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1.
Biol Trace Elem Res ; 199(7): 2621-2626, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32865723

RESUMO

Excess fluoride intake has been linked with various pathological conditions. The objective of the present study was to understand the role of fluoride in neurotoxic, neuroinflammatory, and neurodegenerative changes in the brain tissue of Wistar rats. Wistar rats were fed with water containing 20-100 ppm (ppm) sodium fluoride (NaF). An array of neurotransmitters (acetylcholine, dopamine, epinephrine, norepinephrine, serotonin, histamine, and glutamate) expression levels were estimated with respect to different fluoride concentrations. Additionally, its effect on the expression levels of specific neuroinflammatory markers (iNOS, COX-2, TNF-α, PKC, VEGF, and HSP-70) in brain tissues of Wister rats was assessed. An increase in NaF concentration resulted in increased fluoride deposition in the brain which in turn caused increase levels of epinephrine, histamine, serotonin, and glutamate and decreased levels of norepinephrine, acetylcholine, and dopamine in a dose-dependent manner. Tissue fluoride levels of the hippocampus, neocortex, cerebellum, spinal cord, and sciatic nerve increased significantly in fluoride fed rats. Transmission electron microscopy in the experimental animals revealed axon deterioration, myelin sheath degeneration, and dark cells with scanty cytoplasm in the spinal cord and sciatic nerve. Additionally, vacuolated swollen mitochondria were observed in the neocortex, hippocampus, and cerebellum. Results suggest excess fluoride intake modulates a set of biological marker and promote neuroinflammatory and neurodegenerative condition in Wister rats. Therefore, we conclude that the accumulation of NaF alters the neurological function which leads to neurodegenerative disorders.


Assuntos
Fluoretos , Fluoreto de Sódio , Animais , Biomarcadores , Encéfalo , Fluoretos/toxicidade , Ratos , Ratos Wistar , Fluoreto de Sódio/toxicidade
3.
Int J Pharm ; 532(1): 90-104, 2017 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-28859938

RESUMO

This study was conducted to provide a mechanistic account for understanding the synthesis, characterization and solubility phenomena of vitamin complexes with cyclodextrins (CD) for enhanced solubility and stability employing experimental and in silico molecular modeling strategies. New geometric, molecular and energetic analyses were pursued to explicate experimentally derived cholecalciferol complexes. Various CD molecules (α-, ß-, γ-, and hydroxypropyl ß-) were complexed with three vitamins: cholecalciferol, ascorbic acid and α-tocopherol. The Inclusion Efficiency (IE%) was computed for each CD-vitamin complex. The highest IE% achieved for a cholecalciferol complex was for 'ßCDD3-8', after utilizing a unique CD:cholecalciferol molar synthesis ratio of 2.5:1, never before reported as successful. 2HPßCD-cholecalciferol, γCD-cholecalciferol and α-tocopherol inclusion complexes (IC's) reached maximal IE% with a CD:vitamin molar ratio of 5:1. The results demonstrate that IE%, thermal stability, concentration, carrier solubility, molecular mechanics and intended release profile are key factors to consider when synthesizing vitamin-CD complexes. Phase-solubility data provided insights into the design of formulations with IC's that may provide analogous oral vitamin release profiles even when hydrophobic and hydrophilic vitamins are co-incorporated. Static lattice atomistic simulations were able to validate experimentally derived cholecalciferol IE phenomena and are invaluable parameters when approaching formulation strategies using CD's for improved solubility and efficacy of vitamins.


Assuntos
Ácido Ascórbico/química , Colecalciferol/química , Ciclodextrinas/química , Vitaminas/química , alfa-Tocoferol/química , Varredura Diferencial de Calorimetria , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Solubilidade , Difração de Raios X
4.
AAPS PharmSciTech ; 18(7): 2479-2493, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28205143

RESUMO

A multifunctional platform to deliver three diverse proteins of insulin, interferon beta (INF-ß) and erythropoietin (EPO), using a novel copolymeric microparticulate system of TMC-PEGDMA-MAA, was synthesised as an intelligent pH-responsive 2-fold gastric and intestinal absorptive system. Physiochemical and physicomechanical studies proved the degree of crystallinity that supported the controlled protein delivery of the microparticulate system. The copolymer was tableted before undertaking in vitro and in vivo analysis. After 2.5 h in simulated gastric fluid (SGF), insulin showed a fractional release of 3.2% in comparison to simulated intestinal fluid (SIF), in which a maximum of 83% of insulin was released. Similarly, INF-ß and EPO released 3 and 9.7% in SGF and a maximum of 74 and 81.3% in SIF, respectively. In vivo studies demonstrated a significant decrease in blood glucose by 54.19% within 4 h post-dosing, and the comparator formulation provided 74.6% decrease in blood glucose within the same time period. INF-ß peak bioavailable dose in serum was calculated to be 1.3% in comparison to an SC formulation having a peak concentration of 0.9%, demonstrating steady-state release for 24 h. EPO-loaded copolymeric microparticles had a 1.6% peak bioavailable concentration, in comparison to the 6.34% peak concentration after 8 h from the SC comparator formulation.


Assuntos
Eritropoetina/administração & dosagem , Insulina/administração & dosagem , Interferon beta/administração & dosagem , Administração Oral , Animais , Disponibilidade Biológica , Glicemia/análise , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Absorção Gástrica , Concentração de Íons de Hidrogênio , Interferon beta/sangue , Metacrilatos/química , Polietilenoglicóis/química , Coelhos
5.
AAPS PharmSciTech ; 18(3): 654-670, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27184677

RESUMO

In this study, an optimized epichlorohydrin-crosslinked semi-interpenetrating polymer network xerogel matrix system (XePoMas) for the controlled delivery of sulpiride was prepared. The ability of XePoMas to sustain drug release was determined by in vitro and in vivo drug release experiments. Swelling of the xerogel over the 24-h experimental period ranged from 346 to 648%; swelling was observed to increase exponentially over the initial 8 h. In vitro drug release depicted a linear zero order drug release profile with an R 2 value of 0.9956. The ability of the fabricated XePoMas to sustain drug release and enhance bioavailability of sulpiride in vivo was investigated by evaluating the plasma drug concentration over 24 h in the large pig model. The optimized XePoMas formulation was shown to increase intestinal absorption of sulpiride to a greater extent than the marketed product in vivo, with a C max of 830.58 ng/mL after 15 h.


Assuntos
Polietilenoglicóis/química , Polímeros/química , Polissacarídeos Bacterianos/química , Sulpirida/química , Administração Oral , Animais , Disponibilidade Biológica , Química Farmacêutica/métodos , Preparações de Ação Retardada/química , Preparações de Ação Retardada/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Epicloroidrina/química , Epicloroidrina/metabolismo , Sulpirida/metabolismo , Suínos
6.
Pharm Dev Technol ; 21(7): 832-846, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26333524

RESUMO

Few researchers have investigated the use of multiple physiological enhancers combined with synthetic carriers to augment delivery of nutraceuticals. The current work describes the development of an oral delivery system termed a bioactive association platform (BAP) capable of delivering nutraceutical actives from a formulation framework specifically for enhancing the in vitro and in vivo performance of model vitamin, cholecalciferol (Vitamin D3). Synthesis of a novel triple vitamin minitablet and an optimized bile salt/lipase alginate-glycerin film provided unique oral components for inclusion in a BAP capsule. Component validation and physicochemical characterizations included comparative ex vivo permeability, chemical structure mapping, thermodynamic analysis and magnetic resonance imaging. In vitro dissolution studies of the BAP produced an area under the dissolution curve (AUC) for cholecalciferol release that was 28% greater than a conventional comparator product. A total of 84.01% of cholecalciferol was released from the BAP within 3 h versus only 59% from a comparator. Ex vivo permeation studies revealed superior cholecalciferol membrane diffusion from the triple vitamin minitablet BAP component. In vivo performance showed a greater mean change from baseline cholecalciferol to peak plasma levels (Cmax) from the BAP compared to the comparator (55.66 versus 46.05 ng/mL). Cholecalciferol bioavailability was improved in vivo with an AUC0-inf from the BAP that was 3.2× greater than the conventional product. The BAP was also superior at improving and maintaining serum levels of the main metabolite, 25-hydroxyvitamin D3, compared to the conventional system. In vitro and in vivo results thus confirmed improvements in cholecalciferol dissolution, membrane permeability and plasma drug levels. The study results position the BAP as an ideal oral vehicle for enhanced delivery of cholecalciferol.


Assuntos
Ácidos e Sais Biliares/química , Colecalciferol/administração & dosagem , Colecalciferol/química , Lipase/química , Polímeros/química , Comprimidos/administração & dosagem , Comprimidos/química , Administração Oral , Animais , Disponibilidade Biológica , Cápsulas/administração & dosagem , Cápsulas/química , Cápsulas/metabolismo , Química Farmacêutica/métodos , Colecalciferol/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Excipientes/química , Permeabilidade , Solubilidade , Suínos , Comprimidos/metabolismo , Vitamina D/análogos & derivados , Vitamina D/química , Vitaminas/administração & dosagem , Vitaminas/química
7.
Pharm Dev Technol ; 21(3): 354-66, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25560782

RESUMO

The drug treatment of acute disorders such as neuropathic pain, migraines, insomnia, vomiting, allergic rhinitis or erectile dysfunction requires an immediate pharmacological effect that may be achieved through parenteral drug administration. However, the parenteral route is not always convenient for reasons that are well known. Therefore, in the recent past there has been a barrage of interest in formulating new, non-invasive, reliable and convenient oradispersible drug delivery technologies (ODDTs). Research in this area has focused extensively on developing ODDTs that are capable of releasing drugs immediately when they come into contact with saliva. This disregards the necessity of water during administration and several other advantages that is an attribute that makes this technology lucrative for groups such as pediatrics, geriatrics, psychiatrics and unconscious patients. Many reviews have been compiled on the salient features of ODDTs. However, none to date has focused on the actual formulation techniques used to produce these technologies and how this may impact their disintegration and physical stability for fulfilling their purpose. Therefore this review provides a concise incursion on the recent formulation techniques, excipients used as well as methods of testing the performance of ODDTs and critically assesses these in terms of improving their performance.


Assuntos
Preparações Farmacêuticas/química , Química Farmacêutica , Sistemas de Liberação de Medicamentos/métodos , Excipientes/química , Humanos , Tecnologia Farmacêutica/métodos
8.
Biomed Res Int ; 2015: 484963, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26491671

RESUMO

The efficient noninvasive treatment of neurodegenerative disorders is often constrained by reduced permeation of therapeutic agents into the central nervous system (CNS). A vast majority of bioactive agents do not readily permeate into the brain tissue due to the existence of the blood-brain barrier (BBB) and the associated P-glycoprotein efflux transporter. The overexpression of the MDR1 P-glycoprotein has been related to the occurrence of multidrug resistance in CNS diseases. Various research outputs have focused on overcoming the P-glycoprotein drug efflux transporter, which mainly involve its inhibition or bypassing mechanisms. Studies into neurodegenerative disorders have shown that the P-glycoprotein efflux transporter plays a vital role in the progression of schizophrenia, with a noted increase in P-glycoprotein function among schizophrenic patients, thereby reducing therapeutic outcomes. In this review, we address the hypothesis that methods employed in overcoming P-glycoprotein in cancer and other disease states at the level of the BBB and intestine may be applied to schizophrenia drug delivery system design to improve clinical efficiency of drug therapies. In addition, the current review explores polymers and drug delivery systems capable of P-gp inhibition and modulation.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/efeitos dos fármacos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Antipsicóticos , Barreira Hematoencefálica/metabolismo , Resistência a Medicamentos , Esquizofrenia/metabolismo , Antipsicóticos/farmacocinética , Antipsicóticos/uso terapêutico , Humanos
9.
Int J Pharm ; 496(2): 863-77, 2015 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-26456249

RESUMO

This study reports the use of biocompatible and biodegradable polymers for the formulation and design of an implantable multipolymeric drug delivery device (MDDD) for the management of AIDS dementia complex (ADC), a debilitating condition affecting the cognitive, motor and behavioral systems in HIV+ individuals. A 3-factor Box-Behnken statistical design was employed for the optimization of nanoparticle and multipolymeric scaffold formulations. Fifteen formulations were generated using the Box-Behnken template, which were assessed for physicochemical and physicomechanical characterization. The optimised nanoparticle formulation yielded nanoparticles measuring 68.04nm in size and zeta potential (ZP) of -13.4mV was calculated for the colloidal system. In an attempt to further retard drug release and to formulate a device for implantation in the frontal lobe of the brain, nanoparticles were dispersed within a multipolymeric matrix. Matrix erosion was calculated at 28% for multipolymeric scaffold and a matrix resilience of 4.451% was observed 30 days post exposure to PBS, indicating slow degradation of the MDDD. In vivo studies showed 12.793ng/mL and 35.225ng/mL AZT level in plasma and CSF. In view of the physicomechanical properties, in vitro and in vivo drug release kinetics of MDDD makes it a potential candidate for the management of the ADC.


Assuntos
Complexo AIDS Demência/terapia , Alicerces Teciduais , Complexo AIDS Demência/patologia , Animais , Encéfalo/patologia , Química Farmacêutica , Sistemas de Liberação de Medicamentos/instrumentação , Humanos , Masculino , Microscopia Eletrônica de Varredura , Nanopartículas/química , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Zidovudina/farmacocinética , Zidovudina/uso terapêutico
10.
S Afr Med J ; 105(8): 656-8, 2015 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-26449698

RESUMO

BACKGROUND: Before the 1930s, squamous cell carcinoma (SCC) of the oesophagus was almost unknown among black South Africans. From the 1930s the annual frequency rose. A dietary cause was sought, the staple diet of black people having changed from sorghum to maize (corn), with traditional beer being brewed from maize. Carcinogenic N-nitrosamines in traditional beer were suggested as a cause of SCC of the oesophagus, with Fusarium moniliforme, a corn saprophyte, thought to play a role. OBJECTIVES: To confirm the presence of N-nitrosamines in traditional beer and demonstrate a mechanism for the oncogenesis of oesophageal carcinoma. METHODS: Analysis by high-performance liquid chromatography was conducted for the identification of nitrosamines in traditional beer samples, and molecular docking studies were employed to predict the affinity between N-nitrosamines and the S100A2 protein. RESULTS: Carcinogenic N-nitrosamines were identified in all six samples of traditional beer examined (N=18 analyses), and docking studies confirmed a high affinity of the nitrosamine N-nitrosopyrrolidone with the S100A2 protein. This may result in the altered expression of the S100A2 protein, leading to tumour progression and prognosis. CONCLUSION: It is suggested that carcinogenic N-nitrosamines in traditional beer are a major factor in the causation of SCC of the oesophagus in black South Africans. N-nitrosamines have been shown to produce cancer experimentally, but there has not been conclusive epidemiological evidence that N-nitrosamines are carcinogenic to humans. This study is the first to demonstrate the potential link between N-nitrosamines and a human tumour.


Assuntos
Cerveja/análise , Carcinoma de Células Escamosas/induzido quimicamente , Neoplasias Esofágicas/induzido quimicamente , Nitrosaminas/efeitos adversos , População Negra , Carcinógenos , Carcinoma de Células Escamosas/etnologia , Fatores Quimiotáticos/metabolismo , Cromatografia Líquida de Alta Pressão , Neoplasias Esofágicas/etnologia , Humanos , Simulação de Acoplamento Molecular , N-Nitrosopirrolidina/farmacologia , Nitrosaminas/análise , Nitrosaminas/farmacologia , Proteínas S100/metabolismo , África do Sul
11.
AAPS PharmSciTech ; 16(4): 771-86, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25549792

RESUMO

A menthol-based solid dispersion was designed to improve the intrinsic solubility of the poorly soluble sulfamethoxazole- a class II drug molecule of Biopharmaceutics Classification System (BCS) displaying widespread antibacterial activity. Solid dispersions of menthol and sulfamethoxazole were compressed with hydroxypropyl methylcellulose (HPMC) into suitable sulfamethoxazole-loaded matrix tablets for oral drug delivery. The sulfamethoxazole-loaded solid dispersions and compressed tablets were characterized for their physicochemical and physicomechanical properties such as changes in crystallinity, melting point, molecular transitions, and textural analysis for critical analysis of their effects on the solubility and dissolution of sulfamethoxazole. The formulations were further evaluated for swelling, degradation, solubility, and in vitro drug release behavior. In vitro drug release from the sulfamethoxazole-loaded matrix tablets displayed a minimum and maximum fractional release of 0.714 and 0.970, respectively. The tablets further displayed different release rate profiles over the study periods of 12, 16, 48, and 56 h which were attributed to the varying concentrations of menthol within each formulation. Menthol was determined as a suitable hydrophilic carrier for sulfamethoxazole since it functioned as a solubilizing and release-retarding agent for improving the solubility and dissolution of sulfamethoxazole as well as controlling the rate at which it was released.


Assuntos
Mentol/química , Sulfametoxazol/química , Comprimidos , Administração Oral , Teste de Materiais , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Sulfametoxazol/administração & dosagem
12.
Curr Drug Deliv ; 12(3): 282-98, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25601062

RESUMO

This review highlights recent interests and applications of disulphide and thiol chemistry in creating contemporary macromolecular designs. Due to the chemical nature of disulphides and thiols a wide range of chemical species react with these functional groups to yield a variety of polymers extending their applications in chemical, biological, physical, material engineering and material sciences. The review aims to illustrate the versatility and demonstrate the potential of thiol-based chemistries. The focus is on exploring bio-cleavable disulphides and linking by "clicking" thiols via thiol/other functional group exchange reactions. Thiol synthesis, modification and functionalization are demonstrated to be highly attractive and efficient in polymer and material science which in turn have immense application in biological therapeutics and drug delivery. The review also illustrates the remarkable pliability of synthetic and natural approaches to designing, optimizing and functionalizing nanostructures and conjugates by thiol chermistry modification. The examples quoted in the review illustrate the power and versatility of thiols for site specific functionalization, the construction of complex macromolecules and the generation of both biodegradable disulphides and non-biodegradable bonds which are the tools for constructing specific therapeutic/drug delivery systems. In addition, the ability of thiols to react with various functional groups found in a variety of polymer science materials and biological entities such as peptide and related structures will also be demonstrated. Despite of the fact that research efforts in thiol chemistry are still at the early stages, it is likely that its true potential will be developed.


Assuntos
Sistemas de Liberação de Medicamentos , Desenho de Fármacos , Polímeros/química , Animais , Dissulfetos/química , Humanos , Nanoestruturas , Peptídeos/administração & dosagem , Compostos de Sulfidrila/química
13.
Drug Dev Ind Pharm ; 41(8): 1274-87, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25109400

RESUMO

CONTEXT AND OBJECTIVE: The aim of this study was to develop, characterize and evaluate a mucoadhesive caplet resulting from a polymeric blend (polymeric caplet) for intravaginal anti-HIV-1 delivery. MATERIALS AND METHODS: Poly(lactic-co-glycolic) acid, ethylcellulose, poly(vinylalcohol), polyacrylic acid and modified polyamide 6, 10 polymers were blended and compressed to a caplet-shaped device, with and without two model drugs 3'-azido-3'-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Thermal analysis, infrared spectroscopy and microscopic analysis were carried out on the caplets employing temperature-modulated DSC (TMDSC), Fourier transform infra-red (FTIR) spectrometer and scanning electron microscope, respectively. In vitro and in vivo drug release analyses as well as the histopathological toxicity studies were carried out on the drug-loaded caplets. Furthermore, molecular mechanics (MM) simulations were carried out on the drug-loaded caplets to corroborate the experimental findings. RESULTS AND DISCUSSION: There was a big deviation between the Tg of the polymeric caplet from the Tg's of the constituent polymers indicating a strong interaction between constituent polymers. FTIR spectroscopy confirmed the presence of specific ionic and non-ionic interactions within the caplet. A controlled near zero-order drug release was obtained for AZT (20 d) and PSS (28 d). In vivo results, i.e. the drug concentration in plasma ranged between 0.012-0.332 mg/mL and 0.009-0.256 mg/mL for AZT and PSS over 1-28 d. CONCLUSION: The obtained results, which were corroborated by MM simulations, attested that the developed system has the potential for effective delivery of anti-HIV-agents.


Assuntos
Fármacos Anti-HIV/química , Sistemas de Liberação de Medicamentos/métodos , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Polímeros/química , Adesivos Teciduais/química , Adesividade/efeitos dos fármacos , Administração Intravaginal , Animais , Fármacos Anti-HIV/administração & dosagem , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Infecções por HIV/patologia , Estrutura Molecular , Polímeros/administração & dosagem , Suínos , Adesivos Teciduais/administração & dosagem
14.
Pharm Dev Technol ; 20(7): 854-862, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24946794

RESUMO

Ocular diseases of the anterior segment of the eye are increasing and the development of novel drug delivery systems for improved treatment is necessary. The aim of this study was therefore to design and evaluate an instantly-soluble solid eye drop (ISED) for topical ophthalmic drug delivery of the model drug timolol maleate. The porous nature of the lyophilized ISED resulted in rapid fluid ingression, immediate hydration, and dissolution of the ocular matrix. The ISED was lyophilized employing hydroxypropylcellulose and pluronic® F68 as the matrix forming polymers. Polyacrylic acid sodium enhanced the solubility of the ISED, di-glycine, an anti-collapsing agent, while maltodextrin improved the matrix resilience. A statistical design was employed for optimizing the texture, disintegration, and the mean dissolution time (MDT50%) of the ISED. Results revealed that a robust rapidly disintegrating ISED was produced with the fastest disintegration time recorded at 0.20 s and drug release between 79 and 96%. In addition, improved corneal drug permeation was observed compared to pure timolol dispersion. The maltodextrin concentration significantly affected the ISED matrix resilience (p = 0.007) and pluronic F68 had a greater impact on disintegration time (p = 0.000) and MDT (p = 0.000). The ISED formulation may be a promising alternative to the use of liquid eye drops for topical ophthalmic drug delivery.

15.
AAPS PharmSciTech ; 15(6): 1476-89, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24984920

RESUMO

This study focused on the synthesis and characterization of a natural polymeric system employing the interpenetrating polymer network (IPN) comprising curcumin as a bioactive. Biopolymers and actives such as chitosan, hypromellose, citric acid, genipin, and curcumin were used to develop an effective, biodegradable, and biocompatible film employed therapeutically as a wound healing platform. The semi-IPN films were investigated for their physicochemical, physicomechanical, and biological properties by quantification by FTIR, DSC, and Young's modulus. Following characterization, an optimum candidate formulation was produced whereby further in vitro and ex vivo studies were performed. Results revealed a burst release occurring at the first hour with 1.1 mg bioactive released when in contact with the dissolution medium and 2.23 mg due to bioactive permeation through the skin, thus suggesting that the lipophilic nature of skin greatly impacted the bioactive release rate. Furthermore, chemical and mechanical characterization and tensile strength analysis revealed that the degree of crosslinking and concentration of polymeric material used significantly influenced the properties of the film.


Assuntos
Quitosana/síntese química , Curcumina/administração & dosagem , Administração Cutânea , Animais , Varredura Diferencial de Calorimetria , Química Farmacêutica , Quitosana/análogos & derivados , Reagentes de Ligações Cruzadas/química , Curcumina/química , Curcumina/metabolismo , Módulo de Elasticidade , Iridoides/química , Cinética , Permeabilidade , Ratos Sprague-Dawley , Pele/metabolismo , Absorção Cutânea , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Tecnologia Farmacêutica/métodos , Temperatura , Resistência à Tração , Água/química
16.
J Pharm Sci ; 103(8): 2211-30, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24985412

RESUMO

Wound healing is a complex and dynamic process that involves the mediation of many initiators effective during the healing process such as cytokines, macrophages and fibroblasts. In addition, the defence mechanism of the body undergoes a step-by-step but continuous process known as the wound healing cascade to ensure optimal healing. Thus, when designing a wound healing system or dressing, it is pivotal that key factors such as optimal gaseous exchange, a moist wound environment, prevention of microbial activity and absorption of exudates are considered. A variety of wound dressings are available, however, not all meet the specific requirements of an ideal wound healing system to consider every aspect within the wound healing cascade. Recent research has focussed on the development of smart polymeric materials. Combining biopolymers that are crucial for wound healing may provide opportunities to synthesise matrices that are inductive to cells and that stimulate and trigger target cell responses crucial to the wound healing process. This review therefore outlines the processes involved in skin regeneration, optimal management and care required for wound treatment. It also assimilates, explores and discusses wound healing drug-delivery systems and nanotechnologies utilised for enhanced wound healing applications.


Assuntos
Bandagens , Materiais Biocompatíveis/química , Polímeros/química , Fenômenos Fisiológicos da Pele , Cicatrização , Animais , Terapia Baseada em Transplante de Células e Tecidos , Sistemas de Liberação de Medicamentos , Humanos , Nanomedicina , Nanoestruturas/química
17.
AAPS PharmSciTech ; 15(5): 1292-306, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24920521

RESUMO

The current study involved the development of a novel sustained release crosslinked semi-IPN xerogel matrix tablet prepared by chemical crosslinking of poly(ethylene) oxide (PEO) and gellan gum (GG) employing epichlorohydrin (EPI) as crosslinker. A Box-Behnken design was employed for the statistical optimization of the matrix system to ascertain the ideal combination of native polymeric and crosslinking agents. Characterization studies were performed by employing standard polymer characterization techniques such as Fourier transform infrared spectrometry, differential scanning calorimetry, and scanning electron microscopy. Formulated matrix tablets displayed zero-order release kinetics, extending over 24 h. The mechanism of drug release was primarily by swelling and surface erosion. Crosslinked semi-IPN xerogel matrix tablets were compared to non-crosslinked polymer blends; results from the study conducted showed that the physiochemical properties of the PEO and GG were sufficiently modified to allow for sustained release of sulpiride with a 100% drug release at 24 h in a controlled manner as compared to non-crosslinked formulations which displayed further release beyond the test period. Crosslinked formulations displayed water uptake between 450 and 500% indicating a controlled rate of swelling and erosion allowing for sustained release. Surface morphology of the crosslinked system depicted a porous structure formed by interpenetrating networks of polymers, allowing for a greater degree of controlled penetration into the system affording it the ability to sustain drug release. Therefore, conclusively, based on the study performed, crosslinked PEO-GG allows for the sustained release of sulpiride from a hydrophilic semi-IPN xerogel matrix system.


Assuntos
Antipsicóticos/administração & dosagem , Reagentes de Ligações Cruzadas/química , Epicloroidrina/química , Polietilenoglicóis/química , Polissacarídeos Bacterianos/química , Sulpirida/administração & dosagem , Algoritmos , Antipsicóticos/química , Química Farmacêutica , Preparações de Ação Retardada , Excipientes , Testes de Dureza , Pós , Solubilidade , Sulpirida/química
18.
J Pharm Pharmacol ; 66(4): 490-506, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24635554

RESUMO

OBJECTIVES: The human eye is a unique and intricate structure which has made drug delivery to the eye a formidable undertaking. Anterior-segment eye diseases are ubiquitous, especially among elderly patients, and conventional eye drops, although a first-choice dosage form, are not always an efficient treatment option. The development of novel drug delivery systems for improved treatment is therefore imperative. KEY FINDINGS: In an attempt to circumvent the obstacles presented by the structure of the eye, advanced systems such as ocular mini-tablets have been developed. In this review, a concerted effort has been made to provide a detailed overview of topically administered ocular mini-tablets and other solid devices for drug delivery to the anterior segment of the eye. These mini-tablets have been shown in vitro and in vivo to have significant advantages in comparison with liquid preparations. This is a step toward attaining better patient convenience and compliance, which are critical factors. SUMMARY: Solid ophthalmic dosage forms have several advantages that can contribute to assisting with patient compliance and, ultimately, effective disease treatment. In addition to the challenges associated with topical ocular drug delivery, the shortcomings of conventional eye drops, advantages of mini-tablets, and improvements to date to these systems are discussed. The requirement for further advancements in the ocular field is also emphasized.


Assuntos
Segmento Anterior do Olho/efeitos dos fármacos , Comprimidos/administração & dosagem , Administração Tópica , Sistemas de Liberação de Medicamentos/métodos , Humanos
19.
Int J Pharm ; 466(1-2): 296-306, 2014 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-24607446

RESUMO

The purpose of this study was to investigate the in-depth pharmaceutical properties and in vivo behavior of a novel lyophilized rapidly dissolving solid ocular matrix (RD-SOM) as a 'solid eye drop' formulation comprising timolol maleate as the model drug. Thermal and molecular transition analysis displayed similar findings with no incompatibility between formulation components. Porositometric studies confirmed the presence of interconnecting pores across the matrix surface. The HETCAM test indicated an irritation score of 0 with the inference of good tolerability for the RD-SOM in the New Zealand White albino rabbit eye model. Ex vivo permeation across excised rabbit cornea showed an improved steady state drug flux (0.00052 mg cm(-2)min(-1)) and permeability co-efficient (1.7 × 10(-4)cmmin(-1)) for the RD-SOM compared to pure drug and a marketed eye drop preparation. UPLC analysis quantitatively separated timolol maleate and the internal standard (diclofenac sodium) and gamma irradiation was used as a terminal sterilization procedure. In vivo results revealed a peak concentration of timolol was reached at 104.9 min. In the case of a typical eye drop formulation a lower Cmax was obtained (1.97 ug/mL). Level A point-to-point IVIVC plots via the Wagner-Nelson method revealed a satisfactory R(2) value of 0.84. In addition, the biodegradability and ocular compatibility of the RD-SOM was confirmed by histopathological toxicity studies.


Assuntos
Anti-Hipertensivos/administração & dosagem , Sistemas de Liberação de Medicamentos , Olho/metabolismo , Soluções Oftálmicas/administração & dosagem , Timolol/administração & dosagem , Administração Oftálmica , Animais , Anti-Hipertensivos/farmacocinética , Embrião de Galinha , Membrana Corioalantoide/efeitos dos fármacos , Técnicas In Vitro , Soluções Oftálmicas/farmacocinética , Permeabilidade , Coelhos , Solubilidade , Timolol/farmacocinética
20.
Int J Nanomedicine ; 9: 589-613, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24489467

RESUMO

Nanotechnology, although still in its infantile stages, has the potential to revolutionize the diagnosis, treatment, and monitoring of disease progression and success of therapy for numerous diseases and conditions, not least of which is cancer. As it is a leading cause of mortality worldwide, early cancer detection, as well as safe and efficacious therapeutic intervention, will be indispensable in improving the prognosis related to cancers and overall survival rate, as well as health-related quality of life of patients diagnosed with cancer. The development of a relatively new field of nanomedicine, which combines various domains and technologies including nanotechnology, medicine, biology, pharmacology, mathematics, physics, and chemistry, has yielded different approaches to addressing these challenges. Of particular relevance in cancer, nanosystems have shown appreciable success in the realm of diagnosis and treatment. Characteristics attributable to these systems on account of the nanoscale size range allow for individualization of therapy, passive targeting, the attachment of targeting moieties for more specific targeting, minimally invasive procedures, and real-time imaging and monitoring of in vivo processes. Furthermore, incorporation into nanosystems may have the potential to reintroduce into clinical practice drugs that are no longer used because of various shortfalls, as well as aid in the registration of new, potent drugs with suboptimal pharmacokinetic profiles. Research into the development of nanosystems for cancer diagnosis and therapy is thus a rapidly emerging and viable field of study.


Assuntos
Técnicas Biossensoriais/instrumentação , Diagnóstico por Imagem/métodos , Nanomedicina/instrumentação , Nanopartículas/uso terapêutico , Neoplasias/diagnóstico , Neoplasias/terapia , Antineoplásicos/uso terapêutico , Humanos , Nanomedicina/métodos
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