - Anthozoan larvae, cirripedia larvae, sipunculoid larvae and gastropod larvae stowed abundance in the coastal areas especially during the SW monsoon period. Based on the larval distribution different zoo-geographical areas in the Indian Ocean are differentiated.

Studies on polyurethane elastomers based on liquid natural rubber

In the present study, the photochemical depolymerisation of NR in toluene, in presence of H202 and a homogenizing solvent (Methanol/Tetrahydro��� furan) so as to get hydroxyl terminated liquid natural rubber (HTNR) has been carried out. The copolymeri��� sation of this product with butane 1,4 diol and toluene 2,4 diisocyanate in presence of a catalyst, dibutyl tin dilaurate, to produce polyurethanes with HTNR soft segments is also reported. The preparation of block copolymers based on poly(ethylene oxide) with varying molecular weights and HTNR are also discussed along with a detailed study on their thermal and mechanical properties