Browsing by Author "Rekha, MR"

Now showing 1 - 20 of 24
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    Aggregation of gold nanoparticles followed by methotrexate release enables Raman imaging of drug delivery
    (J Nanoparticle Res., 2012-10) Durgadas, CV; Sharma, CP; Paul, W; Rekha, MR; Sreenivasan, K
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    Aggregation of gold nanoparticles followed by methotrexate release enables Raman imaging of drug delivery into cancer cells
    (JOURNAL OF NANOPARTICLE RESEARCH, 2012) Durgadas, CV; Sharma, CP; Paul, W; Rekha, MR; Sreenivasan, K
    This study refers an aqueous synthesis of methotrexate (MTX)-conjugated gold nanoparticles (GNPs), their interaction with HepG2 cells, and the use of Raman imaging to observe cellular internalization and drug delivery. GNPs of average size 3.5-5 nm were stabilized using the amine terminated bifunctional biocompatible copolymer and amended by conjugating MTX, an anticancer drug. The nanoparticles were released MTX at a faster rate in acidic pH and subsequently found to form aggregates. The Raman signals of cellular components were found to be enhanced by the aggregated particles enabling the mapping to visualize site-specific drug delivery. The methodology seems to have potential in optimizing the characteristics of nanodrug carriers for emptying the cargo precisely at specified sites.
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    Alginate stabilized gold nanoparticle as multidrug carrier: Evaluation of cellular interactions and hemolytic potential
    (CARBOHYDRATE POLYMERS, 2016) Dey, S; Sherly, MCD; Rekha, MR; Sreenivasan, K
    This work delineates the synthesis of curcumin (Ccm) and methotrexate (MTX) conjugated biopolymer stabilized AuNPs (MP@Alg-Ccm AuNPs). The dual drug conjugated nano-vector was characterized by FTIR, 1H NMR and UV-vis spectroscopic techniques. Hydrodynamic diameter and surface charge of the AuNPs were determined by DLS analysis and the spherical particles were visualized by TEM. MP@Alg-Ccm AuNPs exhibited improved cytotoxic potential against C6 glioma and MCF-7 cancer cell lines and was found to be highly hemocompatible. MP@Alg-Ccm AuNPs also exhibited active targeting efficiency against MCF-7 cancer cells due to the presence of "antifolate" drug MTX. Thus MP@Alg-Ccm AuNPs may find potential application in targeted combination chemotherapy for the treatment of cancer. The study is also interesting from the synthetic point of view because, here generation of AuNPs was done using "green chemical" alginate and dual drug conjugated AuNPs were created in two simple reaction steps using "green solvent" water. (C) 2015 Elsevier Ltd. All rights reserved.
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    Alginate stabilized gold nanoparticle as multidrug carrier: Evaluationof cellular interactions and hemolytic potential
    (Carbohydrate Polymers, 2015-09) Dey, S; Sherly, MCD; Rekha, MR; Sreenivasan, K
    This work delineates the synthesis of curcumin (Ccm) and methotrexate (MTX) conjugated biopolymer stabilized AuNPs (MP@Alg–Ccm AuNPs). The dual drug conjugated nano-vector was characterized by FTIR, 1H NMR and UV–vis spectroscopic techniques. Hydrodynamic diameter and surface charge of the AuNPs were determined by DLS analysis and the spherical particles were visualized by TEM. MP@Alg–Ccm AuNPs exhibited improved cytotoxic potential against C6 glioma and MCF-7 cancer cell lines and was found to be highly hemocompatible. MP@Alg–Ccm AuNPs also exhibited active targeting efficiency against MCF-7 cancer cells due to the presence of “antifolate” drug MTX. Thus MP@Alg–Ccm AuNPs may find potential application in targeted combination chemotherapy for the treatment of cancer. The study is also interesting from the synthetic point of view because, here generation of AuNPs was done using “green chemical” alginate and dual drug conjugated AuNPs were created in two simple reaction steps using “green solvent” water
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    Betaine conjugated cationic pullulan as effective gene carrier
    (International Journal of Biological Macromolecules, 2015-02) Lizebona, AA; Rekha, MR
    Polyethyleneimne (PEI) is a very efficient transfecting agent but is toxic due to high charge density. To generate a vector which is efficient and less cytotoxic, PEI was conjugated with pullulan (PPEI). Further conjugation was done on PPEI with zwitter ionic betaine which possess antifouling property. PEI of molecular weight 1.2, 2, and 10 kDa were used in the study. Buffering capacity of pullulan-PEI-betaine (PPB) conjugates was found to be sufficient enough for the polymers to make endosomal escape. The polymers proved to be less cytotoxic and highly hemocompatible than PEI. Nuclear localization of YOYO tagged DNA was observed with the nanoplexes developed using PPEI and PPBs of PEI 10 kDa. Transfection efficiency was evaluated using p53 expressing gene and the live dead assay demonstrated very high transfection efficiency with PPB conjugates of PEI 10 kDa
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    Bioadhesive Hydrophobic Chitosan Microparticles for Oral Delivery of Insulin: In Vitro Characterization and In Vivo Uptake Studies
    (JOURNAL OF APPLIED POLYMER SCIENCE, 2011) Sonia, TA; Rekha, MR; Sharma, CP
    Hydrophobically modified polymeric matrices for drug delivery were developed by N-acylation of chitosan with long(C-18) and medium chain(C-8) fatty acid chlorides like octanoyl and oleoyl chloride. Chemical modifications of chitosan were confirmed by IR spectra and trinitrobenzenesulphonic acid assay. Modified chitosan particles were prepared by ionotropic gelation with sodium tripolyphosphate. Hydrophobic modification was confirmed by contact angle measurements. Scanning electron micrographs showed the presence of compact microparticles. Swelling studies showed that oleoyl chitosan exhibited low swelling profile than octanoyl chitosan at acidic pH. In vitro release profile at pH 7.4 showed that about 90% of insulin was released by 5th hour. ELISA studies proved that the microparticles were capable of maintaining biological activity of insulin. Mucoadhesion studies proved that oleoyl derivative was more mucoadhesive than octanoyl derivative. In vivo uptake studies of fluorescent-labeled microparticles on rat intestinal sections showed that oleoyl chitosan microparticles exhibited significant uptake than octanoyl chitosan. These results suggests that oleoyl moiety would resist degradation by the gastric enzymes and will enhance mucoadhesivity through hydrophobic interactions and also the permeability by loosening the tight junctions, thus making it a useful carrier for oral peptide delivery applications. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 119: 2902-2910, 2011
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    Biomimetic mucin modified PLGA nanoparticles for enhanced blood compatibility
    (JOURNAL OF COLLOID AND INTERFACE SCIENCE, 2013) Thasneem, YM; Rekha, MR; Sajeesh, S; Sharma, CP
    Efforts to develop long circulating polymeric nanoparticles have propelled many strategies in nanoparticle surface modification to bypass immune surveillance and systemic clearance. In this context, our present study reports on the preparation and evaluation of mucin functionalized poly lactic-co-glycolic acid (PLGA) nanoparticles as hemocompatible, cell penetrating nanoparticulate drug delivery system. Amino groups of mucin were conjugated to the terminal carboxylic acid groups on PLGA to be followed by nanoparticle synthesis via standard solvent evaporation technique. Detailed in vitro experiments were performed to illustrate the significance of alternating copolymer structured mucin modified PLGA nanoparticles in terms of enhanced hemocompatibility and cellular uptake. Mucylation proved promising in controlling PLGA nanoparticle- interaction with plasma proteins (opsonins) and blood components via hemolysis, thrombogenecity and complement activation. Besides hemocompatibility, the modified and unmodified nanoparticles were also found to be cytocompatible with L929 and C6 cell lines. The fluorescent and confocal image analysis evaluated the extent of cellular uptake of nanoparticles into C6 cells. Specifically the combination of stealth properties and cellular internalization capacity of mucin modified PLGA nanoparticle (PLGA Mucin) lead us to propose it as a safe, efficient and multifunctional nanoplatform for disease specific intravenous drug delivery applications as far as in vitro experiments are concerned. (C) 2013 Elsevier Inc. All rights reserved.
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    Chitosan/alginate based antioxidant polymeric wound dressings for controlled antibiotic delivery ( Project - 8143 )
    (SCTIMST, 2020-06-20) Rekha, MR; Anilkumar, TV; Maya Nandakumar, A; Harikrishna, VS
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    Collagen synthesis promoting pullulan-PEI-ascorbic acid conjugate as an efficient anti-cancer gene delivery vector
    (CARBOHYDRATE POLYMERS, 2015) Ambattu, LA; Rekha, MR
    Cationized pullulan (pullulan-PEI; PP) was synthesized and further modified with an anti-oxidant molecule, ascorbic acid (PPAA) at various ratios. The nanoplexes formed at an optimum ratio of 4:1 was within a size of 150 nm and had a zeta potential of 9-14 mV. The nanoplexes at this ratio was used for further investigations. The cell internalization and transfection efficiency of these nanoplexes were determined in presence of serum. The internalization and transfection efficiency were found to be unaffected by the presence of fetal bovine serum. Another interesting observation was that this polymer was found to have collagen synthesis promoting property. The collagen synthesis effect of these polymers was quantified and observed that PPAA3 promoted the highest. Transfection efficiency was evaluated by assessing the p53 gene expression in C6 rat glioma cells and cell death was quantified to be 96% by flow cytometry, thus establishing the high efficacy of this polymer. (C) 2015 Elsevier Ltd. All rights reserved.
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    Disulphide cross linked pullulan based cationic polymer for improved gene delivery and efflux pump inhibition
    (COLLOIDS AND SURFACES B-BIOINTERFACES, 2016) Priya, SS; Rekha, MR
    Multidrug resistance is a hurdle to successful cancer chemotherapy. Over expression of P-glycoprotein (P-gp) is a prime contributing factor for drug resistance. In this study, a disulphide cross-linked pullulan-based cationic polymer (PPSS) was synthesized to act simultaneously as gene delivery vehicle and efflux pump inhibitor. The PPSS nanoplexes were of size <200 nm with the zeta potential of +15 to +20 mV. The cytotoxicity studies using C6 and L929 cells showed that PPSS polymers are non-toxic even at high polymer concentrations. The PPSS/pDNA nanoplex showed superior uptake in confocal microscopy with 97% uptake by flow cytometry. The efficacy of efflux pump inhibition by the PPSS nanoplex was established by the enhanced intracellular retention of DOX. The enhanced cell death by p53/PPSS/DOX nanoplexes was attributed to the synergistic effect of P-gp inhibition and p53 transfection efficiency. Therefore, this multifunctional polymeric system may have significant promise for therapeutic application against cancer drug resistance. (C) 2016 Elsevier B.V. All rights reserved.
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    Evaluation of lauryl chitosan graft polyethyleneimine as a potential carrier of genes and anticancer drugs
    (PROCESS BIOCHEMISTRY, 2012) Rajesh, R; Rekha, MR; Sharma, CP
    The conjugation of bioactive molecules to polymeric nanocarriers has the potential to revolutionize current methods of cancer therapy. These nanocarriers can also reduce the undesirable adverse effects of small molecule therapeutic agents. In the present study, the LC-g-PEI (lauryl chitosan graft polyethyleneimine) polymer was synthesized and evaluated as a potential carrier of therapeutic molecules, such as the p53 gene and doxorubicin. The study was designed to investigate the cytotoxicity, drug uptake and transfection efficiency of LC-g-PEI. This polymer had lower interactions with blood components than the unmodified PEI. LC-g-PEI buffered protons, protected DNA from nuclease attack and induced effective gene transfer in the C6 cell line. LC-g-PEI that had incorporated doxorubicin exhibited an enhanced release of this compound at pH 5. LC-g-PEI demonstrated its efficacy in the enhancement of drug uptake and the promotion of gene expression in the C6 cell line. Therefore, LC-g-PEI shows promise as a drug/gene carrier with potential applications in cancer therapy. (c) 2012 Elsevier Ltd. All rights reserved.
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    Falls among Older Adults: A Community-Based Study in Rural Kerala, India
    (Global Journal of Health Science., 2017-11) Rekha, MR; Mini, GK; Kutty, VR
    The study examined the frequency and correlates of falls among community dwelling older adults (≥60 years) in rural Kerala. We did a cross-sectional survey among 202 older adults using a pre-tested structured interview schedule. Falls in the previous year was reported by 27%, among them, 20% fell more than once making a total of 74 falls. Injuries were reported among 58% of the fallers. Slips were the frequent cause of fall (25.6%). Most falls happened outdoors (77%). Age-sex adjusted results of multivariate logistic regression analysis showed that those having any morbidity, those with a history of previous falls and those with no formal education were more likely to fall compared to their counterparts. Awareness programs on the risk of falls for older adults and their close relatives are required in this population. Prevention strategies should focus on those having any morbidity, those with a history of previous falls and those without formal education.
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    Glutamine-Chitosan Microparticles as Oral Insulin Delivery Matrix: In Vitro Characterization
    (JOURNAL OF APPLIED POLYMER SCIENCE, 2011) Rekha, MR; Sharma, CP
    Chitosan at physiological pH lacks positive charge which reduces the mucoadhesivity and permeation enhancing capacity. Therefore glutamine conjugated chitosan (GC) was developed to enhance the protonation of chitosan at intestinal pH. Particles were prepared by sodium tripolyphosphate ionic crosslinking and were evaluated in vitro for its application toward oral insulin delivery. The particles had high positive charge of 35.6 +/- 7.3 mV at physiological pH and a size of 4.434 mu m. The mucoadhesive capacity was established in vitro using rat intestinal tissue. Transepithelial electrical resistance (TEER) and confocal microscopy studies proved the ability of the particles in opening the tight junctions in Caco 2 monolayers. The permeation of fluorescent dextran (M-W 4000; FD4) across intestinal tissue was evaluated using Franz diffusion apparatus. It was observed that the GC particles enhanced the permeation by 1.52 fold in comparison with native chitosan (NC) particles. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 122: 2374-2382, 2011
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    Glutathione-bearing fluorescent polymer-curcumin conjugate enables simultaneous drug delivery and label-free cellular imaging
    (Polymer, 2015-09) Dey, S; Ambattu, LA; Hari, PR; Rekha, MR; Sreenivasan, K
    Curcumin is a natural polyphenol with potential anticancer property. However, the medicinal assets of curcumin cannot be properly utilized due to its low aqueous solubility, instability and subsequent poor bioavailability. Conjugation of curcumin to a suitable hydrophilic polymer is a useful approach for augmenting the aqueous solubility of the drug. In addition, nano-structured materials with intrinsic fluorescence property are of prime importance in the current biomedical domain. In this study, a novel glutathione containing biodegradable, non-toxic and water soluble, fluorescent polymer was developed. Curcumin was covalently conjugated to this polymer to fabricate nano-sized micelle forming fluorescent polymer-curcumin conjugate. The ability of the entity as a safer curcumin delivery vehicle and label-free cellular imaging probe was demonstrated in C6 glioma cells.
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    Intracellular Trafficking Mechanism and Cytosolic Protein Interactions of a Non Viral Gene Delivery Vector: Studies Based on Transferrin Conjugated Pullulan-PEI
    (CURRENT NANOSCIENCE, 2011) Rekha, MR; Sharma, CP
    Compared to viral vectors the intracellular barriers faced by non-viral vectors are high, which lead to lesser transfection efficiency. The various limiting steps include endocytosis, endosomal escape, intracellular stability and mobility, unpacking and nuclear localization. The understanding of these mechanisms for overcoming these barriers is essential for developing gene delivery vectors which can really be used for appropriate clinical/medical applications. Transferrin conjugated pullulan-PEI (PPETf) was developed for neuronal cell targeted gene delivery which was evaluated for its transfection efficiency. The stability of the polymer-DNA nanoplexes in the presence of plasma and cytosolic proteins was evaluated by agarose gel electrophoresis. Time dependent uptake of the nanoplexes by using labeled polymer and YOYO tagged plasmid was employed to understand the uptake mechanism and the sequence of unpacking of DNA from the vector. The uptake pathway, endosomal escape, trafficking etc. are evaluated in the presence of endocytic and microtubilin inhibitors to understand the mechanism of nanoplexes trafficking into and within the cell.
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    Multifunctional polymeric nanoplexes for anticancer co-delivery of p53 and Mitoxantrone
    (Journal of Materials Chemistry B., 2014-09) Mitha, AT; Rekha, MR
    Co-delivery of the anticancer drug, mitoxantrone (MTO) and the gene encoding tumor suppressor protein p53 was evaluated towards anticancer combinatorial therapy. The nanoplatforms developed herein are assembled by coupling b-cyclodextrin and the cationic polymer, polyethyleneimine to a hydrophilic polymer, pullulan (PPEICD). The b-cyclodextrin serves as a nanocontainer for the drug MTO, while the cationic moiety can condense pDNA. Acid base titrations provided insight into the buffering capacity of the PPEICD conjugate. Cytotoxicity studies by MTT assay in HepG2 and C6 cell lines and hemocompatibility studies confirmed the conjugate to be nontoxic and hemocompatible. In vitro release studies of MTO in phosphate buffered saline pH 7.4 showed an initial burst effect followed by a slow drug release. The released data fitted with the Korsmeyer–Peppas model and their diffusional exponents suggest that the drug release from the polymeric system followed diffusion and non-Fickian transport. Combined drug and gene loaded nanoplexes have a more apoptotic effect than either the drug or gene individually as confirmed by MTT assay and live dead assay. This indicated the significance of the combined drug and gene delivery system and the ability of the nanoplatform to overcome the multidrug resistance (MDR) of MTO. Moreover, preference of asialoglycoprotein receptor (ASGPR) mediated internalization for nanoparticle cellular uptake in HepG2 cell lines was identified by treating with the inhibitor asialofetuin. Cell studies in both HepG2 and C6 cell lines demonstrated that the nanoplatform PPEICD can efficiently and selectively deliver both p53 and MTO to cancer cells inducing high cell death.
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    Oral delivery of therapeutic protein/peptide for diabetes - Future perspectives
    (INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2013) Rekha, MR; Sharma, CP
    Diabetes is a metabolic disease and is a major cause of mortality and morbidity in epidemic proportions. A type I diabetic patient is dependent on daily injections of insulin, for survival and also to maintain a normal life, which is uncomfortable, painful and also has deleterious effects. Extensive efforts are being made worldwide for developing noninvasive drug delivery systems, especially via oral route. Oral route is the most widely accepted means of administration. However it is not feasible for direct delivery of peptide and protein drugs. To overcome the gastro-intestinal barriers various types of formulations such as polymeric micro/nanoparticles, liposomes, etc. are investigated. In the recent years lot of advances have taken place in developing and understanding the oral peptide delivery systems. Simultaneously, the development and usage of other peptides having anti-diabetic potentials are also considered for diabetes therapy. In this review we are focusing on the advances reported during the past decade in the field of oral insulin delivery along with the possibility of other peptidic incretin hormones such as GLP-1, exendin-4, for diabetes therapy. (C) 2012 Elsevier B.V. All rights reserved.
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    Oral Insulin Delivery System ( Project 8154 )
    (SCTIMST, 2022-03-31) Rekha, MR
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    Phthalyl Chitosan-Poly(ethylene oxide) Semi-Interpenetrating Polymer Network Microparticles for Oral Protein Delivery: An In Vitro Characterization
    (JOURNAL OF APPLIED POLYMER SCIENCE, 2008) Rekha, MR; Sharma, CP
    Phthalyl chitosan (PC) was synthesized and phthalyl chitosan-poly(ethylene oxide) (PCP) semi-interpenetrating network microparticles were developed by ionic crosslinking with sodium tripolyphosphate. The characterization of PCP particles was done, and these particles were compared with PC and native chitosan (NC) microparticles. The PCP particle size was around 1.3 mu m with a potential of about -28.6 +/- 12.6 mV and an insulin loading efficiency of 89.6%. The release studies were done at pH 1.2 and 7.4, which indicated a minimal release at pH 1.2 compared to that at pH 7.4. The degree of swelling was observed to be higher in PCP than in PC or NC particles. The in vitro mucin-binding capacity and the intestinal mucoadhesiveness of the particles were evaluated. The PCP particles were highly mucoadhesive, and correspondingly, the mucin-binding capacity was lower for these particles; this is necessary for any matrix to be a successful mucoadhesive. These results suggest the usefulness of these particles as a potential candidate for oral insulin-delivery systems. (C) 2008 Wiley Periodicals, Inc. J Appl Polym Sci 110: 2787-2795, 2008