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1.
J Int Soc Sports Nutr ; 18(1): 60, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503541

RESUMO

BACKGROUND: Numerous studies have demonstrated the efficacy of creatine supplementation for improvements in exercise performance. Few studies, however, have examined the effects of phosphocreatine supplementation on exercise performance. Furthermore, while polyphenols have antioxidant and anti-inflammatory properties, little is known regarding the influence of polyphenol supplementation on muscular strength, power, and endurance. Thus, the purpose of the present study was to compare the effects of 28 days of supplementation with phosphocreatine disodium salts plus blueberry extract (PCDSB), creatine monohydrate (CM), and placebo on measures of muscular strength, power, and endurance. METHODS: Thirty-three men were randomly assigned to consume either PCDSB, CM, or placebo for 28 days. Peak torque (PT), average power (AP), and percent decline for peak torque (PT%) and average power (AP%) were assessed from a fatigue test consisting of 50 maximal, unilateral, isokinetic leg extensions at 180°·s- 1 before and after the 28 days of supplementation. Individual responses were assessed to examine the proportion of subjects that exceeded a minimal important difference (MID). RESULTS: The results demonstrated significant (p < 0.05) improvements in PT for the PCDSB and CM groups from pre- (99.90 ± 22.47 N·m and 99.95 ± 22.50 N·m, respectively) to post-supplementation (119.22 ± 29.87 N·m and 111.97 ± 24.50 N·m, respectively), but no significant (p = 0.112) change for the placebo group. The PCDSB and CM groups also exhibited significant improvements in AP from pre- (140.18 ± 32.08 W and 143.42 ± 33.84 W, respectively) to post-supplementation (170.12 ± 42.68 W and 159.78 ± 31.20 W, respectively), but no significant (p = 0.279) change for the placebo group. A significantly (p < 0.05) greater proportion of subjects in the PCDSB group exceeded the MID for PT compared to the placebo group, but there were no significant (p > 0.05) differences in the proportion of subjects exceeding the MID between the CM and placebo groups or between the CM and PCDSB groups. CONCLUSIONS: These findings indicated that for the group mean responses, 28 days of supplementation with both PCDSB and CM resulted in increases in PT and AP. The PCDSB, however, may have an advantage over CM when compared to the placebo group for the proportion of individuals that respond favorably to supplementation with meaningful increases in muscular strength.


Assuntos
Força Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Fosfocreatina/farmacologia , Resistência Física/efeitos dos fármacos , Extratos Vegetais/farmacologia , Mirtilos Azuis (Planta)/química , Creatina , Suplementos Nutricionais , Método Duplo-Cego , Humanos , Masculino , Torque , Adulto Jovem
2.
Int J Pharm ; 608: 121127, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34560210

RESUMO

In vitro diffusion testing of topical formulations has long been examined using Franz diffusion chambers, however, Franz chambers are typically used with relatively large volumes, lack the air/membrane interface present in vivo, and do not account for changes in formula characteristics as solvent evaporates. Here we present our patented Munt-Dash diffusion chamber designed for direct spray application onto a model membrane. Diffusion characteristics from topical spray formulations utilizing both the Munt-Dash chamber and Franz diffusion chambers were evaluated and compared. Using diclofenac sodium and lidocaine hydrochloride as model drugs and shed snakeskin as a model for stratum corneum, test solutions were applied to Franz diffusion chambers using a pipette and to the Munt-Dash chamber using a high-speed syringe pump and sprayer. Both chambers presented permeability data consistent with previously reported in vitro and in vivo studies. Significant differences were observed in permeability by formulation and temperature. This suggests that although Franz chambers produce relevant data, the failure to account for small volumes and drying during application may produce misleading results. The Munt-Dash chamber may improve in vitro testing by providing these factors. This data suggests the Munt-Dash chamber is a suitable alternative to the Franz chamber for topical spray formulations.


Assuntos
Epiderme , Pele , Difusão , Cultura em Câmaras de Difusão , Técnicas In Vitro , Permeabilidade
3.
Ther Deliv ; 12(2): 145-158, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33583219

RESUMO

The topical and transdermal routes of drug administration are long known to the field of pharmaceutics. These routes have been explored for the delivery of a wide range of therapeutic agents over centuries. However, the anatomy of the skin and the physicochemical properties of molecules limit their transport via these routes. To overcome these challenges, a nano-phospholipid carrier called liposome was developed in the 1960s. Liposomal delivery of drugs was reported to be limited to the upper layers of skin. This led to the development of self-regulating and self-adaptable vesicles known as transfersomes. This review critically evaluates the barriers in delivery across the skin, recent advancements in liposomes, transfersomes and their impact in the pharmaceutical field.


Assuntos
Lipossomos , Absorção Cutânea , Administração Cutânea , Sistemas de Liberação de Medicamentos , Lipossomos/metabolismo , Fosfolipídeos , Pele/metabolismo
4.
J Drug Target ; 28(6): 655-667, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31886709

RESUMO

This study reports the development of a binary drug delivery system consisting of charged liposomes and an oppositely charged peptide-photosensitiser conjugate. Liposomes were prepared with phosphatidyl-l-serine as a negatively charged lipid. Calcein, a fluorophore marker, and doxorubicin, an anticancer drug, were used as model hydrophilic loads. The conjugate consisted of a positively charged arginine-rich peptide synthesised by solid-phase peptide synthesis, and a phthalocyanine derivative with characteristic absorption around 685 nm. Illumination of the binary system with far-red light of 12-15 mW/cm2 intensity resulted in 5- to 15-fold increase in release of payloads from the liposomes. The mechanism of drug release was based on photosensitised oxidation of lipids destabilising the liposomal membrane. The cytotoxicity of the liposomes loaded with doxorubicin was tested on B16-F10 melanoma and Y79 retinoblastoma cells. The cytotoxicity of the illuminated binary system in melanoma cell line was significantly higher as compared to the system without illumination. The components of the binary system can be individually prepared and stored with greater storage stability. However, their combination will allow for substantial release of hydrophilic payload from the liposomes under externally applied light.

5.
AAPS PharmSciTech ; 20(4): 160, 2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30968269

RESUMO

Over the last several decades, nanoparticulate delivery systems have emerged as advanced drug and gene delivery tools for cancer therapy. However, their translation into clinical use still poses major challenges. Even though many innovative nanoparticulate approaches have shown very positive results both in vitro and in vivo, few of them have found a place in clinical practice. Possible factors responsible for the existing gap in the translation of nanomedicine to clinical practice may include oversimplification of enhanced permeability and retention effect, lack of correlation between the in vivo animal data vs their translation in human, and challenging multiple biological steps experienced during systemic delivery of nanomedicine. Understanding these challenges and coming up with solutions to overcome them is an important step in effective translation of nanomedicine into clinical practice. This review focuses on advancements in the field of nanomedicine used for anti-cancer therapy, including passive targeting, active targeting, and stimuli-controlled delivery. The review further reveals some of the challenges that are currently faced by pharmaceutical scientists in translation of nanomedicine; these include lack of adequate models for preclinical testing that can predict efficacy in humans, absence of appropriate regulatory guidelines for their approval processes, and difficulty in scale-up of the manufacturing of nanodrug delivery systems. A better understanding of these challenges will help us in filling the gap between the bench and bedside in cancer therapy.


Assuntos
Sistemas de Liberação de Medicamentos , Técnicas de Transferência de Genes , Nanomedicina , Neoplasias/terapia , Animais , Humanos , Nanomedicina/métodos
6.
J Drug Target ; 27(9): 971-983, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30663420

RESUMO

Light-induced drug release has been explored as a strategy for externally modulating the release of drug from delivery systems. This study reports the development of a solid lipid nanoparticulate system (SLN) for paclitaxel (PTX), where photosensitizer-mediated oxidation of lipids was used as a mechanism for controlling the drug release. Low-intensity (23 mW/cm2) near-infrared (around 730 nm) illumination was externally applied as the light source. PTX release was less than 10% within 4 h from these SLN and was 8-fold higher after application of light at time zero. The other advantages of this approach include the use of ascorbic acid (ASC) as an antioxidant for enhancing the release and storage stability of the delivery system. Antioxidant like ASC in the SLN decrease the degradation of lipid by 8-fold within 4 months of storage. Presence of ASC and light illumination of SLN containing PTX further decreased the IC50 by 2 times in A549 cells. The uniqueness of this approach allows the possibility of external modulation to achieve pulsatile release from the delivery system. The light used in the NIR spectral range of 700-850 nm, which has the greatest tissue penetration ability, with a low intensity will be safe for normal tissues.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Lipídeos/química , Nanopartículas , Paclitaxel/administração & dosagem , Células A549 , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Ácido Ascórbico/química , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Humanos , Concentração Inibidora 50 , Luz , Paclitaxel/farmacologia , Fatores de Tempo
7.
Ther Deliv ; 9(12): 857-872, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30444455

RESUMO

The poor pharmacokinetic parameters and low solubility of many anticancer therapeutics have warranted the use of drug-delivery systems such as liposomes. Overcoming some drawbacks of the conventional liposomes, targeted liposomal delivery by longer circulation time by addition of poly(ethylene glycol) to the liposomal surface and further adding specific ligands to achieve ligand selective retention and uptake has been introduced. PEGylated liposomes are the only second-generation liposomal formulations in clinical use and are now being challenged with the allergenic response they pose even in the treatment of naive patients. This article will review the challenges and hindrances in the use of long circulating liposomes and explore the opportunities to overcome this issue.


Assuntos
Antineoplásicos/administração & dosagem , Composição de Medicamentos/métodos , Neoplasias/tratamento farmacológico , Polietilenoglicóis/química , Animais , Antineoplásicos/farmacocinética , Modelos Animais de Doenças , Composição de Medicamentos/tendências , Meia-Vida , Humanos , Lipossomos , Solubilidade , Fatores de Tempo
8.
AAPS PharmSciTech ; 19(6): 2543-2553, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29948986

RESUMO

The objective of this study was to develop a nanodelivery system containing a mucoadhesive polymer hyaluronic acid (HA) for oral delivery. Metformin was used as a model drug. Blank and drug-loaded HA nanostructures were prepared by precipitation method and characterized for particle size (PS), zeta potential (ZP), physical stability (over 65 days), surface morphology, moisture content, and physical state of the drug in the nanostructures. The cytotoxicity and hemolysis potential of the delivery system was assessed in Caco-2 cells and whole human blood, respectively. The in vitro release of metformin and its uptake in Caco-2 cells was evaluated using high-performance liquid chromatography. Ex vivo permeability of metformin was measured through goat intestinal membrane. The nanoparticles were physically stable and neutrally charged with an average PS of 114.53 ± 12.01 nm. This nanodelivery system existed as nanofibers containing metformin in a crystalline state. This delivery system released the drug rapidly with > 50% of metformin released within 1 h. Cellular uptake studies on Caco-2 cells indicated higher uptake of metformin from nanoparticle as compared to metformin in solution, up to first 45 min. Ex vivo permeability studies on the other hand showed a higher metformin permeability from solution relative to that from nanoparticles through the goat intestinal membrane. Metformin nanoparticles were non-toxic at therapeutic concentrations in Caco-2 cells and showed no hemolytic effect to RBCs. This study indicates the preparation, characterization, as well as the potential use of HA nanostructures for oral delivery.


Assuntos
Sistemas de Liberação de Medicamentos , Ácido Hialurônico/administração & dosagem , Metformina/administração & dosagem , Administração Oral , Animais , Células CACO-2 , Sistemas de Liberação de Medicamentos/métodos , Humanos , Ácido Hialurônico/química , Metformina/química , Metformina/farmacocinética , Nanoestruturas/administração & dosagem , Permeabilidade
9.
AAPS PharmSciTech ; 18(7): 2814-2823, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28397161

RESUMO

Curcumin and resveratrol are naturally occurring polyphenolic compounds having anti-cancer potential. However, their poor aqueous solubility and bioavailability limit their clinical use. Entrapment of hydrophobic drugs into hydrophilic nanoparticles such as calcium alginate presents a means to deliver these drugs to their target site. Curcumin and resveratrol-loaded calcium alginate nanoparticles were prepared by emulsification and cross-linking process. The nanoparticles were characterized for particle size, zeta potential, moisture content, physical state of the drugs, physical stability, and entrapment efficiency. An UPLC method was developed and validated for the simultaneous analysis of curcumin and resveratrol. Alginate nanoformulation was tested for in vitro efficacy on DU145 prostate cancer cells. The particle size of the nanosuspension and freeze-dried nanoparticles was found to be 12.53 ± 1.06 and 60.23 ± 15 nm, respectively. Both DSC and powder XRD studies indicated that curcumin as well as resveratrol were present in a non-crystalline state, in the nanoparticles. The entrapment efficiency for curcumin and resveratrol was found to be 49.3 ± 4.3 and 70.99 ± 6.1%, respectively. Resveratrol showed a higher percentage of release than curcumin (87.6 ± 7.9 versus 16.3 ± 3.1%) in 24 h. Curcumin was found to be taken up by the cells from solution as well as the nanoparticles. Resveratrol had a poor cellular uptake. The drug-loaded nanoparticles exhibit cytotoxic effects on DU145 cells. At high concentration, drug solution exhibited greater toxicity than nanoparticles. The alginate nanoformulation was found to be safe for intravenous administration.


Assuntos
Alginatos/química , Antineoplásicos/administração & dosagem , Curcumina/administração & dosagem , Nanopartículas/química , Neoplasias da Próstata/tratamento farmacológico , Estilbenos/administração & dosagem , Linhagem Celular Tumoral , Curcumina/química , Curcumina/farmacologia , Liberação Controlada de Fármacos , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Humanos , Masculino , Tamanho da Partícula , Neoplasias da Próstata/patologia , Resveratrol , Estilbenos/química , Estilbenos/farmacologia
10.
AAPS PharmSciTech ; 16(6): 1425-33, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25986597

RESUMO

Unprotected sunlight exposure is a risk factor for a variety of cutaneous cancers. Topically used dihydroxyacetone (DHA) creates, via Maillard reaction, chemically fixed keratin sunscreen in the stratum corneum with significant protection against UVA/Soret radiation. When used in conjunction with naphthoquinones a naphthoquinone-modified DHA Maillard reaction is produced that provides protection across the UVB/UVA/Soret spectra lasting up to 1 week, resisting sweating and contact removal. The aim of this study was to examine a simplified version of this formulation for effect on UV transmission and to determine if penetration levels merit toxicity concerns. Permeability was demonstrated for freshly prepared DHA (30 mg/mL) and lawsone (0.035 mg/mL) alone and in combination using a side-by-side diffusion apparatus at 37°C over 48 h across shed snake skin and dermatomed pig skin. These samples were then examined for effectiveness and safety. Concentrations were determined by HPLC and UPLC monitored from 250-500 nm. Lawsone flux significantly decreased across pig skin (20.8 (± 4.8) and 0.09 (± 0.1) mg/cm(2) h without and with DHA, respectively) but did not change across shed snake skin in the presence of DHA. Significantly reduced lawsone concentration was noted in donor chambers of combined solutions. Damage was not observed in any skins. Darker coloration with greater UV absorbance was observed in skins exposed to the combined solution versus individual solutions. This study confirmed that combined DHA and lawsone provided effective blocking of ultraviolet light through products bound in keratinized tissue. DHA permeation levels in pig skin suggest further in vitro and in vivo study is required to determine the safety of this system.


Assuntos
Di-Hidroxiacetona/administração & dosagem , Naftoquinonas/administração & dosagem , Pele/efeitos dos fármacos , Protetores Solares/administração & dosagem , Animais , Boidae/metabolismo , Difusão , Suínos , Raios Ultravioleta
11.
Ther Deliv ; 6(1): 27-39, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25565439

RESUMO

AIM: Poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing both paclitaxel (PTX) and gemcitabine hydrochloride (GEM) were prepared and the effect of lyophilization and spray drying on physicochemical characteristics of these nanoparticles were evaluated. METHODS: Nanoemulsions were prepared by oil-in-water emulsion solvent diffusion technique using sonication and high-pressure homogenization. Nanoemulsion was dried using lyophilization or spray drying and drug content analyzed by high-performance liquid chromatography (HPLC). RESULTS: The particle size of the nanoemulsion was 183.6 ± 10.8 nm and the entrapment efficiency for PTX and GEM was 72.01 ± 1.35% and 6.95 ± 3.97%. Many properties including particle size, stability, surface morphology, moisture content, release characteristic and cellular uptake in MDCK and MDA-MB-231 cells were affected by the method of drying. CONCLUSION: The lyophilized nanoparticles were smaller in size with higher stability and cellular uptake than spray-dried nanoparticles.


Assuntos
Antineoplásicos/administração & dosagem , Ácido Láctico/química , Nanopartículas/química , Ácido Poliglicólico/química , Antineoplásicos/química , Antineoplásicos/farmacocinética , Varredura Diferencial de Calorimetria , Sistemas de Liberação de Medicamentos , Estabilidade de Medicamentos , Liofilização , Interações Hidrofóbicas e Hidrofílicas , Microscopia de Força Atômica , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Solubilidade
12.
AAPS PharmSciTech ; 16(1): 98-107, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25190362

RESUMO

The relapse of cancer after first line therapy with anticancer agents is a common occurrence. This recurrence is believed to be due to the presence of a subpopulation of cells called cancer stem cells in the tumor. Therefore, a combination therapy which is susceptible to both types of cells is desirable. Delivery of this combinatorial approach in a nanoparticulate system will provide even a better therapeutic outcome in tumor targeting. The objective of this study was to develop and characterize nanoparticulate system containing two anticancer agents (cyclopamine and paclitaxel) having different susceptibilities toward cancer cells. Both drugs were entrapped in glyceryl monooleate (GMO)-chitosan solid lipid as well as poly(glycolic-lactic) acid (PLGA) nanoparticles. The cytotoxicity studies were performed on DU145, DU145 TXR, and Wi26 A4 cells. The particle size of drug-loaded GMO-chitosan nanoparticles was 278.4 ± 16.4 nm with a positive zeta potential. However, the PLGA particles were 234.5 ± 6.8 nm in size with a negative zeta potential. Thermal analyses of both nanoparticles revealed that the drugs were present in noncrystalline state in the matrix. A sustained in vitro release was observed for both the drugs in these nanoparticles. PLGA blank particles showed no cytotoxicity in all the cell lines tested, whereas GMO-chitosan blank particles showed substantial cytotoxicity. The types of polymer used for the preparation of nanoparticles played a major role and affected the in vitro release, cytotoxicity, and uptake of nanoparticles in the all the cell lines tested.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/síntese química , Nanocápsulas/química , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Difusão , Composição de Medicamentos/métodos , Estabilidade de Medicamentos , Humanos , Masculino , Nanocápsulas/administração & dosagem , Nanocápsulas/ultraestrutura , Células-Tronco Neoplásicas/patologia , Paclitaxel/administração & dosagem , Paclitaxel/química , Tamanho da Partícula , Neoplasias da Próstata/patologia , Resultado do Tratamento , Alcaloides de Veratrum/administração & dosagem , Alcaloides de Veratrum/química
13.
Nanomedicine (Lond) ; 7(12): 1863-76, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22709346

RESUMO

AIM: The objective of this study was to investigate the influence of the high-pressure homogenization (HPH) process and stabilizers on the physicochemical properties of glycerol monooleate (GMO)/chitosan nanostructures using curcumin as a model hydrophobic drug. MATERIALS & METHODS: The oil-in-water nanoemulsion of the GMO/chitosan system was prepared by sonication and HPH techniques using two different stabilizers (polyvinyl alcohol [PVA] and poloxamer 407). The particle size (PS), ζ-potential (ZP) and physical stability of the nanoemulsion were investigated. These nanoemulsions were lyophilized and characterized for PS, ZP, surface morphology, moisture content and physical form of the drug in the nanostructures. The in vitro release and the uptake of curcumin in Caco-2 cells were evaluated using an ultra-performance liquid chromatography method. RESULTS: Three cycles of HPH produced a 50-65% reduction in the PS of the nanoemulsion. A change in stabilizer, from PVA to poloxamer, did not affect the PS, physical stability, moisture content or the physical form of the drug in the formulation. However, there was a significant change in the ZP, surface morphology, in vitro release rate and cellular uptake from the two formulations. CONCLUSION: The process of HPH effectively reduces the PS of the GMO/chitosan nanoemulsions loaded with the hydrophobic drug. The type of stabilizer used affects several physicochemical properties of the GMO/chitosan nanostructures. Compared with PVA, poloxamer 407 is a more effective stabilizer for stabilizing the GMO/chitosan system containing a hydrophobic drug nanoemulsion at low concentrations.


Assuntos
Antineoplásicos/administração & dosagem , Quitosana/química , Curcumina/administração & dosagem , Portadores de Fármacos/química , Excipientes/química , Glicerídeos/química , Nanoestruturas/química , Antineoplásicos/farmacocinética , Células CACO-2 , Curcumina/farmacocinética , Humanos , Poloxâmero/química , Álcool de Polivinil/química , Pressão
14.
Nanomedicine (Lond) ; 6(8): 1397-412, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22091968

RESUMO

AIMS: The present research focuses on the development of the surface modified solid lipid nanoparticulate (SLN) system for enhancing the stability and sustaining the release of a model hydrophilic drug ifosfamide. MATERIALS & METHODS: SLNs consisting of glyceryl monooleate (GMO) and chitosan were prepared by double emulsion technique, crosslinked with sodium tripolyphosphate, followed by lyophilization under two different vacuum conditions. The physicochemical characterization of SLNs included evaluation of surface morphology, particle size and surface charge, moisture content and physical state of the drug in the delivery system. The in vitro drug release and the stability were evaluated using high-performance liquid chromatography and liquid chromatography/mass spectrometry, respectively. Cellular permeability and subcellular localization studies were performed using Caco-2 cells. RESULTS: Different chamber pressures during lyophilization produced SLNs with different morphologies and moisture contents. SLNs demonstrated high encapsulation efficiency, sustained release, and enhanced stability of ifosfamide with a high cellular uptake and permeability for Caco-2 cells. CONCLUSION: GMO and chitosan SLNs could be successfully used for enhancing the stability, sustaining the release, enhancing the targeting and permeability characteristics of ifosfamide.


Assuntos
Ifosfamida/química , Lipídeos/química , Nanopartículas/química , Células CACO-2 , Varredura Diferencial de Calorimetria , Química Farmacêutica , Quitosana/química , Cromatografia Líquida de Alta Pressão , Glicerídeos/química , Humanos , Ifosfamida/farmacocinética , Microscopia Eletrônica de Varredura , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria
15.
Nanomedicine (Lond) ; 6(3): 437-48, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21542683

RESUMO

AIMS: This investigation compared the tumor distribution, efficacy, blood pharmacokinetic parameters and hematological alterations following treatment with chitosan/glyceryl-monooleate (GMO) nanostructures containing paclitaxel (PTX) to a conventional formulation of PTX (Taxol(®)) in BALB/c female mice. MATERIALS & METHODS: The tumor and blood concentrations of PTX were evaluated by HPLC and the pharmacokinetic parameters were determined through noncompartmental methods. Tumor development was evaluated by histopathological methods and hematological composition was monitored through differential white blood cells counts. RESULTS: Lower localized or intravenous doses of PTX-chitosan/GMO nanostructures significantly increased the antitumor activity of paclitaxel. The tumor distribution studies showed effective concentrations in the tumors with the chitosan/GMO formulation while systemic blood levels remained lower than after administration of the conventional formulation. CONCLUSION: Delivery systems consisting of chitosan/GMO and PTX are safe and effective administered locally (intratumorally) or intravenously.


Assuntos
Antineoplásicos Fitogênicos/farmacocinética , Quitosana/farmacocinética , Glicerídeos/farmacocinética , Nanoestruturas/administração & dosagem , Neoplasias/tratamento farmacológico , Paclitaxel/farmacocinética , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Quitosana/administração & dosagem , Sistemas de Liberação de Medicamentos , Feminino , Glicerídeos/administração & dosagem , Contagem de Leucócitos , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/metabolismo , Paclitaxel/administração & dosagem
16.
AAPS PharmSciTech ; 11(1): 392-401, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20238190

RESUMO

The objectives of this study are to enhance cellular accumulation of gemcitabine with chitosan/glyceryl monooleate (GMO) nanostructures, and to provide significant increase in cell death of human pancreatic cancer cells in vitro. The delivery system was prepared by a multiple emulsion solvent evaporation method. The nanostructure topography, size, and surface charge were determined by atomic force microscopy (AFM), and a zetameter. The cellular accumulation, cellular internalization and cytotoxicity of the nanostructures were evaluated by HPLC, confocal microscopy, or MTT assay in Mia PaCa-2 and BxPC-3 cells. The average particle diameter for 2% and 4% (w/w) drug loaded delivery system were 382.3 +/- 28.6 nm, and 385.2 +/- 16.1 nm, respectively with a surface charge of +21.94 +/- 4.37 and +21.23 +/- 1.46 mV. The MTT cytotoxicity dose-response studies revealed the placebo at/or below 1 mg/ml has no effect on MIA PaCa-2 or BxPC-3 cells. The delivery system demonstrated a significant decrease in the IC50 (3 to 4 log unit shift) in cell survival for gemcitabine nanostructures at 72 and 96 h post-treatment when compared with a solution of gemcitabine alone. The nanostructure reported here can be resuspended in an aqueous medium that demonstrate increased effective treatment compared with gemcitabine treatment alone in an in vitro model of human pancreatic cancer. The drug delivery system demonstrates capability to entrap both hydrophilic and hydrophobic compounds to potentially provide an effective treatment option in human pancreatic cancer.


Assuntos
Quitosana/uso terapêutico , Nanoestruturas , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/terapia , Sobrevivência Celular/efeitos dos fármacos , Desoxicitidina/análogos & derivados , Emulsões/farmacologia , Emulsões/uso terapêutico , Glicerídeos , Humanos , Concentração Inibidora 50 , Pâncreas/efeitos dos fármacos
17.
Crit Rev Ther Drug Carrier Syst ; 26(4): 333-72, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20001890

RESUMO

Paclitaxel (PTX) is a potent anticancer agent whose clinical usefulness is marred by a delivery problem that is caused by its unfavorable pharmacokinetic and physical properties. Paclitaxel is currently formulated in a mixture of Cremophor EL and ethanol, which is diluted 5-20 times with normal saline or 5% dextrose prior to administration via slow infusion to avoid precipitation in plasma. Many adverse reactions to the PTX formulation have been reported because of the presence of Cremophor EL, including hypersensitivity reactions, nephrotoxicity, and neurotoxicity. Cremophor EL also causes vasodilation, labored breathing, lethargy, hypotension, and leaching of plasticizers, such as diethylhexylpthalate, from the polyvinylchloride infusion bags/sets. Significant research efforts have been conducted to develop an alternative formulation approach to increase the aqueous solubility of PTX without using Cremophor, thereby decreasing its toxicity. This article reviews the various investigated formulation approaches including pastes; liposomes; conjugates with antibodies, peptides, and fatty acids; nanospheres and microspheres; cyclodextrin complexes; emulsions; mucoadhesive gel; prodrugs; and nanoparticulate systems. The pros and cons of each approach are also discussed. Finally, this review concludes with a discussion of nanoparticulate delivery, which is the most promising PTX delivery system of the future because it incorporates the benefits of other approaches such as conjugation, complexation, and prodrugs.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias/tratamento farmacológico , Paclitaxel/uso terapêutico , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Química Farmacêutica/métodos , Química Farmacêutica/tendências , Sistemas de Liberação de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/tendências , Humanos , Paclitaxel/química , Paclitaxel/farmacocinética , Excipientes Farmacêuticos/efeitos adversos , Excipientes Farmacêuticos/química
18.
19.
Artigo em Inglês | MEDLINE | ID: mdl-22469177
20.
J Pharm Biomed Anal ; 43(5): 1796-803, 2007 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-17184951

RESUMO

ON 01210.Na is a chlorobenzylsulfone derivative with potential property to mitigate the effects of accidental or intentional exposure to life threatening levels of radiation. A simple and sensitive HPLC method was developed and validated for the assay of ON 01210.Na. The isocratic system used a mobile phase consisting of acetonitrile:0.1% trifluroacetic acid in water (60:40, v/v) at a flow rate of 1 ml/min. The method used a C-18 Gemini column (250 mm x 4.6 mm) with column effluents monitored at 254 nm. Forced degradation of the drug was achieved by autoclaving ON 01210.Na with 0.05 N HCl, 0.05 N NaOH or 1.5% (v/v) hydrogen peroxide. The assay validation parameters evaluated include specificity, linearity, precision, accuracy and sensitivity. The retention time of the drug and the other effluents were well within 7 min. Standard curves were linear over the concentration range of 10-500 microg/ml. The R.S.D. values for the within-day and day-to-day precision ranged from 0.4 to 2.5 and 2.2 to 4.4%, respectively. The R.S.D. for accuracy measurement ranged from 0.85 to 1.7%. The critical level, the detection level and the determination level for this assay were 2.86+/-0.67, 5.69+/-0.67 and 15.6+/-1.8 microg/ml, respectively. A simple, sensitive and stability indicating HPLC assay was developed and validated for the analysis of a novel radioprotectant. This method was used to evaluate the aqueous as well as solid-state stability of this drug during autoclaving.


Assuntos
Cromatografia Líquida/métodos , Mesilatos/química , Protetores contra Radiação/análise , Sulfonamidas/análise , Acetonitrilas/química , Cromatografia Líquida/instrumentação , Estabilidade de Medicamentos , Ácido Clorídrico/farmacologia , Protetores contra Radiação/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Hidróxido de Sódio/farmacologia , Sulfonamidas/química , Ácido Trifluoracético/química , Água/química
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