Montmorillonite-Chitosan based Nano-Composites and Applications

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Chitosan is a biopolymer gaining widespread attention due to its astounding physicochemical characteristics and properties, including biocompatibility, mucoadhesive, biodegradability, low toxicity, and polycationic nature. Furthermore, chitosan can be processed to obtain different nanostructures such as nanoparticles, nano-vehicles, nanocapsules, scaffolds, etc. Montmorillonite (MMT) is a major constituent of bentonite clay, which has the ability to ameliorate the mechanical strength of polymers including chitosan when combined with it due to its layered structure. Bionanocomposite is a term used to describe composite materials which encompass component(s) with natural inception and the obtained particles with at the minimum one size ranging from 1 nm to 100 nm. Chitosan-based nanocomposite with MMT showed a proven record of wide applications in drug delivery, medical, biomedical, and pharmaceutical fields. This chapter provides an insight into the various characteristics and properties of chitosan and MMT, different methods to develop their composite, and various forms of the resulted composite along a thorough description of applications.

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  • 10.2174/0929867326666190222193357
Nanostructured Calcium-based Biomaterials and their Application in Drug Delivery.
  • Sep 11, 2020
  • Current Medicinal Chemistry
  • Li-Juan Yi + 3 more

In the past several decades, various types of nanostructured biomaterials have been developed. These nanostructured biomaterials have promising applications in biomedical fields such as bone repair, tissue engineering, drug delivery, gene delivery, antibacterial agents, and bioimaging. Nanostructured biomaterials with high biocompatibility, including calcium phosphate, hydroxyapatite, and calcium silicate, are ideal candidates for drug delivery. This review article is not intended to offer a comprehensive review of the nanostructured biomaterials and their application in drug delivery but rather presents a brief summary of the recent progress in this field. Our recent endeavors in the research of nanostructured biomaterials for drug delivery are also summarized. Special attention is paid to the synthesis and properties of nanostructured biomaterials and their application in drug delivery with the use of typical examples. Finally, we discuss the problems and future perspectives of nanostructured biomaterials in the drug delivery field.

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  • Cite Count Icon 25
  • 10.1016/j.ijbiomac.2024.131122
Research progresses on carboxymethyl xanthan gum: Review of synthesis, physicochemical properties, rheological characterization and applications in drug delivery
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  • International Journal of Biological Macromolecules
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Research progresses on carboxymethyl xanthan gum: Review of synthesis, physicochemical properties, rheological characterization and applications in drug delivery

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Natural Polysaccharides in Drug Delivery and Biomedical Applications
  • Jan 1, 2019
  • Saquib Hasnain + 1 more

Natural Polysaccharides in Drug Delivery and Biomedical Applications

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  • Cite Count Icon 2
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Graphene and Graphene-Based Nanomaterials
  • Nov 17, 2021
  • Abid Hussain + 2 more

Soon after the discovery in 2004, graphene gained a lot of attention in the scientific community and, thus, has been broadly investigated due to its unique features and immense applications in the field of nanomedicine, bioimaging, biosensors, drug delivery, biomedical application, and pharmaceuticals. Graphene is a single-layered, two-dimensional carbon molecule having hexagonal packed structure arranged in a honeycomb cross-section manner. Graphene and its derivatives such as graphene oxide (GO), graphene quantum dots (GQDs), and monolayer and bilayer graphene are vastly investigated for their scientific applications. Among different applications to date, graphene was successfully used for the first time as a drug delivery vehicle for cancer chemotherapy in 2008. Since then, graphene and graphene-based nanomaterials were massively studied for their applications in drug and gene delivery, cancer treatment, and its diagnosis owing to their unique physicochemical properties. This chapter explores the basic knowledge about the history, chemistry, and types of graphene with a spotlight on the preparation, characterization, and functionalization of graphene oxide nanoparticles. Moreover, due to the ample use of graphene oxide nanomaterials in the biomedical field, we also discuss its applications in cancer therapy and cancer diagnosis. Furthermore, this chapter also highlights the future perspectives of graphene and graphene-based materials.

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Advanced Nanosystems for Clinical Translation
  • Jan 1, 2021
  • Advanced Therapeutics
  • Christian Celia + 2 more

This special issue is dedicated, but not limited to, the “1st International Northern-Southern Europe Workshop in Nanomedicine” held in the city of Chieti (Abruzzi, Italy) between January 15–17, 2020, before the COVID-19 pandemic lockdown. The workshop aimed to bring together a vast number of experts with extensive experience in the field of nanomedicine from the northern and southern parts of Europe, but also worldwide to discuss and network on how to foster basic science in translational and personalized nanomedicine for drug delivery applications, including anti-cancer research, regenerative medicine, cardiovascular diseases, polymer and supramolecular chemistry towards reliable pre-clinical and clinical assessment. The final goal of the workshop was to highlight the impact of nanomedicine in pharmaceutical companies and how to create bridges and connections between companies, academia, young and senior scientists. Nanomedicine is the medical application of nanotechnology in different fields of bio- and nano-technology, as well as drug delivery and involves areas related to applications, toxicity and environmental impact of nanoscale materials.[1, 2] Nanomaterials have sizes and structure similar to that of bio- and macro-molecules and their functionalization provides specific properties for tailoring precision medicine and application for many diseases, thus providing different therapeutic options for patients.[3] In particular, nanomedicine integrates different research areas, such as biology, physics, chemistry, materials sciences, nanotechnology and drug delivery in order to develop clinical tools and devices for advanced therapies to patients.[4, 5] In this scenario, nanosystems, having different compositions, combined with nanomaterial properties may foster the translation of basic science in personalized nanomedicines for anti-cancer research, regenerative medicine, cardiovascular diseases, polymer and supramolecular chemistry towards a reliable pre-clinical and clinical assessment.[6-9] Although transparency and reproducibility in nanomedicines is still under discussion,[10] there has been an extensive increase in the benefits of nanomedicine available to patients.[11] This special issue on “Advanced Nanosystems for Clinical Translation” addresses a cutting-edge and multidisciplinary field and emphasises the clinical translation of recently developed advanced nanosystems for a range of readers working both in the academic and industry worlds. Researchers, clinical doctors, related scientific and technical specialists working in chemistry, biomedical sciences, materials science, biology and medicine provide suitable scientific contribution in these fields. There is no doubt that nanomedicine is a cross-, multi-, inter- and trans-disciplinary field of research and the examples below, demonstrate exactly how nanoparticles and nanomedicines are revolutionizing and reshaping the pharmaceutical and biomedical fields. This special issue collects 19 amazing contributions, including eight review papers, nine full papers and two progress reports, which broadly cover the various important topics within the field of nanomedicine. Worldwide contributions are part of this special issue and address the impact of nanosystems in basic science, translational and personalized medicine for the treatment of various diseases. In the field of ultrathin fibers, Prof. Cui and co-workers. from Shanghai Jiao Tong University School of Medicine (article number 2000096) provided a novel analysis of the diverse roles of electrospun nanofibrous scaffolds and summarized recent advances in exploiting their binary attributes for applications in biomedicine. The authors firstly introduced the development of techniques for electrospinning, specifically the engineering of electrospun nanofibers, and then discussed the scaffold applications for cell migration, adhesion, proliferation, and accelerating regeneration in cardiac, nerve, skeletal muscle, bone tissue, and wound healing, as well as the scaffold inhibitory properties in cancer treatments, antibacterial applications, anti-adhesion, anti-scarring, and inhibition of thrombus formation. In the field of brain drug delivery, Prof. Merkel and co-workers from Ludwig-Maximilians-University of Munich (article number 2000092) discussed the impact and properties of apolipoprotein E (ApoE)-functionalized polymeric nanoparticles (NPs) for the transport of drugs, such as dalargin, loperamide, doxorubicin, and nerve growth factor across the brain-blood-barrier (BBB) via low density lipoprotein receptor. The authors also described the direct and indirect coating processes of Apo-E to NPs, their impact in transcytosis mediated transport across the BBB and in vivo models simulating the central nervous system-relevant diseases, such as Alzheimer's or Parkinson's diseases and cerebral cancer. In the field of anticancer therapy, Prof. Teesalu and co-workers from University of Tartu (article number 2000097) discussed the synthesis of silver nanoparticles (AgNP) coated with monomethyl auristatin E (MMAE), a lysosomal protease cathepsin B sensitive linker, and functionalized with a prototypic CendR peptide (RPARPAR), that targets neuropilin-1 (NRP-1), for the treatment of pancreatic and melanoma cells. The authors demonstrated, for example, that RPARPAR-MMAE-AgNPs are internalized and induced apoptotic cell death in NRP-1-positive PPC-1 prostate cancer cells, while sparing NRP-1-negative M21 melanoma cells. In the same field, Prof. Cameron and co-workers from University of Nottingham (article number 2000103) investigated the synthesis of amphiphilic block co-polymers composed of doxorubicin-loaded poly(ethylene glycol)-copoly(lactide)-copoly(2-((tert-butoxycarbonyl)amino)-3-propyl carbonate) and studied its anticancer property in 2D cell models and in 3D spheroids of triple negative breast cancer cells, as well as in an aggressive orthotopic triple negative breast cancer mouse model. In another study, Prof. Kostarelos and co-workers from University of Manchester (article number 2000109) investigated the interaction of graphene oxide (GO) sheets with in vitro (three-dimensional spheroids) and in vivo (orthotopic xenograft) models of glioblastoma (GB). In vitro experiments with spheroids, showed that GO flakes are passively translocated into the spheroids with little internalization in tumor cells, and did not cause cytotoxicity and only induced small changes in gene and protein expression. In vivo, the intracranially administered GO also showed extensive distribution throughout the tumor mass and had no impact on tumor growth and progression for the duration of the study. Furthermore, Prof. Fresta and co-workers from University of Catanzaro “Magna Graecia” (article number 2000121) studied the anticancer effect of multidrug liposomes in breast cancer cells. The co-delivery of anticancer drugs (gemcitabine hydrochloride and paclitaxel) increased the anticancer effect of both drugs in vitro, inhibiting the tumor growth in an in vivo model of metastatic murine breast cancer and improved the overall survival of murine breast cancer metastatic model. Prof. Satchi-Fainaro and co-workers from Tel Aviv University (article number 2000124) provided an overview of drug delivery and novel therapeutic approaches to target GB. The authors firstly discussed the conventional and gold-standard treatments in GB, including surgical resection followed by chemotherapy and radiotherapy, and then the limitations of conventional treatment to achieve complete resection of the tumor, in the majority of GB patients due to the invasiveness of GB and the limitations of drug penetration across the BBB. The authors also reported a detailed overview of novel nanomedicines that can cross the BBB and specifically target the cancer cells to achieve a targeted treatment of GB. Moreover, Prof. Vicent and co-workers from Centro de Investigación Príncipe Felipe (article number 202000136) provided a detailed revision of literature on the current options for prostate cancer (PCa) treatment. The authors reported discussions in hormonal therapy, chemotherapy, immunotherapy, and radiotherapy, the reformulation of existing therapeutics as nanomedicines, and described the nanomedicine approaches to advanced PCa treatment under evaluation in both preclinical and clinical studies. The opportunity to improve the design of novel therapeutic approaches, the identification of novel functional biomarkers to stratify patients, and finally the guidelines for nanomedicine design were also discussed. In the field of cancer nanomedicine, Prof. Florindo and co-workers from Universidade de Lisboa (article number 2000147) discussed the nanomedicines and their impact in melanoma therapy. The authors addressed the current knowledge on melanoma biology and immunology, focusing on the emerging role of nanotechnology in the development of combinatorial strategies targeting and regulating the function of major players in melanoma progression and immune evasion. The impact of nanotechnology was also approached in cancer immunotherapy and the emergent-targeted nanomedicines for immunotherapy were also discussed for their relevance to melanoma genomics, predictive biomarkers, clinical trial design, and clinical regulation of nanomedicines. Furthermore, Prof. Cabral and co-workers from University of Tokyo (article number 2000159) provided an overview of clinical translation of self-assembled nanomedicines for anti-cancer therapy. In particular, the authors reported the process for designing nanomedicines to have a selective delivery of probes and anticancer agents to tumors, and thus, achieving an improved diagnostic or therapeutic efficacy, as well as relieving potential side effects. They also presented the current status of clinically used self-assembled nanomedicines, reviewing recent advances of nanomedicines in clinical trials, discussing the challenges and future perspectives of nanomedicines in the clinic. Prof. Sosnik and co-workers from Technion-Israel Institute of Technology (article number 2000010) investigated the potential of glycosylation to have an active targeting of nano-drug delivery systems for the treatment of solid tumors in patients overexpressing glucose transporters. Curcumin-loaded targeted micelles in the presence of glucose molecules on the surface of micelles lead to enhanced internalization of micelles inside breast cancer cells and increased the anticancer activity both in vitro and in vivo, in mice bearing 4T1-induced tumors. In the field of gene delivery, Prof. Shen and co-workers (article number 2000099) from Houston Methodist Research Institute provided an overview of mRNA-based therapeutics as platform for treatment of human diseases. Multiple nanotechnology-based delivery platforms for mRNA delivery were discussed, such as polymer-based polyplex, lipid-based lipoplex, and lipid-coated polymer-based lipopolyplex, and their applications in biotechnology, including cell reprogramming and gene editing, as well as the potential clinical translational in protein replacement therapy, infectious disease and anti-cancer therapy. Prof. Mitchell and co-workers from University of Pennsylvania (article number 2000111) discussed the potential use of nucleic acids, such as small interfering RNAs (siRNA) and antisense oligonucleotides, in gastrointestinal (GI) diseases. The authors described the use of lipid nanoparticles (LNPs) as an emerging delivery system that can protect nucleic acids from degradation, mediate their intracellular delivery and deliver intact siRNA and antisense oligonucleotides through the gastrointestinal barrier. Lipid compositions of LNPs enhance the delivery of nanosystems in the GI tract and improve the LNP-b-DNA delivery. Moreover, sequencing results and high-throughput in vivo screening indicated that LNPs accelerate the discovery of LNPs for GI tract nucleic acid delivery upon oral administration. In another work, Prof. Zhang and co-workers from Åbo Akademi University (article number 2000072) described the effective intracellular delivery of CRISPR/Cas9 plasmids for homology-directed repair by functionalization of mesoporous silica nanoparticles (MSNs). Functionalized MSNs, forming complexes with CRISPR/Cas9 plasmids, which can enhance the cellular internalization and endosomal escape, facilitating the nuclear transport of the CRISPR/Cas9 plasmids. CRISPR/Cas9 plasmids-functionalized MSNs were shown to aid the overcoming of physiological barriers, allowing the delivery through the GI tract and regulating the intracellular signaling of CRISPR/Cas9 plasmids. In the field of osteoarthritis, Prof. Duvall and co-workers from Vanderbilt University (article number 2000072) described an overview of the recent advances in clinical translation of intra-articular osteoarthritis (OA) and potential nanosystems that are currently used for its treatment. In particular, the authors reported the recent development of clinically tested therapies for OA, and highlighting the recent nanosystems, such as hydrogels, liposomes, polymeric microparticles and nanoparticles, drug conjugates, and combination systems that are currently in clinical trials and have had a significant impact in nanomedicine. In the topical drug delivery field, Prof. Chiappini and co-workers from King's College London (article number 2000160) provided an overview of nanodelivery systems to overcome physiological barriers and to guarantee the passage through the skin, mucosae, eyes and ears for target diseases and accumulation of drugs in specific tissues. In the field of anti-bacterial drug delivery, Prof. Zhou and co-workers from Zhejiang University (article number 2000107) demonstrated that a hydrogel based on photosynthetic microorganisms can enhance wound healing by production and local delivery of oxygen that is carried out to alleviate acute and chronic tissue hypoxia. The authors demonstrated that chlorophyll was released from spirulina platensis coated with carboxymethyl after being irradiated with a 650-nm laser, generating reactive oxygen species (ROS) and leading to photodynamic destruction of bacteria in the infectious area. In another paper, Prof. de la Fuente and co-workers from Instituto de Nanociencia y Materiales de Aragón (article number 2000113) highlighted the importance and progress of pulmonary administration, via passive and active targeting strategies towards bacteria reservoirs to overcome the challenges in tuberculosis treatment. In the field of anti-inflammatory drug delivery, Prof. Santos and co-workers from University of Helsinki (article number 2000058) described a nanocomposite, polydopamine-based nanoparticle, for anti-inflammatory delivery of budesonide encapsulated in a pH-responsive endosomolytic polymer, in order to prevent ROS production and acting as scavenger for inflammation. The authors demonstrated such nanocomposite led to successfully macrophage phenotype and switch from pro-inflammatory M1 to anti-inflammatory M2 macrophages. Overall, this special issue is expected to provide important background and new knowledge on the latest advances of nanomaterials/nanomedicines and their biomedical applications. The guest editors of this special issue are very grateful to all authors who accepted our invitation and contributed with their amazing works to this exciting issue on advanced nanosystems for clinical translation. This Special Issue is dedicated to the “1st International Northern-Southern Europe Workshop in Nanomedicine” hold in the city of Chieti (Abruzzi, Italy) in January 15–17, 2020, and to all the scientists working in the field of nanomedicine and other related fields. Finally, our special thanks go also to the editors and staff of Advanced Therapeutics for their continuous support for this special issue and for making this possible. Christian Celia is an Associate Professor in Pharmaceutical Technology and Advanced Drug Delivery at the University of Chieti – Pescara “. Christian Celia got his PharmD with residence in Hospital Pharmacy in 2008 at the University of Catanzaro and the PhD in Pharmaceutical Science in 2012 in the same institution. He spent two years as a visiting scholar at Houston Methodist Research Institute, Houston, Texas, USA in the Department of Nanomedicine where he rose to the position of Affiliated Scientist in 2012. In 2012, he joined the Department of Pharmacy at the University of Chieti – Pescara as an Assistant Professor and was promoted to Associate Professor in 2017. The research activity of Prof. Celia is focused on advanced drug delivery for anticancer therapy, cutaneous diseases and regenerative medicine. Donatella Paolino is Full Professor in Pharmaceutical Technology and Advanced Drug Delivery at the University Magna Graecia of Catanzaro. She got her PhD in Technology of bioactive substances in 2004 at the University of Palermo, and PharmD in Hospital Pharmacy at the University of Catania. Her teaching responsibilities are in undergraduate and PhD programs. Her scientific interests are design, preparation, characterization and evaluation, both in vitro and in vivo, of innovative colloidal drug delivery systems for the topical administration, (ophthalmic, dermal, transdermal, mucosal and transmucosal) of drugs. Hélder A. Santos obtained his Doctor of Science in Technology (Chemical Engineering) in 2007 from the Helsinki University of Technology (now Aalto University) in Finland. Currently, he is a Full Professor in Pharmaceutical Nanotechnology at the Faculty of Pharmacy, University of Helsinki, and Head of the Nanomedicines and Biomedical Engineering research group. His scientific expertise lies in the development of nanoparticles/nanomedicines for biomedical applications, particularly porous silicon and polymeric-based nanomaterials, for simultaneous controlled drug delivery, diagnostic, and therapy for cancer, diabetes, and cardiovascular diseases.

  • Research Article
  • Cite Count Icon 70
  • 10.1002/asia.201300142
Hierarchical Hollow Hydroxyapatite Microspheres: Microwave‐Assisted Rapid Synthesis by Using Pyridoxal‐5′‐Phosphate as a Phosphorus Source and Application in Drug Delivery
  • Apr 3, 2013
  • Chemistry – An Asian Journal
  • Xin‐Yu Zhao + 6 more

Three-dimensional (3D) hydroxyapatite (HAP) hierarchical nanostructures, in particular hollow nanostructures, have attracted much attention owing to their potential applications in many biomedical fields. Herein, we report a rapid microwave-assisted hydrothermal synthesis of a variety of hydroxyapatite hierarchical nanostructures that are constructed by the self-assembly of nanorods or nanosheets as the building blocks, including HAP nanorod-assembled hierarchical hollow microspheres (HA-NRHMs), HAP nanorod-assembled hierarchical microspheres (HA-NRMs), and HAP nanosheet-assembled hierarchical microspheres (HA-NSMs) by using biocompatible biomolecule pyridoxal-5'-phosphate (PLP) as a new organic phosphorus source. The PLP molecules hydrolyze to produce phosphate ions under microwave-hydrothermal conditions, and the phosphate ions react with calcium ions to form HAP nanorods or nanosheets; then, these nanorods or nanosheets self-assemble to form 3D HAP hierarchical nanostructures. The preparation method reported herein is time-saving, with microwave heating times as short as 5 min. The HA-NRHMs consist of HAP nanorods as the building units, with an average diameter of about 50 nm. The effects of the experimental conditions on the morphology and crystal phase of the products are investigated. The hydrolysis of PLP under microwave-hydrothermal conditions and the important role of PLP in the formation of 3D HAP hierarchical nanostructures are investigated and a possible formation mechanism is proposed. The products are explored for potential applications in protein adsorption and drug delivery. Our experimental results indicate that the HA-NRHMs have high drug/protein-loading capacity and sustained drug-release behavior. Thus, the as-prepared HA-NRHMs are promising for applications in drug delivery and protein adsorption.

  • Research Article
  • Cite Count Icon 15
  • 10.1093/rb/rbab012
Development of a modular, biocompatible thiolated gelatin microparticle platform for drug delivery and tissue engineering applications.
  • Feb 28, 2021
  • Regenerative biomaterials
  • Hannah A Pearce + 8 more

The field of biomaterials has advanced significantly in the past decade. With the growing need for high-throughput manufacturing and screening, the need for modular materials that enable streamlined fabrication and analysis of tissue engineering and drug delivery schema has emerged. Microparticles are a powerful platform that have demonstrated promise in enabling these technologies without the need to modify a bulk scaffold. This building block paradigm of using microparticles within larger scaffolds to control cell ratios, growth factors and drug release holds promise. Gelatin microparticles (GMPs) are a well-established platform for cell, drug and growth factor delivery. One of the challenges in using GMPs though is the limited ability to modify the gelatin post-fabrication. In the present work, we hypothesized that by thiolating gelatin before microparticle formation, a versatile platform would be created that preserves the cytocompatibility of gelatin, while enabling post-fabrication modification. The thiols were not found to significantly impact the physicochemical properties of the microparticles. Moreover, the thiolated GMPs were demonstrated to be a biocompatible and robust platform for mesenchymal stem cell attachment. Additionally, the thiolated particles were able to be covalently modified with a maleimide-bearing fluorescent dye and a peptide, demonstrating their promise as a modular platform for tissue engineering and drug delivery applications.

  • Research Article
  • Cite Count Icon 335
  • 10.2174/1381612821666151027153246
Ceramic Nanoparticles: Fabrication Methods and Applications in Drug Delivery.
  • Dec 7, 2015
  • Current Pharmaceutical Design
  • Shindu Thomas + 3 more

Ceramic nanoparticles are primarily made up of oxides, carbides, phosphates and carbonates of metals and metalloids such as calcium, titanium, silicon, etc. They have a wide range of applications due to a number of favourable properties, such as high heat resistance and chemical inertness. Out of all the areas of ceramic nanoparticles applications, biomedical field is the most explored one. In the biomedical field, ceramic nanoparticles are considered to be excellent carriers for drugs, genes, proteins, imaging agents etc. To be able to act as a good and successful drug delivery agent, various characteristics of nanoparticles need to be controlled, such as size range, surface properties, porosity, surface area to volume ratio, etc. In achieving these properties on the favourable side, the method of preparation and a good control over process variables play a key role. Choosing a suitable method to prepare nanoparticles, along with loading of significant amount of drug(s) leads to development of effective drug delivery systems which are being explored to a great extent. Ceramic nanoparticles have been successfully used as drug delivery systems against a number of diseases, such as bacterial infections, glaucoma, etc., and most widely, against cancer. This review gives a detailed account of commonly used methods for synthesising nanoparticles of various ceramic materials, along with an overview of their recent research status in the field of drug delivery.

  • Research Article
  • Cite Count Icon 1
  • 10.3389/conf.fbioe.2016.01.02364
Folic acid conjugated amine functionalized cerium oxide nanoparticle for cancer targeted gene therapy
  • Jan 1, 2016
  • Frontiers in Bioengineering and Biotechnology
  • Sarkar Kishor + 5 more

Event Abstract Back to Event Folic acid conjugated amine functionalized cerium oxide nanoparticle for cancer targeted gene therapy Kishor Sarkar1, Harini V. Krishnan1, G Vinoth Kumar2, K Suresh Babu2, Vinayak Sant1 and Shilpa Sant1, 3, 4 1 University of Pittsburgh, Department of Pharmaceutical Sciences, United States 2 Pondicherry University, Centre for Nano Science and Technology, India 3 University of Pittsburgh, Department of Bioengineering, United States 4 University of Pittsburgh, McGowan Institute for Regenerative Medicine, United States Introduction: Gene therapy has become alternative therapeutic approach to treat genetic diseases such as cancer[1]. Nonviral vectors have gained tremendous attraction over the viral vector due to its low toxicity, non-immunogenicity and low production cost[2]-[4]. Recently, rare earth metal oxide especially cerium oxide nanoparticle (CNP) has widely been used in biomedical fields such as drug delivery, bio-imaging, nanomedicine and tissue engineering application because of its inherent antioxidant activity, free radical scavenging activity and radioprotection to normal cell[5],[6]. It is also reported that CNP increased the ROS (reactive oxygen species) in cancer cell[7]. Therefore, we hypothesized that therapeutic gene (like siRNA, p53 etc.) delivery by means of CNP may give the dual therapeutic effect in conjugation with increased ROS level in cancer cell for the treatment of cancer. Here we report the functionalization of CNP by low molecular weight polyethyleneimine (LPEI, 2 kDa) followed by conjugation of folic acid (FA) for targeted gene delivery. Methods: LPEI was conjugated with CNP (LPEI-conj-CNP) through carboxylation followed by amidation reaction. Then, FA was reacted with LPEI-conj-CNP by carbodiimide to get FA-LPEI-conj- CNP. CNP/pDNA (enhanced green fluorescent protein, EGFP encoding pDNA) complexes were prepared at various weight ratios and characterized by agarose gel electrophoresis assay and dynamic light scattering (DLS). In vitro transfection efficiency, toxicity, ROS and underlying mechanistic pathway were also evaluated in HeLa cell. Results: Poor water dispersibility of CNP at physiological pH is a major drawback for biological field especially gene/ drug delivery application. CNP forms stable dispersion in acidic pH only. Despite the positive zeta potential of CNP, it did not bind any DNA at any weight ratio due to poor dispersibility. But, the DNA complexation capability of CNP significantly increased after conjugation of LPEI and LPEI-conj-CNP complexed all pDNA at a very low weight ratio of 0.5:1. Due to presence of lots of primary amine groups in LPEI, the water dispersibility of CNP increased drastically and resulted better DNA complexation through the cationic primary amine groups. The transfection efficiency of CNP increased after conjugation of LPEI but the efficiency increased significantly after FA conjugation with LPEI-conj-CNP. FA-LPEI-conj-CNP/pDNA complex at weight ratio of 15:1 showed highest transfection efficiency which also surpassed the efficiency offered by PEI (25 kDa) (Figure 1). It was also observed that FA-LPEI-conj-CNP internalized into cell via folate receptor as well as caveolae mediated pathway and resulted enhanced transfection efficiency. While LPEI-conj-CNP followed clathrin mediated pathway followed by lysosomal compartment entrapment and as a result showed low transfection efficiency. It was found that green fluorescence (fluorescent dichlorofluorescein, DCF obtained through oxidation of nonfluorescent dichlorofluorescein diacetate, DCFA by ROS) increased drastically by FA-LPEI-conj-CNP compared to all CNPs and H2O2 treated cell indicating the increase in ROS (Figure 2). Conclusion: The transfection efficiency as well as ROS of CNP increased after functionalization of CNP especially after FA conjugation. Therefore, FA-LPEI-conj-CNP may be useful candidate in nonviral gene therapy for cancer treatment by using its dual property including gene delivery and ROS enhancement. This work was financially supported by Start-up funds from University of Pittsburgh School of Pharmacy

  • Research Article
  • Cite Count Icon 276
  • 10.1016/j.jfda.2015.01.001
Formulation of essential oil-loaded chitosan–alginate nanocapsules
  • Mar 5, 2015
  • Journal of Food and Drug Analysis
  • Dheebika Natrajan + 3 more

Formulation of essential oil-loaded chitosan–alginate nanocapsules

  • Research Article
  • Cite Count Icon 1
  • 10.22270/ajdhs.v1i1.3
Dendrimers as Drug Delivery Carriers in the Dentistry
  • Dec 25, 2021
  • Asian Journal of Dental and Health Sciences
  • Sunil Kumar Prajapati + 8 more

This review gives concise information about the application of dendrimers as drug delivery carrier in the field of drug delivery. Due to their unique architecture these have improved physical and chemical properties. Due to their terminal groups these show high solubility, miscibility and reactivity. Dendrimers have well defined size, shape, molecular weight and monodispersity. These properties make the dendrimers a suitable carrier in drug delivery application. Dendrimers are unimolecular miceller in nature and due to this enhances the solubility of poorly soluble drugs. Their compatibility with DNA, heparin and polyanions make them more versatile. Dendrimers, also referred as modern day polymers, they offer much more good properties than the conventional polymers. Due to their multivalent and mono disperse character dendrimers have stimulated wide interest in the field of chemistry biology, drug delivery, gene therapy and chemotherapy. Self-assembly produces a faster means of generating nanoscopic functional and structural systems. But their actual utility in drug delivery can be assessed only after deep understanding of factors affecting their properties and their behaviour in vivo. Keywords: Dendrimers, Drug targeting, nanoscale carriers.

  • Research Article
  • 10.22270/ajdhs.v1i1.8
Development and Evaluation of Aceclofenac Liposomes
  • Dec 25, 2021
  • Asian Journal of Dental and Health Sciences
  • Gurleen Kaur + 3 more

This review gives concise information about the application of dendrimers as drug delivery carrier in the field of drug delivery. Due to their unique architecture these have improved physical and chemical properties. Due to their terminal groups these show high solubility, miscibility and reactivity. Dendrimers have well defined size, shape, molecular weight and monodispersity. These properties make the dendrimers a suitable carrier in drug delivery application. Dendrimers are unimolecular miceller in nature and due to this enhances the solubility of poorly soluble drugs. Their compatibility with DNA, heparin and polyanions make them more versatile. Dendrimers, also referred as modern day polymers, they offer much more good properties than the conventional polymers. Due to their multivalent and mono disperse character dendrimers have stimulated wide interest in the field of chemistry biology, drug delivery, gene therapy and chemotherapy. Self-assembly produces a faster means of generating nanoscopic functional and structural systems. But their actual utility in drug delivery can be assessed only after deep understanding of factors affecting their properties and their behaviour in vivo. Keywords: Dendrimers, Drug targeting, nanoscale carriers.

  • Research Article
  • Cite Count Icon 33
  • 10.1016/j.ijpharm.2024.124485
Cyclodextrin in drug delivery: Exploring scaffolds, properties, and cutting-edge applications
  • Jul 17, 2024
  • International Journal of Pharmaceutics
  • Parbeen Singh + 1 more

Cyclodextrin in drug delivery: Exploring scaffolds, properties, and cutting-edge applications

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