Development of Self-Healing Cement Slurry through the Incorporation of Dual-Encapsulated Polyacrylamide for the Prevention of Water Ingress in Oil Well.

In the present work, a novel cross-linked polymer was synthesized though the anionic polymerization of cyanoacrylate with moisture as an initiator, methylene-bis-acrylamide as a cross-linker, and linseed oil as a spacer. Two layers of the synthesized polymer was coated over polyacrylamide for its homogenous impregnation in Class-G cement slurry for the synthesis of cement core. Fourier Transformation Infrared spectroscopy and X-Ray diffraction spectrum of the synthesized polymer and cement core were obtained to investigate the presence of different functional groups and phases. Moreover, the morphologies of the dual-encapsulated polyacrylamide was observed through scanning electron microscopy. Furthermore, the water-absorption capacity of the synthesized dual-encapsulated polyacrylamide in normal and saline conditions were tested. A cement core impregnated with 16% of dosage of dual-encapsulated polyacrylamide possesses an effective self-healing capability during the water-flow test. Moreover, the maximum linear expansion of the cement core was observed to be 26%. Thus, the impregnation of dual-encapsulated polyacrylamide in cement slurry can exhibit a superior self-healing behavior upon water absorption in an oil well.

Preparation, characterization and in vivo evaluation of pH sensitive, safe quercetin-succinylated chitosan-alginate core-shell-corona nanoparticle for diabetes treatment.

The study aims for development of an efficient polymeric carrier for evaluating pharmaceutical potentialities in modulating the drug profile of quercetin (QUE) in anti-diabetic research. Alginate and succinyl chitosan are focused in this investigation for encapsulating quercetin into core-shell nanoparticles through ionic cross linking. The FT-IR, XRD, NMR, SEM, TEM, drug entrapment and loading efficiency are commenced to examine the efficacy of the prepared nanoparticles in successful quercetin delivery. Obtained results showed the minimum particle size of ∼91.58nm and ∼95% quercetin encapsulation efficiently of the particles with significant pH sensitivity. Kinetics of drug release suggested self-sustained QUE release following the non-fickian trend. A pronounced hypoglycaemic effect and efficient maintenance of glucose homeostasis was evident in diabetic rat after peroral delivery of these quercetin nanoparticles in comparison to free oral quercetin. This suggests the fabrication of an efficient carrier of oral quercetin for diabetes treatment.

Preparation of guar gum scaffold film grafted with ethylenediamine and fish scale collagen, cross-linked with ceftazidime for wound healing application.

Present study describes the synthesis of carboxymethyl guar gum (CMGG) from the native guar gum (GG) and the prepared CMGG is grafted with ethylenediamine (EDA) to form aminated CMGG. Then, fish scale collagen and aminated CMGG are cross-linked by ceftazidime drug through non- covalent ionic interaction. The resultant cross-linked film is subjected to the analysis of (1)HNMR, ATR-FTIR, TGA, SEM and XRD. The TNBS results revealed that 45% of interaction between EDA and CMGG and 90-95% of Ceftazidime is released from aminated CMGG-Ceftazidime-Collagen (ACCC) film after 96h of incubation at physiological pH. In vitro cell line studies reveal the biocompatibility of the cross-linked film and the antimicrobial studies display the growth inhibition against Staphylococcus aureus and Pseudomonas aeruginosa organisms. Overall, the study indicates that the incorporation of Ceftazidime into collagen and aminated CMGG can improve the functional property of aminated CMGG as well as collagen, leading to its biomedical applications.

Modified chitosan encapsulated core-shell Ag Nps for superior antimicrobial and anticancer activity.

This investigation reports a one pot synthesis of silver nanoparticles (Ag Nps) using aqueous solution of chitosan-graft-poly(acrylamide) (Cts-g-PAAm) as a reducing agent and polyethylene glycol (PEG) as a stabilizing agent. The as synthesized Ag Nps was characterized by ultra violet-visible (UV-vis), Fourier transform infrared (FTIR) and X-ray diffraction (XRD) analysis. Field emission scanning electron microscopy (FESEM), dynamic light scattering (DLS) and transmission electron microscopy (TEM) showed that Ag Nps, which were stable upto more than 60 days, were spherical in shape and the particle size was in the range of 5-50 nm. Atomic force microscopy (AFM) image also supported the above obtained result. The prepared Ag Nps exhibited strong antimicrobial activity against different gram positive bacteria (Alkaliphilus, Bascillus substillis, Lysinibascillus) and gram negative bacteria (Enterobacter aerogenus, Vivbrio vulnificus and Escherichia coli) and haemolytic assay revealed its blood compatible nature. The synthesized Ag Nps showed significant cytotoxicity over human cervical HeLa cancer cells and it was found that the inhibitory concentration for 50% cell death (IC50) was 8 µg/ml.

Potential use of curcumin loaded carboxymethylated guar gum grafted gelatin film for biomedical applications.

Present study describes the synthesis of carboxylmethyl guar gum (CMGG) from the native guar gum (GG). Further, the prepared CMGG is grafted with gelatin to form CMGG-g-gelatin and then mixed with curcumin to prepare a biomaterial. The resultant biomaterial is subjected to the analysis of (1)H NMR, ATR-FTIR, TGA, SEM and XRD ensure the carboxymethylation and grafting. The results reveal that 45% of the amine groups of gelatin have been reacted with the--COOH group of CMGG and 90-95% of curcumin is released from CMGG-g-gelatin after 96h of incubation in the phosphate buffer at physiological pH. In vitro cell line studies reveal the biocompatibility of the biomaterial and the antimicrobial studies display the growth inhibition against gram +ve and gram -ve organisms at a considerable level. Overall, the study indicates that the incorporation of curcumin into CMGG-g-gelatin can improve the functional property of guar gum as well as gelatin.

Biofunctionalized surface-modified silver nanoparticles for gene delivery.

Silver nanoparticles (AgNPs) find use in different biomedical applications including wound healing and cancer. We propose that the efficacy of the nanoparticles can be further augmented by using these particles for gene delivery applications. The objective of this work was to engineer biofunctionalized stable AgNPs with good DNA binding ability for efficient transfection and minimal toxicity. Herein, we report on the one-pot facile green synthesis of polyethylene glycol (PEG) stabilized chitosan-g-polyacrylamide modified AgNPs. The size of the PEG stabilized AgNPs was 38 ± 4 nm with a tighter size distribution compared to the unstabilized nanoparticles which showed bimodal distribution of particle sizes of 68 ± 5 nm and 7 ± 4 nm. To enhance the efficiency of gene transfection, the Arg-Gly-Asp-Ser (RGDS) peptide was immobilized on the silver nanoparticles. The transfection efficiency of AgNPs increased significantly after immobilization of the RGDS peptide reaching up to 42 ± 4% and 30 ± 3% in HeLa and A549 cells, respectively, and significantly higher than 34 ± 3% and 23 ± 2%, respectively, with the use of polyethyleneimine (25 kDa). These nanoparticles were found to induce minimal cellular toxicity. Differences in cellular uptake mechanisms with RGDS immobilization resulting in improved efficiency are elucidated. This study presents biofunctionalized AgNPs for potential use as efficient nonviral carriers for gene delivery with minimal cytotoxicity toward augmenting the therapeutic efficacy of AgNPs used in different biomedical products.

pH-sensitive chitosan/alginate core-shell nanoparticles for efficient and safe oral insulin delivery.

Chitosan-alginate (CS/ALG) nanoparticles were prepared by formation of an ionotropic pre-gelation of an alginate (ALG) core entrapping insulin, followed by chitosan (CS) polyelectrolyte complexation, for successful oral insulin administration. Mild preparation process without harsh chemicals is aimed at improving insulin bio-efficiency in in vivo model. The nanoparticles showed an average particle size of 100-200 nm in dynamic light scattering (DLS), with almost spherical or sub-spherical shape and ∼ 85% of insulin encapsulation. Again, retention of almost entire amount of encapsulated insulin in simulated gastric buffer followed by its sustained release in simulated intestinal condition proved its pH sensitivity in in vitro release studies. Significant hypoglycemic effects with improved insulin-relative bioavailability (∼ 8.11%) in in vivo model revealed the efficacy of these core-shell nanoparticles of CS/ALG as an oral insulin carrier. No systemic toxicity was found after its peroral treatment, suggesting these core-shell nanoparticles as a promising device for potential oral insulin delivery.

Viper and cobra venom neutralization by alginate coated multicomponent polyvalent antivenom administered by the oral route.

BACKGROUND: Snake bite causes greater mortality than most of the other neglected tropical diseases. Snake antivenom, although effective in minimizing mortality in developed countries, is not equally so in developing countries due to its poor availability in remote snake infested areas as, and when, required. An alternative approach in this direction could be taken by making orally deliverable polyvalent antivenom formulation, preferably under a globally integrated strategy, for using it as a first aid during transit time from remote trauma sites to hospitals. METHODOLOGY/PRINCIPAL FINDINGS: To address this problem, multiple components of polyvalent antivenom were entrapped in alginate. Structural analysis, scanning electron microscopy, entrapment efficiency, loading capacity, swelling study, in vitro pH sensitive release, acid digestion, mucoadhesive property and venom neutralization were studied in in vitro and in vivo models. Results showed that alginate retained its mucoadhesive, acid protective and pH sensitive swelling property after entrapping antivenom. After pH dependent release from alginate beads, antivenom (ASVS) significantly neutralized phospholipaseA2 activity, hemolysis, lactate dehydrogenase activity and lethality of venom. In ex vivo mice intestinal preparation, ASVS was absorbed significantly through the intestine and it inhibited venom lethality which indicated that all the components of antivenom required for neutralization of venom lethality were retained despite absorption across the intestinal layer. Results from in vivo studies indicated that orally delivered ASVS can significantly neutralize venom effects, depicted by protection against lethality, decreased hemotoxicity and renal toxicity caused by russell viper venom. CONCLUSIONS/SIGNIFICANCE: Alginate was effective in entrapping all the structural components of ASVS, which on release and intestinal absorption effectively reconstituted the function of antivenom in neutralizing viper and cobra venom. Further research in this direction can strategize to counter such dilemma in snake bite management by promoting control release and oral antivenom rendered as a first aid.

Microbial degradation of linseed oil-based elastomer and subsequent accumulation of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer.

The microbial synthesis of environment-friendly poly(3-hydroxybutyrate--co-3-hydroxyvalerate), PHBV, has been performed by using an alkaliphilic microorganism, Alkaliphilus oremlandii OhILAs strain (GenBank Accession number NR_043674.1), at pH 8 and at a temperature of 30-32 °C through the biodegradation of linseed oil-based elastomer. The yield of the copolymer on dry cell weight basis is 90 %. The elastomers used for the biodegradation have been synthesized by cationic polymerization technique. The yield of the PHBV copolymer also varies with the variation of linseed oil content (30-60 %) in the elastomer. Spectroscopic characterization ((1)H NMR and FTIR) of the accumulated product through biodegradation of linseed oil-based elastomers indicates that the accumulated product is a PHBV copolymer consisting of 13.85 mol% of 3-hydroxyvalerate unit. The differential scanning calorimetry (DSC) results indicate a decrease in the melting (T m) and glass transition temperature (T g) of PHBV copolymer with an increase in the content of linseed oil in the elastomer, which is used for the biodegradation. The gel permeation chromatography (GPC) results indicate that the weight average molecular weight (M w) of PHBV copolymer decreases with an increasing concentration of linseed oil in the elastomer. The surface morphology of the elastomer before and after biodegradation is observed under scanning electron microscope (SEM) and atomic force microscope (AFM); these results indicate about porous morphology of the biodegraded elastomer.

pH sensitive N-succinyl chitosan grafted polyacrylamide hydrogel for oral insulin delivery.

pH sensitive PAA/S-chitosan hydrogel was prepared using ammonium persulfate (APS) as an initiator and methylenebisacrylamide (MBA) as a crosslinker for oral insulin delivery. The synthesized copolymer was characterized by Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) study; morphology was observed under scanning electron microscope (SEM). The PAA/S-chitosan with ∼ 38% of insulin loading efficiency (LE) and ∼ 76% of insulin encapsulation efficiency (EE), showed excellent pH sensitivity, retaining ∼ 26% of encapsulated insulin in acidic stomach pH 1.2 and releasing of ∼ 98% of insulin in the intestine (pH 7.4), providing a prolonged attachment with the intestinal tissue. The oral administration of insulin loaded PAA/S-chitosan hydrogel was successful in lowering the blood glucose level of diabetic mice. The bioavailability of insulin was ∼ 4.43%. Furthermore, no lethality or toxicity was documented after its peroral administration. Thus, PAA/S-chitosan hydrogel could serve as a promising oral insulin carrier in future.

PAMAM conjugated chitosan through naphthalimide moiety for enhanced gene transfection efficiency.

Development of efficient and safe gene carrier is the main hurdle for successful gene therapy till date. Poor water solubility and low transfection efficiency of chitosan are the main drawbacks to be efficient gene carrier for successful gene therapy. In this work, PAMAM conjugated chitosan was prepared through naphthalimide moiety by simple substitution reaction. The synthesis of the chitosan conjugates was confirmed by FTIR, (1)H NMR and XRD analyses. The conjugates showed enhanced DNA binding capability compared to that of unmodified chitosan. Moreover, the conjugates showed minimal cytotoxicity compared to that of polyethyleneimine (PEI, 25 kDa) and also showed good blood compatibility with negligible haemolysis. The transfection efficiency of the conjugate was significantly increased compared to that of unmodified chitosan and it also surpassed the transfection efficiency by PEI. Therefore, PAMAM conjugated chitosan can be used safely as alternate efficient gene delivery vector in gene therapy.

Preparation of low toxic fluorescent chitosan-graft-polyethyleneimine copolymer for gene carrier.

Fluorescent chitosan-graft-polyethyleneimine (PEI) copolymer was prepared by incorporating PEI molecule onto chitosan backbone through naphthalimide moiety by simple substitution reaction. 4-Bromo-1,8-naphthalic anhydride was used as fluorescent probe due to its strong fluorescence and good photo-stability property and the presence of a fine tunable bromide functional group in the naphthalimide ring, in this work. The copolymer was characterized by FTIR, elemental analysis and XRD. The fluorescence property of the copolymer was determined by UV-vis spectrometer and spectrofluorometer. The effects of pH and temperature on fluorescence property of the copolymer were also studied. The graft copolymer with degree of substitution 37.6 of PEI onto chitosan showed better complexation ability with DNA at comparatively low N/P (nitrogen to phosphate ratio) ratio 1.0 compared to that of chitosan (N/P ratio 2.0). The cytotoxicity of PEI largely decreased after grafting with chitosan and all the copolymers showed above 50% cell viability even at high polymer concentration (300 µg/mL). Therefore, the prepared fluorescent chitosan-graft-PEI copolymer may be used as a biological marker as well as drug or gene carrier with low toxicity.

Oral insulin delivery by self-assembled chitosan nanoparticles: in vitro and in vivo studies in diabetic animal model.

We have developed self-assembled chitosan/insulin nanoparticles for successful oral insulin delivery. The main purpose of our study is to prepare chitosan/insulin nanoparticles by self-assembly method, to characterize them and to evaluate their efficiency in vivo diabetic model. The size and morphology of the nanoparticles were analyzed by dynamic light scattering (DLS), atomic force microscopy (AFM) and scanning electron microscopy (SEM). The average particle size ranged from 200 to 550 nm, with almost spherical or sub spherical shape. An average insulin encapsulation within the nanoparticles was ~85%. In vitro release study showed that the nanoparticles were also efficient in retaining good amount of insulin in simulated gastric condition, while significant amount of insulin release was noticed in simulated intestinal condition. The oral administrations of chitosan/insulin nanoparticles were effective in lowering the blood glucose level of alloxan-induced diabetic mice. Thus, self-assembled chitosan/insulin nanoparticles show promising effects as potential insulin carrier system in animal models.

Preparation of low molecular weight N-maleated chitosan-graft-PAMAM copolymer for enhanced DNA complexation.

Low molecular weight N-maleated chitosan-graft-PAMAM (polyamidoamine) copolymer was prepared through N-maleated chitosan (NMC) by Michael type addition reaction to enhance its solubility in water as well as its cationic character for enhancement of DNA complexation. FTIR, (1)H NMR, XRD and GPC were used to characterize the graft copolymers. The copolymer showed better DNA complexation ability at low N/P ratio than that of chitosan due to increased surface charge density by the incorporation of PAMAM molecule on to chitosan backbone. The copolymer can effectively protect the DNA toward anionic surfactant. In vitro release study showed efficient DNA release occurred at physiological pH (pH 7.4). In vitro cell cytotoxicity test indicated toward less cytotoxicity of NMC-graft-PAMAM copolymers compared to that of 25 kDa PEI. Thus, the synthesized NMC-graft-PAMAM copolymers have great potential of finding application in drug and gene delivery.

Effect of drying processes and curing time of chitosan-lysine semi-IPN beads on chlorpheniramine maleate delivery.

Beads of semi-interpenetrating polymer network (semi-IPN) have been synthesized from chitosan and lysine with varying amounts of glutaraldehyde solution used as a cross-linker. The cross-linked beads are dried by different drying processes such as air-drying, oven-drying and freeze-drying. These semi-IPNs are characterized under a scanning electron microscope (SEM). Swelling studies of these beads are carried out in different pH (2.0 and 7.4) solutions. The effect of concentration of cross-linking agent and curing period on the swelling as well as on the drug release is analysed. The results indicate that the size of matrix depend on the curing time of beads, concentration of glutaraldehyde and technique of drying. The freeze-dried beads exhibit a relatively higher percentage of swelling in the range of 66-89% as compared to oven-dried beads (53-74%) and air-dried beads (39-61%). The drug loaded beads which are cured for different time intervals followed by drying are tested for in-vitro release of chlorpheniramine maleate (CPM) drug. The rate of drug release from freeze-dried beads is much faster than that from the oven-dried and air-dried beads.