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Design of polymeric nanoparticles and its applications as drug delivery systems for acne treatment

Reis, C. P.; Martinho, N.; Rosado, C.; Fernandes, A. S.; Roberto, A.
Fonte: Drug Development and Industrial Pharmacy Publicador: Drug Development and Industrial Pharmacy
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
99.23699%
Objective: The aim of this study was to evaluate a formulation made of poly(lactide-co-glycolide) (PLGA) nanoparticles containing azelaic acid for potential acne treatment. Methods: Azelaic acid-loaded PLGA nanoparticles were prepared by spontaneous emulsification processes using poloxamer 188 as stabilizer. Several manufacturing parameters such as stirring rate, concentration of stabilizer and different recovery methods were investigated. Nanoparticles were evaluated in terms of size, zeta potential, encapsulation efficiency, release kinetics and permeation kinetics in vitro. Furthermore, in vitro toxicological studies were performed in Saccharomyces cerevisiae model. Results: The results showed that by adjusting some formulation conditions it was possible to obtain nanoparticles with high loading and a controlled drug release. Freeze-dried recovery altered the nanoparticles structure by enhancing porous structures and mannitol was required to control the mean particle size. The centrifugation recovery was found to be the best approach to nanoparticles recovery. Similar toxicity profiles were observed for both drug-free and azelaic acid-loaded nanoparticles, with concentration-dependent decreases in cell viability. Conclusion: These results indicate a potential formulation for controlled release delivery of azelaic acid to the follicular unit.

Metronidazole release using natural rubber latex as matrix

HERCULANO, Rondinelli Donizetti; GUIMARÃES, Sérgio Augusto Catanzaro; BELMONTE, Gustavo Campos; DUARTE, Marco Antonio Hungaro; Oliveira Junior , Osvaldo Novais de; KINOSHITA, Angela; GRAEFF, Carlos Frederico de Oliveira
Fonte: ABM, ABC, ABPol Publicador: ABM, ABC, ABPol
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
78.831543%
Natural Rubber Latex (NRL) can be used successfully in controlled release drug delivery due to their excellent matrix forming properties. Recently, NRL has shown to stimulate angiogenesis, cellular adhesion and the formation of extracellular matrix, promoting the replacement and regeneration of tissue. A dermatological delivery system comprising a topically acceptable, inert support impregnated with a metronidazole (MET) solution was developed. MET 2-(2- methyl- 5-nitro- 1H- imidazol- 1-yl) ethanol, has been widely used for the treatment of protozoa and anaerobic bacterial infections. MET is a nitroimidazole anti-infective medication used mainly in the treatment of infections caused by susceptible organisms, particularly anaerobic bacteria and protozoa. In a previous study, we have tested NRL as an occlusive membrane for GBR with promising results. One possible way to decrease the inflammatory process, it was incorporated the MET in NRL. MET was incorporated into the NRL, by mixing it in solution for in vitro protein delivery experiments. The solutions of latex and MET were polymerized at different temperatures, from -100 to 40 °C, in order to control the membrane morphology. SEM microscopy analysis showed that the number, size and distribution of pores in NRL membranes varied depending on polymerization temperature...

Development and In Vitro Evaluation of Propranolol Hydrochloride Controlled Release Tablets Using HPMC as Matrix Former

VILLANOVA, Janaina C. O.; CONSIGLIERI, Vladi O.
Fonte: COLEGIO FARMACEUTICOS PROVINCIA DE BUENOS AIRES Publicador: COLEGIO FARMACEUTICOS PROVINCIA DE BUENOS AIRES
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
69.209224%
The purpose of this paper was to produce controlled-release matrices with 120 mg of propranolol hydrochloride (PHCl) employing hydroxypropyl methylcellulose (HPMC, Methocel (R) K100) as the gel forming barrier. Although this class of polymers has been commonly used for direct compression, with the intent of use reduced polymer concentrations to achieve controlled drug release, in this study tablets were produced by the wet granulation process. HPMC percentages ranged from 15-34 % and both soluble and non soluble diluents were tested in the 10 proposed tablet compositions. Dissolution testing of matrices was performed over a 12 h period in 1.2 pH medium (the first 2 h) and in pH 6.8 (10 h). Dissolution kinetic analysis was performed by applying Zero-order, First-order and Higuchi models with the aim of elucidating the drug release mechanism. All physical-chemical characteristics such as average weight, friability, hardness, diameter, height, and drug content were in accordance to the pharmacopeial specifications. Taking into account that PHCl is a very soluble drug, low concentrations (15 %) of HPMC were sufficient to reduce the drug release and to promote controlled release of PHCl, presenting good dissolution efficiencies, between 50 % and 63 %. The Higuchi model has presented the best fit to the 15 % HPMC formulations...

Metronidazole release using natural rubber latex as matrix

Herculano, Rondinelli Donizetti; Guimarães, Sérgio Augusto Catanzaro; Belmonte, Gustavo Campos; Duarte, Marco Antonio Hungaro; Oliveira Júnior, Osvaldo Novais de; Kinoshita, Angela; Graeff, Carlos Frederico de Oliveira
Fonte: ABM, ABC, ABPol Publicador: ABM, ABC, ABPol
Tipo: Artigo de Revista Científica Formato: 57-61
ENG
Relevância na Pesquisa
78.831543%
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); Natural Rubber Latex (NRL) can be used successfully in controlled release drug delivery due to their excellent matrix forming properties. Recently, NRL has shown to stimulate angiogenesis, cellular adhesion and the formation of extracellular matrix, promoting the replacement and regeneration of tissue. A dermatological delivery system comprising a topically acceptable, inert support impregnated with a metronidazole (MET) solution was developed. MET 2-(2- methyl- 5-nitro- 1H- imidazol- 1-yl) ethanol, has been widely used for the treatment of protozoa and anaerobic bacterial infections. MET is a nitroimidazole anti-infective medication used mainly in the treatment of infections caused by susceptible organisms, particularly anaerobic bacteria and protozoa. In a previous study, we have tested NRL as an occlusive membrane for GBR with promising results. One possible way to decrease the inflammatory process, it was incorporated the MET in NRL. MET was incorporated into the NRL, by mixing it in solution for in vitro protein delivery experiments. The solutions of latex and MET were polymerized at different temperatures...

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
69.248716%
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.

Sílicas e carbonos mesoestruturados organofuncionalizados e aplicação à liberação controlada de fármacos; Mesostructured organofunctionalized silicas and carbons and application to controlled release drug delivery

Ramon Kenned de Sousa Almeida
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 27/08/2012 PT
Relevância na Pesquisa
99.02761%
As sílicas mesoporosas SBA-15 e SBA-16 sintetizadas através do método hidrotérmico com os copolímeros direcionadores de estrutura P123 e F127 foram organofuncionalizadas com agentes sililantes que contêm grupos funcionais, como nitrogênio, oxigênio e enxofre. As sílicas foram caracterizadas por análise elementar, espectroscopia na região do infravermelho, ressonância magnética nuclear de carbono e silício no estado sólido, termogravimetria, área superficial, espalhamento de raios X a baixo ângulo, microscopia eletrônicas de varredura e transmissão. As caracterizações comprovam a efetivação das sínteses das sílicas SBA-15 e SBA-16 com estruturas hexagonal e cúbica, respectivamente. As sílicas organofuncionalizadas, mostraram maiores graus de ancoramento obtido quando funcionalizadas com organossilanos contendo nitrogênio. Além das sílicas, foram sintetizados carbonos mesoporosos usando as sílicas como direcionadores rígidos de estrutura. Os mesmos foram funcionalizados com anidrido malêico e subsequentes reações com água e hidreto de alumínio e lítio resultando em grupos carboxílicos e na redução dos mesmos, respectivamente. A efetividade da funcionalização foi comprovada, sobretudo por espectroscopia na região do infravermelho...

Phosphorous containing chitosan beads for controlled oral drug delivery

Jayakumar, R.; Reis, R. L.; Mano, J. F.
Fonte: Universidade do Minho Publicador: Universidade do Minho
Tipo: Artigo de Revista Científica
Publicado em //2006 POR
Relevância na Pesquisa
79.3856%
Phosphorous containing chitosan (PCTS) was synthesized by a graft copolymerization technique in order to be used as controlled drug delivery devices. To test this potential, PCTS beads were prepared by using tripolyphosphate, at pH 4.0 and characterized by scanning electron microscopy. The in vitro drug release behavior in various pH solutions was studied using indomethacin (IM) as a model drug at two different concentrations (0.3 and 0.6% w/w). The release percent of IM from PCTS beads was found to be increased with the increasing of pH in the buffer solution. The release rate of IM at pH 7.4 was higher than that at pH 1.4, due to the ionization of phosphorous groups and the high solubility of IM in the alkaline medium. These results indicated that PCTS beads have the potential to be used as controlled drug delivery systems through oral administration by avoiding the drug release in the highly acidic gastric fluid region of the stomach.

Metronidazole release using natural rubber latex as matrix

Herculano,Rondinelli Donizetti; Guimarães,Sérgio Augusto Catanzaro; Belmonte,Gustavo Campos; Duarte,Marco Antonio Hungaro; Oliveira Júnior,Osvaldo Novais de; Kinoshita,Angela; Graeff,Carlos Frederico de Oliveira
Fonte: ABM, ABC, ABPol Publicador: ABM, ABC, ABPol
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/03/2010 EN
Relevância na Pesquisa
78.831543%
Natural Rubber Latex (NRL) can be used successfully in controlled release drug delivery due to their excellent matrix forming properties. Recently, NRL has shown to stimulate angiogenesis, cellular adhesion and the formation of extracellular matrix, promoting the replacement and regeneration of tissue. A dermatological delivery system comprising a topically acceptable, inert support impregnated with a metronidazole (MET) solution was developed. MET 2-(2- methyl- 5-nitro- 1H- imidazol- 1-yl) ethanol, has been widely used for the treatment of protozoa and anaerobic bacterial infections. MET is a nitroimidazole anti-infective medication used mainly in the treatment of infections caused by susceptible organisms, particularly anaerobic bacteria and protozoa. In a previous study, we have tested NRL as an occlusive membrane for GBR with promising results. One possible way to decrease the inflammatory process, it was incorporated the MET in NRL. MET was incorporated into the NRL, by mixing it in solution for in vitro protein delivery experiments. The solutions of latex and MET were polymerized at different temperatures, from -100 to 40 °C, in order to control the membrane morphology. SEM microscopy analysis showed that the number, size and distribution of pores in NRL membranes varied depending on polymerization temperature...

Microencapsulation: A promising technique for controlled drug delivery

Singh, M.N.; Hemant, K.S.Y.; Ram, M.; Shivakumar, H.G.
Fonte: Medknow Publications Publicador: Medknow Publications
Tipo: Artigo de Revista Científica
Publicado em //2010 EN
Relevância na Pesquisa
69.86912%
Microparticles offer various significant advantages as drug delivery systems, including: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery...

An Oral-Controlled Release Drug Delivery System for Liquid and Semisolid Drug Formulations

Haznar-Garbacz, Dorota; Garbacz, Grzegorz; Eisenächer, Friederike; Klein, Sandra; Weitschies, Werner
Fonte: Springer US Publicador: Springer US
Tipo: Artigo de Revista Científica
Publicado em 15/09/2011 EN
Relevância na Pesquisa
69.42661%
A novel oral drug delivery system for the controlled release of liquid drugs, drug solutions, and semisolid drug preparations is presented that is utilizing the constant vapor pressure of liquefied gas. The system is equipped with a capillary as an element determining the drug delivery rate and contains a liquefied propellant with a suitable boiling point below human body temperature. In the dissolution studies, polyacrylate gels of different viscosities containing paracetamol as model drug were used. Zero-order release kinetics was obtained. The release rates were dependent on the gel viscosity. Besides, by gel viscosity, the drug release rates could also be modified by changing the propellant type and the capillary parameters such as length or diameter. Accordingly, the new system enables a wide range of drug delivery kinetics which can be modified in a case-by-case basis in order to match the desired drug delivery characteristics.

Digital Drug Delivery: On-Off Ultrasound Controlled Antibiotic Release from Coated Matrices with Negligible Background Leaching

Noble, Misty L.; Mourad, Pierre D.; Ratner, Buddy D.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
69.247783%
Hydrogels, such as crosslinked poly(2-hydroxyethyl methacrylate) (pHEMA) have been used extensively in controlled release drug delivery systems. Our previous work demonstrated an ultrasound (US)-responsive system based on pHEMA coated with a self-assembled multilayer of C12-C18 methylene chains. The resulting coating was predominantly crystalline and relatively impermeable, forming an US-activated switch that controlled drug release on-demand, and kept the drug within the matrix in the absence of US. The device, as developed did, however, show a low background drug-leaching rate independent of US irradiation. For some applications, it is desirable to have very low or zero background release rates. This was achieved here by a combination of new processing steps, and by copolymerizing HEMA with a relatively hydrophobic monomer, hydroxypropyl methacrylate (HPMA). These advances produced systems with undetectable ciprofloxacin background release rates that are capable of US-facilitated drug release – up to 14-fold increases relative to controls both before and after US exposure. In addition, these observations are consistent with the hypothesis that US-mediated disorganization of the coating allows a transient flux of water into the matrix where its interaction with bound and dissolved drug facilitates its movement both within and out of the matrix.

The application of co-melt-extruded poly(ε-caprolactone) as a controlled release drug delivery device when combined with novel bioactive drug candidates: Membrane permeation and Hanson dissolution studies

Gardyne, Stephen J.; Mucalo, Michael R.; Rathbone, Michael J.
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
Publicado em 25/11/2011 EN
Relevância na Pesquisa
89.52059%
Eight bioactive drug compounds (abamectin, amoxicillin, dexamethasone, dexamethasone valerate, ketoprofen, melatonin, oestradiol 17β, and oestradiol benzoate) were combined via melt extrusion and disc pressing processes with a polycaprolactone (PCL) matrix and were then evaluated and compared via membrane diffusion and Hanson dissolution studies. This investigation was to determine the potential of this matrix to act as a controlled release drug delivery vehicle for a number of drugs not previously combined with PCL in a melt extrusion mix. The inclusion of the progesterone/PCL system, for which the drug release behaviour has been well studied before was intended for comparison with the PCL systems incorporating drugs that have received little research attention in the past. Initial studies centred on an evaluation of the permeation ability of the bioactive drugs dissolved in aqueous cyclodextrin solutions through a poly(ε-caprolactone) (PCL) membrane using Valia-Chien side-by-side cells. Permeation rates were mostly low and found to range from 0 to 122 μg h−1 with only ketoprofen, melatonin, and progesterone displaying rates exceeding 20 μg h−1. Hanson dissolution release profiles in aqueous alcohol were subsequently measured for the 9 melt extruded PCL/drug combinations and led to Hanson release rates of 0–556 μg cm−2 h−0.5 with dexamethasone...

Design and in vitro development of resorbable urologic drug delivery device

Tobias, Irene S. (Irene Sophie)
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 62 leaves
ENG
Relevância na Pesquisa
69.495347%
Implantable, controlled release drug delivery devices offer several advantages over systemic oral administration routes and immediate drug release treatments including direct therapy to target organ, more continuous maintenance of plasma and tissue drug levels and the potential for reduced side effects or toxicity. Urology has emerged as a unique field in which minimally invasive implantation techniques are available and such devices could provide improved beneficial therapies over conventional treatments. Urological indications for which localized drug therapy is already being advocated and investigated are highly suitable for treatment with implantable controlled release devices. This thesis describes the in vitro performance evaluation of an implantable, bio-resorbable device that can provide localized drug therapy of ciprofloxacin (CIP) to the seminal vesicle and nearby prostate gland for treatment of chronic prostatitis (CP). The device functions as an elementary osmotic pump (EOP) to release CIP for a period of 2-3 weeks after implantation in the seminal vesicle (SV) through transrectal needle injection or cystoscopic methods. The device is composed of an elastomeric, resorbable polymer cast in a tubular geometry with solid drug powder packed into its core and a micromachined release orifice drilled through its wall. Drug release experiments were performed to determine the effective release rate from a single orifice and the range of orifice size in which osmotic-controlled zero-order release was the dominant mechanism of drug delivery from the device. Device stability and function in an alkaline environment of similar pH to that of the SVs and infected prostate gland was also assessed in vitro. The device was found to function well in both de-ionized water and NaOH pH-8 solution with a sustained zero-order release rate of 2.47 ± 0.29 jtg/hr when fabricated with an orifice of diameter 100-150pm.; by Irene S. Tobias.; Thesis (M. Eng.)--Massachusetts Institute of Technology...

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
69.44992%
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...

The electrochemically engineered nanotubular titania surfaces for controlled and sustained delivery of drugs and drug carriers

Aw, M.; Gulati, K.; Ramakrishnan, S.; Addai-Mensah, J.; Losic, D.
Fonte: Engineers Australia; Australia Publicador: Engineers Australia; Australia
Tipo: Conference paper
Publicado em //2011 EN
Relevância na Pesquisa
69.31829%
Limitations of systemic therapy and poorly soluble drugs are persistent problems in pharmaceutical science. A promising alternative to improving drug efficacy and bioavailability is local therapy. Mesoporous structures such as Titania nanotube arrays (TNT) prepared by self-ordering electrochemical process have attracted considerable attention for the development of new implants for local delivery of therapeutics. In this work, we present a drug delivery system based on surface coating on TNT for controlled and extended delivery of poorly water-soluble drugs. TNT layers of highly ordered and vertically aligned nanotubes (20 μm long with diameters of 100 nm) were prepared by the anodization of titanium foil. Indomethacin, an anti-inflammatory drug, was used as an example of a poorly soluble (hydrophobic) drug. Polymeric micelle, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) loaded with indomethacin was used as the model of drug nanocarrier. Upon drug loading, TNT was coated with thin films of polymers prepared by different techniques: plasma polymerisation (poly-allylamine) and dip-coating (chitosan and poly (lactic-coglycolic) acid, PLGA). TNT implants before and after drug loading and polymer deposition were characterised by scanning electron microscopy (SEM)...

Drug delivery systems based on poly(e-caprolactone) for cancer treatment

S??ez-Fern??ndez, E.; Ruiz Mart??nez, Mar??a A.; Arias Mediano, Jos?? Luis
Fonte: Universidad de Granada, Facultad de Farmacia Publicador: Universidad de Granada, Facultad de Farmacia
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
78.61078%
Chemotherapy agents have little or no specificity over cancer cells, resulting in low therapeutic concentrations at the tumor site (a consequence of a broad systemic distribution), and severe side effects. With the aim of avoiding cancer therapy failure, several approaches such as design of new anticancer drugs, chemical engineering of conventional drugs and development of drug delivery systems have been proposed. The objective is to enhance drug localization at the tumor region (by controlling its biodistribution profile) and, therefore, to increase the anti-tumor efficacy (even in multi-drug resistant tumors), while reducing systemic side effects. One of the most promising approaches to the problem is the development of drug nanocarriers based on the polymer poly(e-caprolactone). In this review we will focus our attention on these polymeric colloids, particularly on the most significant characteristics and formulation procedures, and on their use as nanoplatforms for the delivery of chemotherapy agents to the tumor site. Furthermore, the most recent in vitro and in vivo investigations on the subject are extensively reviewed.

Bio-mimetic drug delivery systems designed to help the senior population reconstruct melatonin plasma profiles similar to those of the healthy younger population

Li, Ying; Wang, Liuyi; Wu, Li; Zhang, Xueju; Li, Xue; Guo, Zhen; Li, Haiyan; York, Peter; Gui, Shuangying; Zhang, Jiwen
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
69.493013%
The secretion of melatonin (MT) is obviously different in the younger and the senior sectors of the population, and the maximum plasma concentration of seniors is only half of that in the younger population group. If exogenous MT can be supplied to senior citizens based on the secretion rate and amount of endogenous MT in the younger population by a bio-mimetic drug delivery system (DDS), an improved therapeutic effect and reduced side effects can be expected. Based upon this hypothesis, the pharmacokinetic parameters of MT, namely, the absorption rate constant (ka), the elimination rate constant (ke), and the ratio of absorption rate (F) to the apparent volume of distribution (V) were obtained by a residual method depending on the plasma concentration curve of immediate release preparations in the healthy younger population. The dose-division method was applied to calculate the cumulative release profiles of MT achieved by oral administration of a controlled release drug delivery system (DDS) to generate plasma MT profiles similar to the physiological level-time profiles. The in vivo release of MT deduced from the healthy younger population physiological MT profiles as the pharmacokinetic output of the bio-mimetic DDS showed a two-phase profile with two different zero order release rates...

Developing a Dissociative Nanocontainer for Peptide Drug Delivery

Kelly, Patrick; Anand, Prachi; Uvaydov, Alexander; Chakravartula, Srinivas; Sherpa, Chhime; Pires, Elena; O’Neil, Alison; Douglas, Trevor; Holford, Mandë
Fonte: MDPI Publicador: MDPI
Tipo: Artigo de Revista Científica
EN_US
Relevância na Pesquisa
69.21251%
The potency, selectivity, and decreased side effects of bioactive peptides have propelled these agents to the forefront of pharmacological research. Peptides are especially promising for the treatment of neurological disorders and pain. However, delivery of peptide therapeutics often requires invasive techniques, which is a major obstacle to their widespread application. We have developed a tailored peptide drug delivery system in which the viral capsid of P22 bacteriophage is modified to serve as a tunable nanocontainer for the packaging and controlled release of bioactive peptides. Recent efforts have demonstrated that P22 nanocontainers can effectively encapsulate analgesic peptides and translocate them across blood-brain-barrier (BBB) models. However, release of encapsulated peptides at their target site remains a challenge. Here a Ring Opening Metathesis Polymerization (ROMP) reaction is applied to trigger P22 nanocontainer disassembly under physiological conditions. Specifically, the ROMP substrate norbornene (5-Norbornene-2-carboxylic acid) is conjugated to the exterior of a loaded P22 nanocontainer and Grubbs II Catalyst is used to trigger the polymerization reaction leading to nanocontainer disassembly. Our results demonstrate initial attempts to characterize the ROMP-triggered release of cargo peptides from P22 nanocontainers. This work provides proof-of-concept for the construction of a triggerable peptide drug delivery system using viral nanocontainers.

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
69.66683%

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...

Thermally Responsive Hydrogel-Nanoparticle Composite Materials for Therapeutic Delivery

Strong, Laura Elizabeth
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação
Publicado em //2014
Relevância na Pesquisa
69.5504%

Cancer is currently the second leading cause of death in the United States. Although many treatment options exist, some of the most common, including radiotherapy and chemotherapy, are restricted by dose-limiting toxicities. In addition, the largest hurdle for translating novel biological therapies such as siRNA into the clinic is lack of an efficient delivery mechanism to get the therapeutic into malignant cells. This work aims to improve this situation by engineering a minimally invasive controlled release system that specifically delivers therapeutics to the site of malignant tissue. This platform consists of two novel material components: a thermally responsive poly[N-isopropylacrylamide-co-acrylamide] (NIPAAm-co-AAm) hydrogel and gold-silica nanoshells. Therapeutic molecules are encapsulated within a poly(NIPAAm-co-AAm) hydrogel carrier, leading to increased serum stability, circulation time, and decreased exposure to off-site tissues. Additionally, gold-silica nanoshells embedded within this hydrogel will be used to optically trigger therapeutic release from the carrier. This hydrogel-nanoshell composite material was designed to be swollen under physiologic conditions (37 oC), and expel large amounts of water and absorbed molecules at higher temperatures (40-45 oC). This phase transition can be optically triggered by embedded gold-silica nanoshells...