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1.
Sci Rep ; 14(1): 8061, 2024 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580693

RESUMO

The purpose of this study is to compare the relative efficacy and safety of long-acting growth hormone (LAGH) as a growth hormone replacement therapy in prepubertal children with growth hormone deficiency (GHD). We searched the PubMed, Embase, CNKI, and Wanfang databases from inception to July 2023 and identified eleven relevant studies. PEG-LAGH showed better effect on height velocity (mean difference [MD]: - 0.031, 95% credibility interval [CrI]: - 0.278, 0.215) than somatrogon (MD: 0.105, 95% CrI: - 0.419, 0.636), somapacitan (MD: 0.802, 95% CrI: - 0.451, 2.068) and lonapegsomatropin (MD: 1.335, 95% CrI: - 0.3, 2.989) when compared with daily growth hormone (DGH). Furthermore, in terms of height standard deviation score, PEG-LAGH demonstrated better improvement (MD: - 0.15, 95% CrI: - 1.1, 0.66) than somatrogon (MD: - 0.055, 95% CrI: - 1.3, 0.51) and somapacitan (MD: 0.22, 95% CrI: - 0.91, 1.3). PEG-LAGH (risk ratio [RR]: 1.00, 95% CrI: 0.82, 1.2) reduced the risk of adverse events compared with other LAGH (somatrogon, RR: 1.1, 95% CrI: 0.98, 1.2; somapacitan, RR: 1.1, 95% CrI: 0.96, 1.4; lonapegsomatropin, RR, 1.1, 95% CrI: 0.91, 1.3) and was comparable with DGH. This is the first study to indirectly compare the LAGH thorough a network meta-analysis and provide evidence of the optimal efficacy of various LAGH specifically PEG-LAGH and acceptable safety profile in prepubertal children with GHD.


Assuntos
Nanismo Hipofisário , Hormônio do Crescimento Humano , Criança , Humanos , Hormônio do Crescimento/uso terapêutico , Metanálise em Rede , Hormônio do Crescimento Humano/uso terapêutico , Nanismo Hipofisário/tratamento farmacológico , Transtornos do Crescimento/tratamento farmacológico , Terapia de Reposição Hormonal
2.
Curr Drug Targets ; 19(2): 155-169, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28606049

RESUMO

BACKGROUND: Alzheimer's disease (AD) is the most frequent age related neurodegenerative disorder. It represents 70% of all dementia. Millions of people have been affected by AD worldwide. It is a complex illness characterized pathologically by accumulation of protein aggregates of amyloid and neurofibrillary tangles containing hyperphosphorylated neuronal tau protein. AD requires drugs that can circumvent the blood-brain barrier (BBB) which is not a simple physical barrier between blood and brain, but acts as an iron curtain, allowing only selective molecules to enter the brain. Unfortunately, this dynamic barrier restricts transport of drugs to the brain; due to which, currently very few drugs are available for AD treatment. OBJECTIVE: The present review focuses mainly on strategies used for administration of drug to the CNS by-passing BBB for the treatment of AD. RESULTS: Many studies have proved to be effective in overcoming BBB and targeting drugs to CNS by using different strategies. Here we have discussed some of the most important drug permeability and drug targeting approaches. CONCLUSION: In conclusion, concentrating solely in development of drug discovery programs is not enough but it is important to maintain balance between the drug discovery and drug delivery systems that are more specific and effective in targeting CNS of AD patients.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Sistemas de Liberação de Medicamentos , Descoberta de Drogas , Doença de Alzheimer/metabolismo , Animais , Transporte Biológico , Humanos
3.
Curr Drug Metab ; 18(3): 174-185, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28059037

RESUMO

Status epilepticus (SE) is an emergency situation, where immediate and effective treatment is required in least possible time as it is associated with neuronal damage, systemic complications, substantial morbidity and mortality depending on status type, duration, age and etiology. In the past few years, morbidity and mortality rate were improved, probably may be due to aggressive use of anti-epileptic drugs in emergency situations. Present literature gives an overview of the conditions leading to SE and its management guidelines in hospital and out of hospital setting emphasizing on the available drug therapies.


Assuntos
Estado Epiléptico , Animais , Anticonvulsivantes/uso terapêutico , Interações Medicamentosas , Serviço Hospitalar de Emergência , Humanos , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/epidemiologia , Estado Epiléptico/etiologia
4.
Expert Rev Clin Pharmacol ; 9(12): 1533-1546, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27825017

RESUMO

INTRODUCTION: Epilepsy is one of the most common neurological disorders, affecting about 2% of the population worldwide. Lamotrigine (LTG) is a second generation anti-epileptic drug (AED) with broad spectrum of activity, a favourable side-effect profile, simpler dosing than earlier drugs and efficacious in diverse epilepsy syndromes. Areas covered: The present review focuses on pharmacodynamics, pharmacokinetics, clinical efficacy, safety and tolerability of LTG and its effect on cognition, psychiatry, quality of life, women and pregnancy along with effect of enzyme inducing and enzyme inhibiting drugs over LTG and their effect on serum level fluctuations by collecting data from various studies over the years until 2016. Expert commentary: Results from various studies and clinical trials indicate that LTG possessed a favourable profile of anticonvulsant activity and good tolerability as a monotherapy/or add-on therapy in children and adult patients against several types of seizures and syndromes. It has wide clinical dose range with favourable pharmacokinetic properties making it an excellent therapeutic option in epilepsy.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Triazinas/uso terapêutico , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/química , Anticonvulsivantes/farmacocinética , Ensaios Clínicos como Assunto , Humanos , Lamotrigina , Estrutura Molecular , Triazinas/efeitos adversos , Triazinas/química , Triazinas/farmacocinética
5.
Drug Deliv ; 23(9): 3471-3479, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27246872

RESUMO

Natural and plant-based polymers could be used for control release of drugs and also helps in targeting drug to the site of action. The main objective of present work was to check the feasibility of plant-based, namely, mango gum polymeric nanoparticles (NPs) as a carrier for central nervous system (CNS) delivery using model drug donepezil (DZP). The NPs were prepared by modified ionic gelation method and emulsion cross-linking method. Zeta sizer results showed that the diameter of NPs was about 90-130 nm. The polymeric DZP-loaded NPs were almost spherical in shape, as revealed by transmission electron microscopy (TEM). On increasing concentration of NPs suspension from 50 µg/ml to 5000 µg/ml there was no significant increase in % hemolysis. In vivo studies showed that brain targeting was achieved. So on the basis of above results, the extracted water soluble fraction of mango gum is a suitable candidate for brain delivery in the form of nanoformulations.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Ânions/química , Fármacos do Sistema Nervoso Central/administração & dosagem , Fármacos do Sistema Nervoso Central/química , Sistema Nervoso Central/efeitos dos fármacos , Portadores de Fármacos/química , Polímeros/química , Animais , Linhagem Celular Tumoral , Donepezila , Sistemas de Liberação de Medicamentos/métodos , Emulsões/administração & dosagem , Emulsões/química , Géis/administração & dosagem , Géis/química , Humanos , Indanos/administração & dosagem , Indanos/química , Nanopartículas/administração & dosagem , Nanopartículas/química , Tamanho da Partícula , Piperidinas/administração & dosagem , Piperidinas/química , Ratos , Ratos Wistar
6.
Drug Deliv ; 23(2): 619-30, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25005581

RESUMO

Nifedipine is a calcium channel blocker extensively used in the treatment of anginal and hypertension. On oral administration it undergoes extensive first pass metabolism, which outweighs its absorbance through gastrointestinal tract (GIT) and bioavailability of the drug in systemic circulation. As an alternative to oral route transdermal route of drug delivery was developed. In the present investigation, proniosomes are prepared by varying the ratio of span-40, lecithin, aqueous phase and polymer. Formulation containing span-40, lecithin, isopropyl alcohol, 0.1% glycerol (5:5:4) and HPMC (2%) showed smaller vesicle size, high entrapment efficiency. The niosomal formation after hydration and their surface morphology of optimized formulation was studied by Motic and transmission electron microscopy. FTIR and differential scanning calorimetry studies were performed to unravel and understand the solid state properties of the drug and chemical interaction with formulation excipients. The ex-vivo Franz-diffusion studies were carried out in pH 6.8 using rat skin and the results showed better permeability of niosomes with good steady state flux and enhancement ratio suggesting the potential of proniosomal carriers for improved transdermal delivery of nifedipine. Skin irritation studies for 7 days, showed that the drug when formulated as proniosomes to be non-irritant with no erythemia development compared to pure drug. From the bio-distribution studies, the vesicles prepared with hydroxy propyl methyl cellulose with span-40 was found to be ideal batch as the concentration of drug at target site was higher.


Assuntos
Anti-Hipertensivos/administração & dosagem , Bloqueadores dos Canais de Cálcio/administração & dosagem , Lipídeos/química , Nifedipino/administração & dosagem , 2-Propanol/química , Administração Cutânea , Animais , Anti-Hipertensivos/química , Anti-Hipertensivos/farmacocinética , Anti-Hipertensivos/toxicidade , Bloqueadores dos Canais de Cálcio/química , Bloqueadores dos Canais de Cálcio/farmacocinética , Bloqueadores dos Canais de Cálcio/toxicidade , Varredura Diferencial de Calorimetria , Composição de Medicamentos , Estabilidade de Medicamentos , Excipientes/química , Glicerol/química , Hexoses/química , Derivados da Hipromelose/química , Derivados da Hipromelose/farmacocinética , Lecitinas/química , Lipossomos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Nifedipino/química , Nifedipino/toxicidade , Tamanho da Partícula , Ratos , Pele/metabolismo , Absorção Cutânea , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Tecnologia Farmacêutica/métodos
7.
Drug Deliv ; 21(4): 243-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24128089

RESUMO

Nanotechnology has brought a revolution in the field of science, which has subsequently lead to development of novel dosage forms such as niosomes, liposomes and proniosomes. Proniosomes overcome the demerits involved with niosomal and liposomal drug delivery systems. Proniosomes are liquid crystalline compact niosome hybrids which upon hydration form niosomes. They help in reducing physical stability problems involved with niosomes such as leaking, fusion, aggregation and provide convenience in dosing, distribution, transportation and storage showing improved results than conventional niosomes. This review focuses on different aspects of proniosome such as preparation, characterization, drug release, applications, merits, demerits, present scenario in market and future trends.


Assuntos
Sistemas de Liberação de Medicamentos/tendências , Lipossomos/química , Pró-Fármacos/química , Animais , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Humanos , Lipossomos/administração & dosagem , Tamanho da Partícula , Pró-Fármacos/administração & dosagem
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