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1.
AAPS PharmSciTech ; 20(6): 220, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31201588

RESUMO

In this study, poly-(lactic-co-glycolic) acid (PLGA) was conjugated with aspartic acid and was characterized by nuclear magnetic resonance and Fourier transform infrared spectroscopy. Docetaxel-loaded polymeric micelles were prepared, and piperine was tagged. The neuroblastoma cytotoxicity studies revealed a substantially higher cytotoxic potential of the developed system to that of plain docetaxel, which was further corroborated by cellular uptake employing confocal laser scanning microscopy. The hemocompatible system was able to enhance the pharmacokinetic profile in terms of 6.5-fold increment in bioavailability followed by a 3.5 times increase in the retention time in comparison with the plain drug. The single-point brain bioavailability of docetaxel was amplified by 3.3-folds, signifying a better uptake and distribution to brain employing these carriers. The findings are unique as the physically adsorbed piperine was released before the DTX, increasing the propensity of curbing the CYP3A4 enzyme, which plays a vital role in the degradation of docetaxel. Meanwhile, piperine might have compromised the P-gp efflux mechanism, which can be ascribed to the enhanced retention of the drug at the target site. The elevated target site concentrations and extended residence by a biocompatible nanocarrier supplemented with co-delivery of piperine inherit immense promises to deliver this BCS class IV drug more safely and effectively.


Assuntos
Alcaloides/química , Antineoplásicos Fitogênicos/administração & dosagem , Benzodioxóis/química , Docetaxel/administração & dosagem , Micelas , Piperidinas/química , Alcamidas Poli-Insaturadas/química , Animais , Antineoplásicos Fitogênicos/farmacocinética , Disponibilidade Biológica , Encéfalo/metabolismo , Linhagem Celular Tumoral , Docetaxel/farmacocinética , Humanos , Ratos , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier
2.
Int J Pharm ; 530(1-2): 263-278, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28774853

RESUMO

Carbon nanotubes (CNTs), a sub-family of fullerenes, are nanosized seamless cylinders of graphene sheets with enormous drug loading potential. The current studies entail the systematic development of berberine (BRB)-loaded multiwalled carbon nanotubes (MWCNTs) with polysorbate and phospholipid coating for effective management of Alzheimer's Disease (AD). For systematic optimization using design of experiment (DoE), a central composite design (FCCD) was employed and the optimized formulation was choosen using numerical desirability function. Optimized formulation exhibited particle size of 186nm, 68.6% drug adsorption and amount of drug released in 16h (Q16h) of 96%. Degree of carboxylation was observed to be 36%. FTIR and FESEM studies confirmed the coating of polysorbate and phospholipid onto the MWCNTs side walls. Confocal studies ratified the uptake potential of BRB-loaded MWCNT formulations on SH-SY5Y cell lines. In vivo pharmacokinetic studies in rats showed significant improvement in the rate and extent of drug absorption in the plasma and brain tissues, both, vis-a-vis pure drug. Behavioral assessment employing Morris Maze test demonstrated the enhanced performance efficiency of the formed MWCNT complexes. Moreover, the phospholipid-coated and the polysorbate-coated MWCNTs exhibited remarkable recovery in memory performance from 18th to 20th day vis-a-vis other groups. Maintenance of normal biochemical levels in brain tissue demonstrated the potential of these coated MWCNTs in reducing ß-amyloid induced AD. The studies, in a nutshell, demonstrate significant potential of polysorbate/phospholipid coated MWCNTs of BRB in holistic management of AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Berberina/farmacologia , Nanotubos de Carbono/química , Adsorção , Animais , Berberina/farmacocinética , Linhagem Celular , Fulerenos , Humanos , Masculino , Tamanho da Partícula , Ratos , Ratos Wistar
3.
Pharm Pat Anal ; 5(3): 169-81, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27088726

RESUMO

Of late, several biologically active antioxidants from natural products have been investigated by the researchers in order to combat the root cause of carcinogenesis, in other words, oxidative stress. Mangiferin, a therapeutically active C-glucosylated xanthone, is extracted from pulp, peel, seed, bark and leaf of Mangifera indica. These polyphenols of mangiferin exhibit antioxidant properties and tend to decrease the oxygen-free radicals, thereby reducing the DNA damage. Indeed, its capability to modulate several key inflammatory pathways undoubtedly helps in stalling the progression of carcinogenesis. The current review article emphasizes an updated account on the patents published on the chemopreventive action of mangiferin, apoptosis induction made on various cancer cells, along with proposed antioxidative activities and patent mapping of other important therapeutic properties. Considering it as promising polyphenol, this paper would also summarize the diverse molecular targets of mangiferin.


Assuntos
Antineoplásicos , Antioxidantes , Patentes como Assunto , Xantonas , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Humanos , Xantonas/química , Xantonas/isolamento & purificação , Xantonas/farmacologia , Xantonas/uso terapêutico
4.
Colloids Surf B Biointerfaces ; 141: 611-622, 2016 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-26916320

RESUMO

The present studies entail the development of the systematically optimized solid self-nanoemulsifying oily formulations (S-SNEOFs) for enhancing the systemic bioavailability of lopinavir and targeting the same to the sanctuary site, i.e., lymphatic system for complete HIV inhibition. The patient-centric quality target product profile (QTPP) was defined and critical quality attributes (CQAs) earmarked. Risk assessment studies, carried out through failure mode and effect critically analysis (FMECA), helped in identifying the plausible risks or failure modes affecting the quality attributes of the drug product. As per the preliminary studies, viz solubility and phase titration studies, and factor screening studies, Maisine (i.e., lipid), Tween 80 (emulgent), Transcutol HP (i.e., cosolvent) were selected as the critical material attributes (CMAs) of the liquid SNEOFs (L-SNEOFs). D-optimal mixture design was employed for the optimization of aforesaid CMAs and evaluated for in vitro dissolution, globule size, ex vivo permeation studies as the critical quality attributes (CQAs). Optimal composition of CMAs, was embarked through numerical optimization and desirability function, exhibited excellent permeation and drug release characteristics besides possessing globule size in nano range, i.e., 53.16 nm. Further to increase the stability and drug loading, the OPT-L-SNEOFs were then adsorbed onto the porous carrier, i.e., Aeroperl, to prepare the OPT-SNEOF tablets which were finally compressed into the tablet employing MCC as the filler. The performance evaluation through in situ SPIP studies ascribed the significant enhancement in absorptivity parameters of both the SNEOFs vis-à-vis the pure drug. Also, chylomicron flow block SPIP studies revealed lymphatic uptake of lopinavir from the SNEOFs. Overall, in vivo pharmacokinetic studies in rats revealed significant improvement in the rate and extent of oral bioavailability of the SNEOFs compared to the pure drug. These studies further substantiate the intestinal lymphatic transport of lopinavir for the management of the sanctuary site HIV. In a nutshell, the SNEOFs offer a complete and holistic solution for the management of the viral loads in the lymph and blood.


Assuntos
Emulsões/química , Mucosa Intestinal/metabolismo , Lopinavir/farmacocinética , Sistema Linfático/metabolismo , Nanopartículas/química , Administração Oral , Animais , Área Sob a Curva , Disponibilidade Biológica , Liberação Controlada de Fármacos , Emulsificantes/química , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/química , Inibidores da Protease de HIV/farmacocinética , Lopinavir/administração & dosagem , Lopinavir/química , Masculino , Taxa de Depuração Metabólica , Microscopia Eletrônica de Transmissão , Nanopartículas/ultraestrutura , Pomadas/química , Ratos Wistar
5.
AAPS PharmSciTech ; 17(5): 1042-8, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26729535

RESUMO

Carbon nanotubes (CNTs), owing to their inherently unique properties in the domain of biomedical sciences including drug delivery, offer an exciting platform to the researchers. Of late, their applications have also been successfully established. Recently, single-walled CNTs (SWCNTs) have been explored for antibacterial efficacy, but naïve multi-walled CNTs (MWCNTs) still remained unearthed. The present studies endeavor the investigation of the potential of various non-ionic surfactants in solubility enhancement of MWCNTs and their subsequent antibacterial efficacy against Escherichia coli and Staphylococcus aureus. Polysorbates offer more solubility to MWCNTs vis-à-vis the phospholipids. However, the antibacterial effect was found to be less influenced by solubility but significantly determined by the type of surfactant. Transmission electron photomicrographs confirmed significant adhesion of MWCNTs to the bacterial walls only in the presence of unsaturated phospholipids and this was expressed in the form of lowest minimum inhibitory concentration (MIC) values of MWCNTs dispersed with the same. The findings are unique as MWCNTs were found to be active against both Gram-negative and Gram-positive bacteria to a similar extent, though somewhat milder than SWCNTs. However, when dispersed with unsaturated phospholipids, the former offer almost comparable antibacterial effects to that of the latter. The study opens a new research domain to further explore the antibacterial effects of non-functionalized and relatively safer MWCNTs, accentuating the importance of biocomponents like unsaturated phospholipids in this purview.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Nanotubos de Carbono/química , Parede Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Fosfolipídeos/química , Staphylococcus aureus/efeitos dos fármacos , Tensoativos/química
6.
J Chromatogr Sci ; 53(7): 1048-59, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25583970

RESUMO

The current studies entail systematic quality by design (QbD)-based development of a simple, rapid, sensitive and cost-effective stability-indicating method for the estimation of olmesartan medoxomil. Quality target method profile was defined and critical analytical attributes (CAAs) for the reverse-phase liquid chromatography method earmarked. Chromatographic separation accomplished on a C18 column using acetonitrile and water (containing 0.1% orthophosphoric acid, pH 3.5) in 40 : 60 (v/v) as mobile phase at a flow rate of 1.0 mL/min with UV detection at 243 nm. Risk assessment studies and screening studies facilitated comprehensive understanding of the factors affecting CAAs. The mobile phase ratio and flow rate were identified as critical method parameters (CMPs) and were systematically optimized using face-centered cubic design, evaluating for CAAs, namely peak area, retention time, theoretical plates and peak tailing. Statistical modelization was accomplished followed by response surface analysis for comprehending plausible interaction(s) among CMPs. Search for optimum solution was conducted through numerical and graphical optimization for demarcating the design space. Analytical method validation and subsequent forced degradation studies corroborated the method to be highly efficient for routine analysis of drug and its degradation products. The studies successfully demonstrate the utility of QbD approach for developing the highly sensitive liquid chromatographic method with enhanced method performance.


Assuntos
Anti-Hipertensivos/análise , Cromatografia de Fase Reversa/métodos , Olmesartana Medoxomila/análise , Acetonitrilos/química , Cromatografia Líquida de Alta Pressão/economia , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/economia , Estabilidade de Medicamentos , Limite de Detecção , Reprodutibilidade dos Testes
7.
Drug Dev Ind Pharm ; 40(7): 869-78, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23600649

RESUMO

Levodopa is the drug of choice in the treatment of Parkinson's disease but it exhibits low oral bioavailability (30%) and very low brain uptake due to its extensive metabolism by aromatic amino acid decarboxylase in the peripheral circulation. Hence, levodopa is co-administered with carbidopa, a peripheral amino acid decarboxylase inhibitor. In an attempt to improve brain uptake and to avoid degradation of levodopa in peripheral circulation and the use of carbidopa in combination, nose to brain drug delivery of levodopa alone via the olfactory route and the trigeminal nerves has been investigated. Chitosan nanoparticles loaded with levodopa (CNL) were prepared and were incorporated in a thermo-reversible gel prepared using Pluronic PF127 (CNLPgel). The preparation of CNL and CNLPgel was optimized for formulation parameters such as chitosan:TPP ratio, drug load Pluronic concentration to obtain desired particle size of CNL, gelling temperature, gelling time and mucoadhesive strength of CNLPgel. Rheological studies indicated a change in the rheological behavior of plain pluronic gel from Newtonian system at 30 °C to pseudoplastic behavior at 35 °C on incorporation of CNL. In vitro release studies from CNL obeyed Higuchi kinetic model, whereas the drug release from CNLPgel followed the Hixson-Crowell model. In vivo studies indicated a maximum recovery of the drug in brain following intranasal administration of CNL suspension in saline closely followed by the drug dispersed in plain pluronic gel.


Assuntos
Antiparkinsonianos/administração & dosagem , Encéfalo/efeitos dos fármacos , Portadores de Fármacos/química , Levodopa/administração & dosagem , Nanopartículas/química , Mucosa Nasal/metabolismo , Adesividade , Administração Intranasal , Animais , Antiparkinsonianos/farmacocinética , Encéfalo/metabolismo , Química Farmacêutica , Quitosana/química , Liberação Controlada de Fármacos , Géis , Levodopa/farmacocinética , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Poloxâmero/química , Ratos Wistar , Reologia , Temperatura Ambiente
8.
Int J Pharm ; 456(1): 65-72, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23973754

RESUMO

Tretinoin (TRE) is a widely used retinoid for the topical treatment of acne, psoriasis, skin cancer and photoaging. Despite unmatchable efficacy, it is associated with several vexatious side effects like marked skin erythema, peeling and irritation, eventually leading to poor patient compliance. Its photo-instability and high lipophilicity also pose challenges in the development of a suitable topical product. The present study, therefore, aims to develop biocompatible lipid-based nanocarriers of TRE to improve its skin delivery, photostability, biocompatibility and pharmacodynamic efficacy. The TRE-loaded liposomes, ethosomes, solid lipid nanoparticles (SLNs) and nanostructured lipidic carriers (NLCs) were prepared and characterized for micromeritics, surface charge, percent drug efficiency and morphology. Bioadhesive hydrogels of the developed systems were also evaluated for rheological characterization, photostability, ex vivo skin permeation and retention employing porcine skin, and anti-psoriatic activity in mouse tail model. Nanoparticulate carriers (SLNs, NLCs) offered enhanced photostability, skin transport and anti-psoriatic activity vis-à-vis the vesicular carriers (liposomes, ethosomes) and the marketed product. However, all the developed nanocarriers were found to be more biocompatible and effective than the marketed product. These encouraging findings can guide in proper selection of topical carriers among diversity of such available carriers systems.


Assuntos
Fármacos Dermatológicos/administração & dosagem , Portadores de Fármacos/administração & dosagem , Psoríase/tratamento farmacológico , Tretinoína/administração & dosagem , Animais , Fármacos Dermatológicos/química , Fármacos Dermatológicos/efeitos da radiação , Portadores de Fármacos/química , Portadores de Fármacos/efeitos da radiação , Estabilidade de Medicamentos , Etanol/química , Feminino , Técnicas In Vitro , Lipídeos/química , Camundongos , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Absorção Cutânea , Luz Solar , Tretinoína/química , Tretinoína/efeitos da radiação
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