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1.
Colloids Surf B Biointerfaces ; 190: 110902, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32143010

RESUMO

Topical administration of corticosteroids is the cornerstone treatment of anterior uveitis, but poor corneal penetration and retention cause hindrance in their therapeutic utility. The conventional eye drops are less valuable in conditions where inflammation reaches deeper regions of the eye. Therefore, there is a clear need for an effective drug delivery system, which can increase corticosteroid penetration after topical application. To address this, cationic nanostructured lipid carriers of the drug triamcinolone acetonide (cTA-NLC) were prepared. The cTA-NLC were prepared by a hot microemulsion method and evaluated for drug release, permeation, cell uptake, cytotoxicity, anti-inflammatory activity and ocular irritancy. The cTA-NLC are nanometric in size (< 200 nm), with a zeta potential of about +35 mv and % drug EE of 88 %. The nanocarriers exhibited slow and sustained release of around 84 % in 24 h and transcorneal drug permeation of 51 % in 8 h. The nanocarriers exhibited no cytotoxicity (% cell viability of>90 %). The cell uptake study showed that nanocarriers could retain inside the cells for 24 h. The developed formulation could significantly reduce the TNF-α level in LPS induced inflamed cells. The studies indicated that cTA-NLC could be a promising option for the topical treatment of uveitis.

2.
Expert Opin Drug Deliv ; 17(2): 255-273, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31990219

RESUMO

Background: The research work endeavors to develop a liquid dosage form of an efficacious antipsoriatic drug, i.e., coal tar, but having problems like variability and patient noncompliance.Methods: The emulsion was prepared by the wet gum method from standardized coal tar. The optimized lotion obtained after sequential experimental designs was characterized for various dosage form and/or coal tar-related properties including efficacy.Results: The formulation deposited more coal tar in the unit area of rat skin than marketed lotions. The efficacy of lotion in psoriasis animal models was more or equivalent to marketed lotions. The formulation showed one compartment body model dermatokinetics, nonirritancy after repeated applications, and stability at room conditions for a year.Conclusion: The formulation with desired attributes was successfully developed.

3.
Int J Pharm ; 576: 118977, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31870953

RESUMO

Silver Sulphadiazine (SSD) is an effective antibacterial agent considered as the gold standard for burn wound treatment. The present study aimed to investigate EO-based organogel (SSD-EOOG) as an effective carrier system for SSD delivery in burn wound management employing Quality by Design (QbD) paradigm. The organogel-based formulations were prepared employing QbD-oriented approach and further evaluated for in vivo efficacy and stability. The developed formulations were characterized for particle size, drug content, morphology, in vitro drug release, skin safety studies, ex vivo permeation, skin retention, textural analysis and pharmacodynamic studies in murine burn wound model. I-optimal mixture design was employed for optimization and evaluating different critical quality attributes (CQAs). The optimized formulation exhibited particle size of 256.5 nm with enhanced permeation (72.33 ± 1.73%) and retention (541.20 ± 22.16 µg/cm2) across skin barrier as compared to SSD-MKT. The pharmacodynamic results proved superior therapeutic efficacy of SSD-EOOG in topical burn wounds inflicted with MRSA bacterium. The results indicated wound contraction rate (78.23 ± 5.65%) and faster re-epithelialization in SSD-EOOG treated group. The present study concluded that egg oil based organogel promoted therapeutic efficacy of SSD for burn wound treatment.

4.
J Pharm Sci ; 108(12): 3879-3889, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31568776

RESUMO

The cost, side effects, and patient compliance-related issues of topically effective imiquimod have prevented its widespread acceptance. The present work intends to evaluate the feasibility of overcoming the shortcomings of poorly soluble and skin-penetrating immunomodulator by using biocompatible keratolytic agent with drug-loaded hybrid vesicles. Salicylic acid was complexed with phospholipid through simple mixing and incorporated into carbopol 940 gel containing drug-loaded vesicles, prepared by thin-film hydration method. The morphology, physicochemical properties, rheological behavior, release profile, and dermatokinetics of developed gel were compared with control gel (developed gel without keratolytic agent). In ex vivo drug release studies across the rat skin, there was significant increase in the steady-state permeation flux (Jss) and skin retention of drug from developed gel in comparison with control. There was favorable change in almost every evaluated dermatokinetic parameter. The innocuous nature of control gel had not changed on addition of skin structure-altering agent. The developed gel was found to be stable at room temperature and humidity for 1 year.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31082718

RESUMO

A simple, rapid, accurate, reproducible and sensitive reverse phase HPLC method for the estimation of fusidic acid (FA) by means of Analytical Quality by Design (AQbD) was the aim of the present study. Initially, the vital pre-requisites for AQbD like analytical method target profile and critical analytical attributes (CAAs) like theoretical plates, tailing factor and percent assay were defined. An octadecyl silyl silica C18 column with a packing size of 5 µm was employed and the detection was performed at 235 nm using UV-detector. The separation was performed with isocratic elution employing mixture of methanol: acetonitrile (5: 95, v/v) and an aqueous phase with pH of 2.8 containing 0.1% orthophosphoric acid in the ratio of 60: 40 (v/v). Ishikawa fish-bone diagram provided the basis of the variation in CAAs with various inputs. Taguchi Design was selected as the initial screening design to select critical method parameters (CMPs) affecting method development and Central Composite Design (CCD) was further applied for systematic optimization of chromatographic method by evaluating CAAs. Crucial parameters viz. limit of detection, limit of quantification, specificity, linearity and sensitivity were employed to validate the method in accordance with the ICH guidelines. Stress degradation studies were performed and the developed method was able to successfully differentiate the degraded products from the parent drug, that too in a topical gel. In conclusion, the findings of the present study validated the utility of AQbD in the systematic design of a liquid chromatographic method with fine sensitivity for FA estimation in medicinal products.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , Cromatografia de Fase Reversa/métodos , Cromatografia de Fase Reversa/normas , Ácido Fusídico , Ácido Fusídico/análise , Ácido Fusídico/química , Ácido Fusídico/farmacocinética , Cinética , Limite de Detecção , Modelos Lineares , Modelos Químicos , Reprodutibilidade dos Testes , Projetos de Pesquisa
6.
J Chromatogr Sci ; 57(7): 583-591, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31095670

RESUMO

For a new immune modulator imiquimod, various liquid chromatography methods have been described in literature but all of them are deficient in one or other aspects of complete method development. The present work intends to develop and validate the stability indicating reverse phase high performance liquid chromatographic (HPLC) method. The isocratic flow of mobile phase comprising equal volume ratio of acetate buffer BP pH 3.7 and acetonitrile at the rate of 1.5 mL/min through the C-18 column at 25°C lead to elution of drug around 2.3 min when analyzed at 244 nm using UV-detector. The linear regression equation in calibration plot was y = 61632×-1224 with 0.9992 coefficient of determination (r2). The percent relative standard variation (% RSD) in peak area at low, mid and high region of linearity range was less than 5% in precision studies. The method was able to detect 0.039 µg/mL of drug but practical limit of quantitation (LOQ) was 1.5 µg/mL. The imiquimod molecule was stable in all except oxidizing conditions where it degraded into more polar molecule in hydrogen peroxide (H2O2) concentration dependent manner. Therefore, an analytical method capable of accurately and specifically estimating the drug in microgram range was successfully developed.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Imiquimode/análise , Imiquimode/química , Acetonitrilos , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes
7.
AAPS PharmSciTech ; 20(5): 169, 2019 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-31004249

RESUMO

The aim of the present study was to explore the therapeutic efficacy of microemulsion-based delivery of histidine-capped silver nanoparticles in eradicating Klebsiella pneumoniae-induced burn wound infection. The developed microemulsion was characterized on the basis of differential light scattering, phase separation, refractive index, and specific conductance. Emulgel was prepared and characterized on the basis of thixotropy, texture, differential scanning calorimetry, and release kinetics. Emulgel was further evaluated in skin irritation and in vivo studies, namely full-thickness K. pneumoniae-induced burn wound infection treatment via topical route. Efficacy of treatment was evaluated in terms of bacterial load, histopathology, wound contraction, and other infection markers. The developed emulgel provided significant in vivo antibacterial activity of histidine-capped silver nanoparticle preparations via topical route and resulted in reduction in bacterial load, wound contraction, and enhanced skin healing as well as decrement of inflammatory markers such as malondialdehyde, myeloperoxidase, and reactive nitrogen intermediate compared to untreated animals. The present study encourages the further employment of histidine-capped silver nanoparticles along with microemulsion-based drug delivery system in combating antibiotic-resistant topical infections.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/uso terapêutico , Queimaduras/complicações , Histidina/administração & dosagem , Histidina/uso terapêutico , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae , Compostos de Prata/administração & dosagem , Compostos de Prata/uso terapêutico , Infecção dos Ferimentos/tratamento farmacológico , Administração Tópica , Animais , Sistemas de Liberação de Medicamentos , Emulsões , Feminino , Géis , Infecções por Klebsiella/microbiologia , Nanopartículas Metálicas , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Nanopartículas/uso terapêutico , Infecção dos Ferimentos/microbiologia
8.
Int J Biol Macromol ; 133: 1142-1155, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31004631

RESUMO

Fungal keratitis (FK) is treated by topical natamycin (Nat) which is an effective antifungal agent. However, it has numerous therapeutic limitations i.e. toxicity, tolerance, need of frequent dosing and patient incompliance. The aim of the present study was to develop Nat loaded trimethyl chitosan (TMC) coated mucoadhesive cationic niosomes (Muc-Cat-Nios) for prolonged and effective delivery to eyes. Niosomes were prepared using thin film hydration method and optimized using a Box-Behnken design (BBD) with the help of Design-Expert® Software. Three independent variables were considered: amount of Span 60 (X1), amount of Cholesterol [Chol(X2)] and TMC concentration (X3). The encapsulation efficiency (R1: EE%), vesicle size (R2: VS) and Zeta potential (R3: ZP) were selected as dependent variables or responses. The optimized Nios displayed spherical shape, 1034.14 nm vesicle size and 81.76% EE. Nat loaded niosomes were incubated with TMC to get mucoadhesive cationic vesicular system. Uncoated and TMC coated niosomes were characterized for mucoadhesive properties, in vitro drug release, rheological behaviour, and ex vivo permeation studies. Cationic Nios showed greater mucoadhesive potential that provided drug release for a long period of time. The promising outcomes suggest that natamycin delivery using cationic mucoadhesive niosomes could be employed for the effective treatment of fungal keratitis.


Assuntos
Portadores de Fármacos/química , Engenharia , Lipossomos/química , Membrana Mucosa/química , Adesividade , Animais , Quitosana/química , Córnea/metabolismo , Liberação Controlada de Fármacos , Cabras , Natamicina/química , Natamicina/metabolismo , Reologia , Propriedades de Superfície
9.
AAPS PharmSciTech ; 20(4): 156, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30927154

RESUMO

The present research work explored the possibility of harnessing the benefits of vesicular carriers for overcoming imiquimod-associated complaints or side effects. Hybrid vesicles were prepared by the most common and easily scalable method, i.e., thin film hydration. The chaffing of myriad of factors, both process and material related, affecting the desirable attributes of conceived vesicles, was performed through Taguchi design. Based upon the analysis of Pareto chart and prior experiences, concentration of phospholipid and poloxamer 407 was selected for optimization by 2 levels, 13 run central composite design (CCD). The optimized hybrid vesicles contained 1% w/v phospholipid and 3% w/v poloxamer 407. The optimized hybrid vesicles were incorporated into the 3% w/v carbopol 940 gel and characterized for morphology, physicochemical properties, and rheological behavior. The release (%) and skin retention (% of total dose) across rat skin from gel at same amount of formulation was more than Imiquad®. The gel delivered the loaded cargo, preferably, in the viable region of skin and formed local depot in confocal microscopic studies. The gel followed one compartment open body dermatokinetic model in rat skin. There was not any harmful effect on the mice skin after repeated applications. The gel was stable at room conditions for 1 year.


Assuntos
Portadores de Fármacos/síntese química , Portadores de Fármacos/farmacocinética , Imiquimode/síntese química , Imiquimode/farmacocinética , Absorção Cutânea/efeitos dos fármacos , Adjuvantes Imunológicos , Animais , Estabilidade de Medicamentos , Feminino , Géis/química , Masculino , Camundongos , Técnicas de Cultura de Órgãos , Tamanho da Partícula , Fosfolipídeos/química , Fosfolipídeos/farmacocinética , Ratos , Reologia , Pele/efeitos dos fármacos , Pele/metabolismo , Absorção Cutânea/fisiologia
10.
Expert Opin Drug Deliv ; 16(4): 377-396, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30871388

RESUMO

INTRODUCTION: The dermatophytosis are the infections, which are the most common infections worldwide, with the serious problem of high recurrence. These are characterized by invasion and multiplication of various species of dermatophytes in keratinized tissues that can affect skin, hair, and nails. AREAS COVERED: This article aims to gather information about novel strategies for effective treatment of dermatophytosis by incorporating antifungals into nanoformulations to overcome the limitations of the conventional treatment strategies. Updates related to nanosystems and research progress regarding the animal and clinical studies are also included. The current treatment options for dermatophytosis, along with the marketed formulations and patents, are also highlighted. EXPERT OPINION: For treating dermatophytosis, several therapeutic interventions are available which provide good clinical cure rates, but they have some demerits, including resistance to the antifungal agents and adverse effects associated with them. In recent years, efforts have been documented to incorporate various antifungal agents into novel carriers in order to offer better therapeutic action and overcome the limitations of the conventional treatment strategies for dermatophytosis. The success has been achieved in obtaining these formulations with enhanced antifungal activity, prolonged retention of drug, improved efficacy, increased skin penetration of the drug, and sustained release of drug.

11.
AAPS PharmSciTech ; 20(3): 100, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30721373

RESUMO

Beta-carotene (BC), a red-colored pigment found in plants and animals, is one of the most extensively investigated carotenoids due to its provitamin-A, antioxidant, and anticancer properties. The anticancer activity of BC through oral administration is severely affected due to its low bioavailability and oxidative degradation. The present study aimed to formulate and characterize solid lipid nanoparticles (SLNs) of BC for enhanced bioavailability and therapeutic efficacy. Beta-carotene-loaded solid lipid nanoparticles (BC-SLNs) were prepared employing different combinations of glyceryl monostearate and gelucire. The characterization studies were performed for particle size, morphology, release behavior, and stability. BC-SLNs were also studied for in vitro cytotoxicity in human breast cancer cell lines (MCF-7) and pharmacokinetic studies in Wistar rats. The cytotoxicity studies confirmed that encapsulation of BC within the lipid bilayers of nanoparticles did not affect its anticancer efficacy. An improved anticancer activity was observed in BC-SLNs as compared to the free BC. BC-SLNs enhanced the bioavailability of BC on oral administration by sustaining its release from the lipid core and prolongation of circulation time in the body. Similarly, area under the curve (AUCtotal) enhanced 1.92-times more when BC was incorporated into SLNs as compared to free BC. In conclusion, solid lipid nanoparticles could be an effective and promising strategy to improve the biopharmaceutical properties of carotenoids for anticancer effects.


Assuntos
Antineoplásicos/administração & dosagem , Portadores de Fármacos/administração & dosagem , Nanopartículas/administração & dosagem , beta Caroteno/administração & dosagem , Administração Oral , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Disponibilidade Biológica , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Portadores de Fármacos/química , Glicerídeos/administração & dosagem , Glicerídeos/química , Glicerídeos/metabolismo , Humanos , Lipídeos , Células MCF-7 , Masculino , Nanopartículas/química , Nanopartículas/metabolismo , Tamanho da Partícula , Ratos , Ratos Wistar , beta Caroteno/química , beta Caroteno/metabolismo
12.
AAPS PharmSciTech ; 20(2): 74, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30631981

RESUMO

The present study aimed to orally deliver methylthioadenosine (MTA) to the brain employing solid lipid nanoparticles (SLNs) for the management of neurological conditions like multiple sclerosis. The stearic acid-based SLNs were below 100 nm with almost neutral zeta potential and offered higher drug entrapment and drug loading. Cuprizone-induced demyelination model in mice was employed to mimic the multiple sclerosis-like conditions. It was observed that the MTA-loaded SLNs were able to maintain the normal metabolism, locomotor activity, motor coordination, balancing, and grip strength of the rodents in substantially superior ways vis-à-vis plain MTA. Histopathological studies of the corpus callosum and its subsequent staining with myelin staining dye luxol fast blue proved the potential of MTA-loaded SLNs in the remyelination of neurons. The pharmacokinetic studies provided the evidences for improved bioavailability and enhanced bioresidence supporting the pharmacodynamic findings. The studies proved that SLN-encapsulated MTA can be substantially delivered to the brain and can effectively remyelinate the neurons. It can reverse the multiple sclerosis-like symptoms in a safer and effective manner, that too by oral route.


Assuntos
Encéfalo/efeitos dos fármacos , Desoxiadenosinas/administração & dosagem , Sistemas de Liberação de Medicamentos , Atividade Motora/efeitos dos fármacos , Esclerose Múltipla/tratamento farmacológico , Nanopartículas/administração & dosagem , Ácidos Esteáricos/administração & dosagem , Tionucleosídeos/administração & dosagem , Administração Oral , Animais , Disponibilidade Biológica , Encéfalo/patologia , Desoxiadenosinas/farmacocinética , Camundongos , Ratos , Ratos Wistar , Tionucleosídeos/farmacocinética
13.
Drug Deliv Transl Res ; 9(4): 748-763, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30652257

RESUMO

Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) have been a major cause of morbidity in thermally injured patients. The skin barrier gets disrupted and loss of immunity further makes burn sites an easy target for bacterial colonization. In the current study, combined potential of lipid-polymer hybrid nanoparticles (LPHNs) with fusidic acid was explored as a promising strategy toward combating resistant bacteria in burn wound infection sites. The developed systems exhibited particle size (310.56 ± 5.22 nm), zeta potential (24.3 ± 4.18 mV) and entrapment efficiency (78.56 ± 3.56%) with a spherical shape. The hybrid nanoparticles were further gelled into carbopol and demonstrated better permeation (76.53 ± 1.55%) and retention characteristics (56.41 ± 4.67%) as compared to the conventional formulation. The topical delivery of FA into the skin layers by FA-LPHN gel was found to be significantly higher (p < 0.05) compared to FA-CC. The in vivo potential was further assessed in murine burn wound model inflicted with MRSA 33591 bacterium with the determination of parameters like bacterial burden, wound contraction, morphological and histopathological examination of wounds. The bacterial count decreased drastically in FA-LPHN gel group (5.22 log CFU/mL) on day 3 with significant difference in comparison to FA-CC. The wound size reduction in FA-LPHN gel (68.70 ± 3.65%) was higher as compared to FA-CC (73.30 ± 4.23%) and control groups (83.30 ± 4.40%) on day 5. The current study presents a safe and effective formulation strategy for the treatment of MRSA-infected burn wounds by providing moist environment and prevention from bacterial infection.


Assuntos
Queimaduras/tratamento farmacológico , Portadores de Fármacos/administração & dosagem , Ácido Fusídico/administração & dosagem , Staphylococcus aureus Resistente à Meticilina , Nanopartículas/administração & dosagem , Pele/metabolismo , Infecções Estafilocócicas/tratamento farmacológico , Infecção dos Ferimentos/tratamento farmacológico , Animais , Queimaduras/imunologia , Queimaduras/microbiologia , Citocinas/imunologia , Portadores de Fármacos/farmacocinética , Feminino , Ácido Fusídico/farmacocinética , Géis , Lipídeos/administração & dosagem , Lipídeos/farmacocinética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Camundongos Endogâmicos BALB C , Polímeros/administração & dosagem , Polímeros/farmacocinética , Ratos Wistar , Pele/efeitos dos fármacos , Pele/imunologia , Absorção Cutânea , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Infecção dos Ferimentos/imunologia , Infecção dos Ferimentos/microbiologia
14.
Expert Opin Drug Deliv ; 16(2): 101-112, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30582385

RESUMO

INTRODUCTION: Actinic keratosis is one of the most common disorder characterized by erythematic and generally attached scaly lesions which are present either alone or in clusters. World Health Organization defines actinic keratosis as a common intraepidermal neoplasm of sun-damaged skin, characterized by variable atypia of keratinocytes. AREAS COVERED: At the beginning of the 20th century, a new immunomodulator molecule, imiquimod, appears in the market for the treatment of actinic keratosis but suffers from the pitfalls of the conventional approach of dosage form preparation including high dose, poor stability and more side effects. The present article attempts to compile the scatter information related to actinic keratosis and imiquimod at one place. The special emphasis will be made on the information available in various research articles and patents with respect to the efforts made for overcoming shortcomings associated with imiquimod by novel drug delivery or other approaches. EXPERT OPINION: The conventional drug delivery systems are unsuccessful to improve the actinic keratosis. The patient acceptance and compliance with these treatments are generally poor due to associated side effects, poor cosmetic outcomes and high costs. Therefore, several available and reported novel therapeutic approaches are being developed in order to provide better action.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Imiquimode/uso terapêutico , Ceratose Actínica/tratamento farmacológico , Humanos , Cooperação do Paciente , Pele/metabolismo
15.
AAPS PharmSciTech ; 19(7): 3187-3198, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30143947

RESUMO

Celecoxib (CXB), a COX-2 inhibitor, is primarily indicated for long-term treatment of rheumatoid arthritis (RA). The effective therapeutic efficacy of CXB on RA via oral administration shows adverse systemic complications, and therefore, local application of CXB has been recommended. The aim of the present study was to develop and characterize solid lipid nanoparticles (SLNs) with enhanced skin permeation potential of CXB. The particle size, polydispersity index (PDI), and percentage drug entrapment (PDE) of the developed SLNs (CXB-SLNs) were found to be 240 nm, < 0.3, and ~ 86% respectively. The developed SLNs exhibited sustained release up to 70% at the end of 48 h. Drug permeation was found to be 45% for SLN gel and 31% for conventional gel. The dermatokinetic studies also confirmed enhanced permeation of CXB in the epidermis and dermis and revealed superiority of the developed SLN gel vis-à-vis the conventional gel. Further, in the CFA-induced arthritis rat model, % arthritis index (AI) of the CXB-SLN gel formulation was found to be very less (18.54%) as compared to untreated (187.34%) and conventional gel-treated (91.61%) animals. In conclusion, the current study can provide a suitable alternative for the development of an effective topical formulation of CXB in lipid nanocarriers.


Assuntos
Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Celecoxib/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Nanopartículas/administração & dosagem , Animais , Celecoxib/química , Celecoxib/farmacocinética , Portadores de Fármacos , Adjuvante de Freund/imunologia , Lipídeos/química , Masculino , Ratos , Ratos Wistar , Pele/metabolismo
16.
Artif Cells Nanomed Biotechnol ; 46(sup2): 776-789, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29961343

RESUMO

The aim of present approach was to design and develop mannose functionalized reverse polymeric nanocomposite(s) system based on release promoter (MRPRPNs). Thus, the composition of the present formulation was optimized by employing the systematic design of experiments (DoE) for screening and optimization using L8-Array Taguchi and 3-level-3-factor Box-Behnken Design (BBD). Further, the developed formulation was observed for its preferential internalization by professional antigen presenting cells (macrophages/dendritic cells) and prompt release of loaded antigen in a pH-dependent manner. The optimized formulation was also extensively characterized for average hydrodynamic diameter, surface potential, poly dispersity index of reverse polymeric nanocomposite(s) which were recoded to be 189.4 ± 8.52 nm, 0.111 ± 0.024, -23.4 ± 2.0 mV, respectively; while percentage entrapment efficiency of OVA in MRPRPNs to be 60.17 ± 2.41%. The release pattern of OVA from MRPRPNs was consistent at pH 7.4. However, at acidic pH (≈5.5) where in protons (H+) are in-filtered into the core of MRPRPNs thereby generating the pressure, resultantly causing and creating the pores or disruption of the system thus allowed a prompt release (≈60-70%) of encapsulated OVA from interior to outer milieu within 1 h. MRPRPNs were preferentially internalized through receptor-mediated endocytosis and released the loaded OVA into the cytosol of RAW 264.7 cells. From the above findings, it can be concluded that reverse polymeric system could significantly be loaded with immunobioactive(s) and could potentially deliver the contents at the specific site for the better therapeutic outcome.


Assuntos
Portadores de Fármacos/química , Desenho de Drogas , Nanocompostos/química , Ovalbumina/química , Animais , Citosol/metabolismo , Liberação Controlada de Fármacos , Endocitose , Manose/química , Camundongos , Ovalbumina/imunologia , Ovalbumina/metabolismo , Células RAW 264.7
17.
Int J Pharm ; 546(1-2): 97-105, 2018 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-29715533

RESUMO

The work entails a novel strategy of formulating the lycopene loaded whey protein isolate nanoparticles (LYC-WPI-NPs) solely using the rational blend of biomacromolecule without using equipment-intensive techniques. The LYC-WPI-NPs were fabricated as a substantial drug delivery platform, with maximum entrapment, spatial and controlled release manners, exceptional plasma concentration, and perspective for discrepancy delivery of therapeutics. Prepared nano-formulations were measured in ultra-fine size (100-350 nm) with sphere-shaped. The percent lycopene entrapment of prepared LYC-WPI-NPs was estimated in the range to 50 and 65%. In vitro percent cumulative release study demonstrated deaden and extended release i.e. approximately 75% following 16th h. The in vitro percent cell survival (cytotoxicity study) of prepared nanoparticles was evaluated against MCF-7 breast cancer cells by MTT based colorimetric assay. Sub-cellular localization of lycopene when delivered by LYC-WPI-NPs was assessed by HPLC (high performance liquid chromatography). The WPI-NPs enhance the oral bioavailability of lycopene by controlling its release from nano-formulation and facilitating its absorption through lymphatic pathways. Prophylactic anticancer efficacy of LYC-WPI-NPs was evaluated thereafter on experimentally induced breast cancer animal model. Conclusively, it may quite reasonable that lycopene loaded protein nanoparticles are competent to improve the biopharmaceutical attributes of lycopene and demonstrated prophylactic anticancer activity, decrease tumor proliferation and increase the survival rate of treated animals, thus signifying their feasible usefulness in cancer therapeutic and intervention.


Assuntos
Antineoplásicos/administração & dosagem , Carotenoides/administração & dosagem , Portadores de Fármacos/administração & dosagem , Nanopartículas/administração & dosagem , Proteínas do Soro do Leite/administração & dosagem , Administração Oral , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Disponibilidade Biológica , Carotenoides/química , Carotenoides/farmacocinética , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Feminino , Suco Gástrico/química , Humanos , Secreções Intestinais/química , Licopeno , Células MCF-7 , Neoplasias Mamárias Experimentais/tratamento farmacológico , Nanopartículas/química , Ratos Wistar , Proteínas do Soro do Leite/química , Proteínas do Soro do Leite/farmacocinética
18.
Mater Sci Eng C Mater Biol Appl ; 89: 274-282, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29752099

RESUMO

Our aim was to develop multiwalled carbon nanotubes (MWCNTs)-based nanoconstructs for the codelivery of N-desmethyl tamoxifen (N-TAM) and a mild P-gp efflux inhibitor, i.e., quercetin (QT) to treat multiple drug resistant (MDR) cancer cells. The hypothesis banks on three-tier attack on the MDR mechanisms viz. drug derivatization, MWCNT permeation and P-gp inhibition. Tamoxifen was converted to N-TAM and was conjugated to carboxylated MWCNTs mediated by a biodegradable linker, i.e., tetraethylene glycol (TEG). QT was adsorbed on the conjugate to fetch the final product, i.e., N-TAM-TEG-MWCNT-QT. Spectroscopic analysis confirmed successful conjugation of N-TAM and physical adsorption of QT. The in-vitro release of N-TAM from the N-TAM-TEG-MWCNT conjugate was minimal to that of pure drug under physiological conditions, but markedly enhanced under the acidic pH of cancer cells. The developed nanometeric formulation was found to be haemo-compatible. Reduced IC50values and better cellular uptake in drug resistant MDA-MB-231 cells were observed, followed by enhanced drug availability in the systemic circulation of rodents vis-à-vis naïve drug. The smart nanosystem conferred the desired temporal drug delivery, enhanced drug efficacy, biocompatibility and conducive pharmacokinetics, which are the crucial desired attributes to tackle the increasing concern of MDR in cancer chemotherapy.


Assuntos
Portadores de Fármacos/química , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Nanotubos de Carbono/química , Quercetina/química , Tamoxifeno/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Meia-Vida , Hemólise/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Polietilenoglicóis/química , Quercetina/metabolismo , Quercetina/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Tamoxifeno/metabolismo , Tamoxifeno/farmacologia
19.
Recent Pat Antiinfect Drug Discov ; 13(2): 127-150, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29807522

RESUMO

BACKGROUND: Topical infections, involving a number of diseases such as impetigo, eczema, pustular acne, psoriasis and infected seborrheic dermatitis are one among the many challenges to health which stand out for their profound impact on human species. The treatment of topical infections has always been a difficult proposition because of the lack of efficacy of existing anti-infectives, longer period of treatment and yet incomplete recovery. The increasing emergence of antibiotic resistant bacterial strains like Staphylococcus aureus, Methicillin-Resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa undermines the need for the development of new delivery systems to enhance the therapeutic efficacy of existing topical anti-infectives. METHODS: The application of nanotechnology to medicine, or nanomedicine, is rapidly becoming a major driving force behind ongoing changes in the anti-infective field because of its interaction at the sub-atomic level with the skin tissue. The latter, in the current scenario, points towards vesicular carriers like liposomes, lipidic nanoparticles and silver nanoparticles. as the most promising drug delivery solutions for topical infection disorders. These have exhibited immense significance owing to their uniqueness to facilitate the interactions at interfaces with the barrier membranes. RESULTS: The present review summarizes the emerging efforts in combating topical infections particularly using nanomedicine based delivery systems as new tools to tackle the current challenges in treating infectious diseases. Besides, compiling various research reports, this article also includes formulation considerations, mechanisms of penetration and patents reported. CONCLUSION: Despite the new emerging technologies and delivery systems, efforts are still needed in the right direction to combat this global challenge.


Assuntos
Antibacterianos/administração & dosagem , Antifúngicos/administração & dosagem , Dermatomicoses/tratamento farmacológico , Nanomedicina/métodos , Dermatopatias Bacterianas/tratamento farmacológico , Administração Cutânea , Dermatomicoses/microbiologia , Sistemas de Liberação de Medicamentos/métodos , Humanos , Lipossomos , Nanopartículas Metálicas/química , Nanomedicina/legislação & jurisprudência , Patentes como Assunto , Prata/química , Dermatopatias Bacterianas/microbiologia , Resultado do Tratamento
20.
Int J Biol Macromol ; 115: 1012-1025, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29680503

RESUMO

The current research study intends to explore the combined potential of lipid nanoparticles and chitosan as an optimum therapy for the management of wound infections. Fusidic acid (FA), a steroidal antibiotic employed for treatment of primary and secondary topical infections was encapsulated within the nanoengineered lipid-polymer hybrid nanoparticles (FA-LPHNs). A number of variables like lipid/polymer ratio, lipid, surfactant and chitosan concentration, stirring speed were optimized to get the desired particle size and % entrapment efficiency. The developed carriers were further characterized for particle size, antibacterial activity, cytotoxicity studies in HaCat cell lines, ex vivo permeation studies and skin safety profile. The developed LPHNs offered nanometric size (284.67 ±â€¯5.67 nm), sustained drug release (79.31 ±â€¯0.45%) and enhanced drug permeation (72.09 ±â€¯1.26%). The changes in viability of HaCat cells were insignificant indicating the safety profile of LPHNs. The administration of FA-LPHNs resulted in 5-times and 4-times decrease in its inhibitory concentration against MRSA 33591 and MSSA 25921 respectively, along with antibacterial activity for a longer duration. Further, hydrogel incorporated nanoparticles were found to be topically applicable and compatible with mice skin. The studies indicated the superiority of FA-LPHNs for better management of wounds and associated infections over the conventional marketed product.


Assuntos
Infecções Bacterianas/tratamento farmacológico , Quitosana/química , Ácido Fusídico/química , Ácido Fusídico/farmacologia , Lipídeos/química , Nanopartículas/química , Ferimentos e Lesões/microbiologia , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Quitosana/metabolismo , Quitosana/toxicidade , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Feminino , Humanos , Permeabilidade , Ratos , Segurança , Pele/citologia , Pele/efeitos dos fármacos , Pele/metabolismo , Tensoativos/química
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