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Cell-responsive nanogels for anticancer drug delivery

Maciel, Dina Maria Sousa
Fonte: Universidade da Madeira Publicador: Universidade da Madeira
Tipo: Dissertação de Mestrado
Publicado em /09/2014 ENG
Relevância na Pesquisa
66.26%
One of the main goals in Nanomedicine is to create innovative drug delivery systems (DDS) capable of delivering drugs into a specific location with high efficiency. In the development of DDS, some essential properties are desired, such as biocompatibility and biodegradability. Furthermore, an ideal DDS should be able to deliver a drug in a controlled manner and minimize its side effects. These two objectives are still a challenge for researchers all around the world. Nanogels are an excellent vehicle to use in drug delivery and several other applications due to their biocompatibility. They are polymer-based networks, chemically or physically crosslinked, with at least 80-90% water in their composition. Their properties can be tuned, like the nanogel size, multifunctionality and degradability. Nanogels are capable of carrying in their interior bioactive molecules and deliver them into cells. The main objective of this project was to produce nanogels for the delivery of anticancer drugs with the ability of responding to existent stimuli inside cells (cellresponsiveness nanogels) and/or of controlled drug delivery. The nanogels were mainly based on alginate (AG), a natural biopolymer, and prepared using emulsion approaches. After their synthesis...

Colloidal carriers for ophthalmic drug delivery

Mainardes, R. M.; Urban, MCC; Cinto, P. O.; Khalil, N. M.; Chaud, M. V.; Evangelista, R. C.; Gremiao, MPD
Fonte: Bentham Science Publ Ltd Publicador: Bentham Science Publ Ltd
Tipo: Revisão Formato: 363-371
ENG
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To achieve effective drug concentration at the intended site for a sufficient period of time is a requisite desired for many drug formulations. For drugs intended to ocular delivery, its poor bioavailability is due to pre-corneal factors. Most ocular diseases are treated by topical drug application in the form of solution, suspension and ointment. However, such dosage forms are no longer sufficient to combat some ocular diseases. Intravitreal drug injection is the current therapy for disorders in posterior segment. The procedure is associated with a high risk of complications, particularly when frequent, repeated injections are required. Thus, sustained-release technologies are being proposed, and the benefits of using colloidal carriers in intravitreal injections are currently under investigation for posterior drug delivery. This review will discuss recent progress and specific development issues relating to colloidal drug delivery systems, such as liposomes, niosomes, nanoparticles, and microemulsions in ocular drug delivery.

Rheological, Mechanical and Adhesive Properties of Surfactant-Containing Systems Designed as a Potential Platform for Topical Drug Delivery

Carvalho, Flavia Chiva; Rocha e Silva, Hilris; da Luz, Gabriela Marielli; Barbi, Mariana da Silva; Landgraf, Daniele Silveira; Chiavacci, Leila Aparecida; Vitorino Sarmento, Victor Hugo; Daflon Gremiao, Maria Palmira
Fonte: Amer Scientific Publishers Publicador: Amer Scientific Publishers
Tipo: Artigo de Revista Científica Formato: 280-289
ENG
Relevância na Pesquisa
66.22%
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); In the last few decades, nanotechnology has led to an advance in the development of topical drug delivery. Nanostructured drug delivery systems enable the compartmentalization of drugs in restricted environments, modifying the release profile and maintaining the required drug concentration for prolonged periods at the site of action and/or absorption. The development of nanostructured systems containing surfactants has evolved rapidly. Mixtures of surfactant, oil and water can self-associate to form structures, such as microemulsions and liquid crystal phases, which can be exploited as drug delivery systems because their nanostructured organization can control drug release. Therefore, the purpose of this study was to assess the potential of systems containing polyoxypropylene (5) polyoxyethylene (20) cetyl ether as surfactant, oleic acid or mineral oil as the oily phase, and water to be used as a platform in the development of topical drug delivery systems. Physicochemical characterization of the systems was performed by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), rheological tests and texture profile analysis. The ternary phase diagrams showed that combinations of surfactant/mineral oil/water and surfactant/oleic acid/water could form various thermodynamically stable structures...

Controlled transscleral drug delivery formulations to the eye: establishing new concepts and paradigms in ocular anti-inflammatory therapeutics and antibacterial prophylaxis

Paganelli, Fernando; Cardillo, Jose A.; Dare, Alessandro R. J.; Melo, Luiz A. S.; Lucena, David R.; Silva, Arnobio A.; Oliveira, Anselmo Gomes de; Pizzolitto, Antonio C.; Lavinsky, Daniel; Skaf, Mirian; Souza-Filho, Acacio A.; Hofling-Lima, Ana L.; Nguyen
Fonte: Informa Healthcare Publicador: Informa Healthcare
Tipo: Artigo de Revista Científica Formato: 955-965
ENG
Relevância na Pesquisa
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Importance of the field: The use of topical agents poses unique and challenging hurdles for drug delivery. Topical steroids effectively control ocular inflammation, but are associated with the well-recognized dilemma of patient compliance. Although administration of topical antimicrobials as prophylaxis is acceptable among ophthalmologists, this common practice has no sound evidence base Developing a new antimicrobial agent or delivery strategy with enhanced penetration by considering the anatomical and physiological constraints exerted by the barriers of the eye is not a commonly perceived strategy. Exploiting the permeability of the sclera, subconjunctival routes may offer a promising alternative for enhanced drug delivery and tissue targeting.Area covered in this review: Ocular drug delivery strategies were reviewed for ocular inflammation and infections clinically adopted for newer class of antimicrobials, which use a multipronged approach to limit risks of endophthalmitis.What the reader will gain: The analysis substantiates a new transscleral drug delivery therapeutic approach for cataract surgery.Take home message: A new anti-inflammatory and anti-infective paradigm that frees the patient from the nuisance of topical therapeutics is introduced...

Liposomes and micro/nanoparticles as colloidal carriers for nasal drug delivery

Mainardes, Rubiana Mara; Cocenza Urban, Maria Cristina; Cinto, Priscila Oliveira; Chaud, Marco Vinícius; Evangelista, Raul Cesar; Daflon Gremião, Maria Palmira
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Revisão Formato: 275-285
ENG
Relevância na Pesquisa
66.31%
The use of the nasal route for drug delivery has attracted much interest in recent years in the pharmaceutical field. Local and principally systemic drug delivery can be achieved by this route of administration. But the nasal route of delivery is not applicable to all drugs. Polar drugs and some macromolecules are not absorbed in sufficient concentration due to poor membrane permeability, rapid clearance and enzymatic degradation into the nasal cavity. Thus, alternative means that help overcome these nasal barriers are currently in development. Absorption enhancers such as phospholipids and surfactants are constantly used, but care must be taken in relation to their concentration. Drug delivery systems including liposomes, cyclodextrins, micro- and nanoparticles are being investigated to increase the bioavailability of drugs delivered intranasally. This review article discusses recent progress and specific development issues relating to colloidal drug delivery systems in nasal drug delivery. © 2006 Bentham Science Publishers Ltd.

Development and in vitro evaluation of coated pellets containing chitosan to potential colonic drug delivery

Ferrari, Priscileila Colerato; Souza, Fagner Magalhães; Giorgetti, Leandro; Oliveira, Giselle Faria; Ferraz, Humberto Gomes; Chaud, Marco Vinícius; Evangelista, Raul Cesar
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 244-252
ENG
Relevância na Pesquisa
66.24%
In this work pellets containing chitosan for colonic drug delivery were developed. The influence of the polysaccharide in the pellets was evaluated by swelling, drug dissolution and intestinal permeation studies. Drug-loaded pellets containing chitosan as swellable polymer were coated with an inner layer of Kollicoat® SR 30 D and an outer layer of the enteric polymer Kollicoat® MAE 30 DP in a fluidized-bed apparatus. Metronidazole released from pellets was assessed using Bio-Dis dissolution method. Swelling, drug release and intestinal permeation were dependent on the chitosan and the coating composition. The drug release data fitted well with the Weibull equation, indicating that the drug release was controlled by diffusion, polymer relaxation and erosion occurring simultaneously. The film coating was found to be the main factor controlling the drug release and the chitosan controlling the drug intestinal permeation. Coated pellets containing chitosan show great potential as a system for drug delivery to the colon. © 2012 Elsevier Ltd.

Nanotechnology-based drug delivery systems for treatment of hyperproliferative skin diseases - a review

dos Santos, Fernanda Kolenyak; Oyafuso, Marcia Helena; Kiill, Charlene Priscila; Daflon-Gremião, Maria Palmira; Chorilli, Marlus
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 159-167
ENG
Relevância na Pesquisa
66.27%
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); The chronic hyperproliferative diseases (CHD) include cancer, precancerous lesions and diseases of unknown etiology such as psoriasis. Various drugs have been used in the treatment of CHD, such as antiproliferative and corticosteroids in general. However, some drugs have properties that limit their effectiveness, such as low solubility in water and low penetration of the skin. Thus, the control of drug release in the skin may improve efficacy and reduce side effects of many drugs used in hyperproliferative diseases. The purpose of this study was to make a systematic review of nanotechnology-based drug delivery systems used against hyperproliferative skin diseases. © 2013 Bentham Science Publishers.

Nanoparticle-based drug delivery systems: promising approaches against infections

Ranghar,Shweta; Sirohi,Parul; Verma,Pritam; Agarwal,Vishnu
Fonte: Instituto de Tecnologia do Paraná - Tecpar Publicador: Instituto de Tecnologia do Paraná - Tecpar
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/04/2014 EN
Relevância na Pesquisa
66.21%
Despite the fact that many new drugs and technologies have been developed to combat the infectious diseases, these have continued to be global health challenges. The use of conventional antimicrobial agents against these infections is always associated with problems such as the development of multiple drug resistance and adverse side effects. In addition, the inefficient traditional drug delivery system results in inadequate therapeutic index, low bioavailability of drugs and many other limitations. In this regard, antimicrobial nanoparticles and nanosized drug delivery carriers have emerged as potent effective agents against the infections. Nanoparticles have unique properties owing to their ultra small and controllable size such as high surface area, enhanced reactivity, and functionalizable structure. This review focused on different classes of antimicrobial nanoparticles, including metal, metal oxide and others along with their mechanism of action and their potential use against the infections. The review also focused on the development of nanoparticle systems for antimicrobial drug delivery and use of these systems for delivery of various antimicrobial agents, giving an overview about modern nanoparticle based therapeutic strategies against the infections.

Vaginal Drug Delivery Systems for HIV Prevention

Rohan, Lisa Cencia; Sassi, Alexandra B.
Fonte: Springer US Publicador: Springer US
Tipo: Artigo de Revista Científica
Publicado em 05/02/2009 EN
Relevância na Pesquisa
66.2%
Microbicides have become a principal focus for HIV prevention strategies. The successful design of drug delivery systems for vaginal microbicide drug candidates brings with it a multitude of challenges. It is imperative that the chemical and physical characteristics of the drug candidate and its mechanism of action be clearly understood and considered to successfully deliver and target drug candidates efficiently. In addition, an understanding of the dynamic nature of the vaginal environment, the tissue and innate barriers present, as well as patient preferences are critical considerations in the design of effective microbicide products. Although the majority of drug candidates clinically evaluated to date have been delivered using conventional semisolid aqueous-based gel dosage forms, drug delivery system design has recently been extended to include advanced delivery systems such as vaginal rings, quick-dissolve films, and tablets. Ultimately, it may be necessary to develop multiple dosage platforms for a single active agent to provide users with options that can be used within the constraints of their social environment, personal choice, and environmental conditions.

Near Infrared-Sensitive Nanoparticles for Targeted Drug Delivery

Tan, Mei Chee; Ying, Jackie Y.; Chow, Gan-Moog
Fonte: MIT - Massachusetts Institute of Technology Publicador: MIT - Massachusetts Institute of Technology
Tipo: Artigo de Revista Científica Formato: 21455 bytes; application/pdf
EN_US
Relevância na Pesquisa
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The invasive nature and undesirable side-effects related to conventional cancer therapy, such as surgery and chemotherapy, have led to the development of novel drug delivery systems (DDS). A minimally invasive DDS using near-infrared (NIR) light as a trigger for drug release is investigated to reduce the adverse side-effects triggered by systemic delivery of chemotherapeutic drugs. The low tissue absorbance in the NIR region, λ = 650–2500 nm, allows the irradiation to penetrate through tissues to release cisplatin from a NIR-sensitive nanocomposite of Au-Au₂S. Our laboratory has recently shown that cisplatin can be effectively released from Au-Au₂S upon NIR irradiation. Cisplatin was loaded onto Au-Au₂S through its adsorption on COOH-functionalized alkanethiols coated on Au-Au₂S. The current work focuses on the development of methods to control the release of cisplatin. Drug release is controlled by either the irradiation parameters or the type of coatings. The effect of different coatings on NIR sensitivity and drug release is investigated. Molecular layers of HS-(CH₂)n-COOH and HS-CH₂-COO-CH₂(CH₂CH₂O)xCH₂-COOH have been successfully coated onto Au-Au₂S. The effect of different surface layers on drug adsorption is being examined. In addition...

Bionano Electronics: Magneto-Electric Nanoparticles for Drug Delivery, Brain Stimulation and Imaging Applications

Guduru, Rakesh
Fonte: FIU Digital Commons Publicador: FIU Digital Commons
Tipo: Artigo de Revista Científica Formato: application/pdf
Relevância na Pesquisa
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Nanoparticles are often considered as efficient drug delivery vehicles for precisely dispensing the therapeutic payloads specifically to the diseased sites in the patient’s body, thereby minimizing the toxic side effects of the payloads on the healthy tissue. However, the fundamental physics that underlies the nanoparticles’ intrinsic interaction with the surrounding cells is inadequately elucidated. The ability of the nanoparticles to precisely control the release of its payloads externally (on-demand) without depending on the physiological conditions of the target sites has the potential to enable patient- and disease-specific nanomedicine, also known as Personalized NanoMedicine (PNM). In this dissertation, magneto-electric nanoparticles (MENs) were utilized for the first time to enable important functions, such as (i) field-controlled high-efficacy dissipation-free targeted drug delivery system and on-demand release at the sub-cellular level, (ii) non-invasive energy-efficient stimulation of deep brain tissue at body temperature, and (iii) a high-sensitivity contrasting agent to map the neuronal activity in the brain non-invasively. First, this dissertation specifically focuses on using MENs as energy-efficient and dissipation-free field-controlled nano-vehicle for targeted delivery and on-demand release of a anti-cancer Paclitaxel (Taxol) drug and a anti-HIV AZT 5’-triphosphate (AZTTP) drug from 30-nm MENs (CoFe2O4-BaTiO3) by applying low-energy DC and low-frequency (below 1000 Hz) AC fields to separate the functions of delivery and release...

Graphene and graphene oxide as new nanocarriers for drug delivery applications

Liu, J.; Cui, L.; Losic, D.
Fonte: Elsevier BV Publicador: Elsevier BV
Tipo: Artigo de Revista Científica
Publicado em //2013 EN
Relevância na Pesquisa
66.22%
The biomedical applications of graphene-based materials, including drug delivery, have grown rapidly in the past few years. Graphene and graphene oxide have been extensively explored as some of the most promising biomaterials for biomedical applications due to their unique properties: two-dimensional planar structure, large surface area, chemical and mechanical stability, superb conductivity and good biocompatibility. These properties result in promising applications for the design of advanced drug delivery systems and delivery of a broad range of therapeutics. In this review we present an overview of recent advances in this field of research. We briefly describe current methods for the surface modification of graphene-based nanocarriers, their biocompatibility and toxicity, followed by a summary of the most appealing examples demonstrated for the delivery of anti-cancer drugs and genes. Additionally, new drug delivery concepts based on controlling mechanisms, including targeting and stimulation with pH, chemical interactions, thermal, photo- and magnetic induction, are discussed. Finally the review is summarized, with a brief conclusion of future prospects and challenges in this field.; Jingquan Liu, Liang Cui, Dusan Losic

Silica materials in drug delivery applications

Simovic, S.; Ghouchi-Eskandar, N.; Sinn, A.; Losic, D.; Prestidge, C.
Fonte: Bentham Science Publishers Publicador: Bentham Science Publishers
Tipo: Artigo de Revista Científica
Publicado em //2011 EN
Relevância na Pesquisa
66.28%
In this review article we collect and analyse preparation, chemistry and properties of silica materials relevant for drug delivery applications. We review some of the most relevant milestones in the research of silica materials for implantable, oral, intravenous and dermal drug delivery systems. Preparation, chemistry and drug delivery characteristics of fumed silica nanoparticles (oral and dermal delivery route), silica xerogels (implant delivery), mesoporous silica materials (implant and oral delivery) and mesoporous silica spheres (intravenous delivery) with particular emphasis on their role in anticancer therapy and the design of stimuli responsive drug delivery systems are analysed. Recent progress in the research of silica materials for controlled drug delivery, namely, biocompatibility aspects, research on hybrid materials, anticancer and stimuli-responsive mesoporous silica materials are particularly emphasized.; Spomenka Simovic, Nasrin Ghouchi-Eskandar, Aw Moom Sinn, Dusan Losic and Clive A. Prestidge

Pickering-Emulsionen als Basis Lipid-basierter oraler Drug Delivery Systeme mit veränderter Wirkstofffreisetzung

Ellermann, Angelika
Fonte: Universität Tübingen Publicador: Universität Tübingen
Tipo: Dissertation; info:eu-repo/semantics/doctoralThesis
DE
Relevância na Pesquisa
66.2%
Die vorgelegte Arbeit setzt sich mit dem Einfluss des Polymerzusatzes auf Lipid basierte orale Drug Delivery Systeme auseinander. Um die Freisetzung aus Arzneiformen zu modifizieren, können Polymerdispersionen als Filmbildner eingesetzt werden. Da die Wirkstofffreisetzung, der zu entwickelnden Systeme, modifiziert werden sollte, wurde zum einen untersucht, welchen Einfluss verschiedene funktionale Polymerdispersionen auf die Stabilität von feststoffstabilisierten Emulsionen ausüben. Hierbei konnte gezeigt werden, dass es Polymerdispersionen gibt, die die Stabilität des Gesamtsystems nicht beeinflussen, solche, die sie nur leicht beeinflussen und andere, die die Stabilität stark beeinträchtigen. Durch Messungen des Zetapotentials konnte aufgeklärt werden, weshalb einige Mischungen kompatibel sind und andere hingegen nicht. Zur Verbesserung der Kompatibilität sind vor allem die verschiedenen Stabilisierungsmechanismen für Dispersionen von Bedeutung. Einerseits kann durch den Zusatz von Polysorbat 80 eine sterische Stabilisierung für die Mischungen aus einer Pickering-Emulsion und der Polymerdispersion Kollicoat SR 30 D oder Eudragit NE 30 D erreicht werden. Andererseits kann durch vorheriges Mischen der Polymerdispersion Eudragit RL 30 D mit der Pickering-Emulsion die Kompatibilität der Polymerdispersion Eudragit NE 30 D verbessert werden...

Composite polymer-bioceramic scaffolds with drug delivery capability for bone tissue engineering

Mouriño, Viviana Silvia Lourdes; Cattalini, Juan Pablo; Roether, J.; Dubey, P.; Roy, I.; Boccaccini, A. R.
Fonte: Informa Healthcare Publicador: Informa Healthcare
Tipo: info:eu-repo/semantics/article; info:ar-repo/semantics/artículo; info:eu-repo/semantics/publishedVersion Formato: application/pdf
ENG
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Next-generation scaffolds for bone tissue engineering (BTE) should exhibit the appropriate combination of mechanical support and morphological guidance for cell proliferation and attachment while at the same time serving as matrices for sustained delivery of therapeutic drugs and/or biomolecular signals, such as growth factors. Drug delivery from BTE scaffolds to induce the formation of functional tissues, which may need to vary temporally and spatially, represents a versatile approach to manipulating the local environment for directing cell function and/or to treat common bone diseases or local infection. In addition, drug delivery from BTE is proposed to either increase the expression of tissue inductive factors or to block the expression of others factors that could inhibit bone tissue formation. Composite scaffolds which combine biopolymers and bioactive ceramics in mechanically competent 3D structures, including also organic--inorganic hybrids, are being widely developed for BTE, where the affinity and interaction between biomaterials and therapeutic drugs or biomolecular signals play a decisive role in controlling the release rate.This review covers current developments and applications of 3D composite scaffolds for BTE which exhibit the added capability of controlled delivery of therapeutic drugs or growth factors. A summary of drugs and biomolecules incorporated in composite scaffolds and approaches developed to combine biopolymers and bioceramics in composites for drug delivery systems for BTE is presented. Special attention is given to identify the main challenges and unmet needs of current designs and technologies for developing such multifunctional 3D composite scaffolds for BTE. One of the major challenges for developing composite scaffolds for BTE is the incorporation of a drug delivery function of sufficient complexity to be able to induce the release patterns that may be necessary for effective osseointegration...

Polymer processing using supercritical fluid based technologies for drug delivery and tissue engineering applications

Duarte, Ana Rita C.; Mano, J. F.; Reis, R. L.
Fonte: Pan Stanford Publishing Publicador: Pan Stanford Publishing
Tipo: Parte de Livro
Publicado em /10/2015 ENG
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66.25%
From the use of botanical plants in early human civilizations through synthetic chemistry and biotechnology, drug research has always passionate scientists creating exciting challenges to a large number of researchers from different fields, thus, promoting a collaborative effort between polymer scientists, pharmacologists, engineers, chemists and medical researchers. Worldwide, there is an increasing concern on health care that creates a major opportunity for development of new pharmaceutical formulations. Ageing populations worried about the quality of life in the older years are actively seeking for new, more effective and patient compliant drug delivery devices. This has been the driving force for the continuous growth of the research made on delivery devices, which has become a powerful technique in health care. It has been recognized for long that simple pills or injections may not be the suitable methods of administration of a certain active compound. These medications present several problems and/or limitations, like poor drug bioavailability and systemic toxicity, derived essentially from pharmacokinetic and other carrier limitations and low solubility of the drugs in water. Therefore and to overcome these drawbacks, clinicians recommend frequent drug dosing...

Supercritical impregnation of polymer matrices spatially confined in microcontainers for oral drug delivery: Effect of temperature, pressure and time

Marizza, P.; Pontoni, L.; Rindzecicius, T.; Alopaeus, J. F.; Su, K.; Zeitler, J. Axel; Keller, S. S.; Kikic, I.; Moneghini, M.; De Zordi, N.; Solinas, D.; Cortesi, A.; Boisen, A.
Fonte: Elsevier Publicador: Elsevier
Tipo: Article; published version
EN
Relevância na Pesquisa
66.2%
This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.supflu.2015.08.023; The present study is aimed to enhance the oral bioavailability of ketoprofen by inserting it into the matrix of poly(vinylpyrrolidone) (PVP) K10 spatially confined into microcontainers, by means of supercritical CO2-aided impregnation. Microcontainers are cylindrical reservoirs, with typical sizes in the micrometer range, with a cavity open on one side, where the drug formulation is loaded. Differently to traditional tablets, microcontainers have a higher surface area per unit volume, and release the drug only in one direction. This design is meant to enhance the absorption of problematic drugs, like those with poor solubility in water. In a previous study we introduced a novel technique for drug loading of microcontainers, based on inkjet printing and supercritical impregnation (SCI). We showed that SCI produces accurate and reproducible drug loading for large arrays of microcontainers. In the attempt of enhancing the throughput of the loading methods, we propose the replacement of polymer inkjet printing with an easier manual compression of the PVP powder into the microcontainers. As the second step, the polymer powder filled-microcontainers were submitted to SCI. The separate role of different impregnation parameters (temperature...

Liposomal Drug Delivery Mediated by MR-guided High Intensity Focused Ultrasound: Drug Dose Painting and Influence of Local Tissue Transport Parameters

Yarmolenko, Pavel Sergeyevich
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação
Publicado em //2014
Relevância na Pesquisa
66.31%

Use of chemotherapeutics in treatment of solid tumors suffers from insufficient and heterogeneous drug delivery, systemic toxicity and lack of knowledge of delivered drug concentration. The overall objectives of this work were: 1) to address these shortcomings through development and characterization of a treatment system capable of real-time spatiotemporal control of drug distribution and 2) to investigate the role of MR-image-able tissue transport parameters in predicting drug distribution following hyperthermia-triggered drug release from nanoparticles. Towards these objectives, a combination of potentially synergetic technologies was used: 1) image-able low temperature-sensitive liposomes (iLTSLs) for drug delivery, 2) quantitative drug delivery and transport parameter imaging with magnetic resonance imaging (MRI), and 3) control over drug release with magnetic resonance-guided high intensity focused ultrasound (MR-HIFU). The overall hypothesis of this work is that the drug distribution in the targeted zone spatially correlates with the image-able transport-related parameters as well as contrast enhancement due to release of contrast agent during treatment.

We began by developing and characterizing iLTSLs, which were designed using a lipid formulation similar to one that is in clinical trials in the US (ThermoDox®) and a gadolinium-based MR contrast agent that is in widespread clinical use (Prohance®) and least likelihood of toxicity due to nephrogenic systemic fibrosis (NSF). The resulting liposome was found to stably encapsulate both an anthracycline chemotherapeutic...

Drug Delivery and Anti-Vascular Effects of Temperature Sensitive Liposomal Doxorubicin

Manzoor, Ashley Anne
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação
Publicado em //2010
Relevância na Pesquisa
66.34%

Traditionally, the goal of nanoparticle-based chemotherapy has been to decrease normal tissue toxicity by improving drug specificity to tumor. Relying on the EPR effect (Enhanced Permeability and Retention), a host of nanoparticles (from micelles and dendrimers to liposomes and lipidic nanoparticles) have been developed and tested for passive accumulation into tumor interstitium. Unfortunately, most nanoparticles achieve only suboptimal drug delivery to tumors, due to heterogeneity of tumor vessel permeability, limited nanoparticle penetration, and relatively slow drug release. However, recent developments in nanoparticle technology have occurred with the design and testing of a fast drug-releasing liposome triggered by local heat. This temperature-sensitive liposome formulation loaded with doxorubicin (Dox-TSL) has already shown substantial anti-tumor efficacy and is currently in clinical trials.

Previous pre-clinical work to understand the mechanism of efficacy has illustrated increases in overall drug concentration in the tumor, and an anti-vascular effect not observed with heat alone. These initial studies have also suggested that these liposomes may be the most efficacious when they are injected into a pre-heated tumor...

Initial Observations of Cell-Mediated Drug Delivery to the Deep Lung

Glaum, M.; Kumar, Arun (Professor); El-Badri, N.; Mohapatra, S.; Haller, E.; Park, S.; Patrick, L.; Nattkemper, L.; Vo, D.; Cameron, D. F.
Fonte: Cognizant Communication Corporation Publicador: Cognizant Communication Corporation
Tipo: Artigo de Revista Científica
ENGLISH (UNITED STATES)
Relevância na Pesquisa
66.21%
Final published version; Using current methodologies, drug delivery to small airways, terminal bronchioles, and alveoli (deep lung) is inefficient, especially to the lower lungs. Urgent lung pathologies such as acute respiratory distress syndrome (ARDS) and post-lung transplantation complications are difficult to treat, in part due to the methodological limitations in targeting the deep lung with high efficiency drug distribution to the site of pathology. To overcome drug delivery limitations inhibiting the optimization of deep lung therapy, isolated rat Sertoli cells preloaded with chitosan nanoparticles were use to obtain a high-density distribution and concentration (92%) of the nanoparticles in the lungs of mice by way of the peripheral venous vasculature rather than the more commonly used pulmonary route. Additionally, Sertoli cells were preloaded with chitosan nanoparticles coupled with the anti-inflammatory compound curcumin and then injected intravenously into control or experimental mice with deep lung inflammation. By 24 h postinjection, most of the curcumin load ( 90%) delivered in the injected Sertoli cells was present and distributed throughout the lungs, including the perialveloar sac area in the lower lungs. This was based on the high-density...