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1.
Exp Parasitol ; 249: 108521, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37011804

RESUMO

In the present study, the larvicidal efficacy of the juices of the weeds Lantana camara Linn (L. camara) and Ocimum gratissimum Linn (O. gratissimum) was evaluated against the larvae of the malaria vectors Aedes aegypti, Anopheles subpictus and Culex quinquefasciatus. The freshly prepared juices of leaves were prepared by grinding them and diluting them at concentrations of 25, 50, 75, and 100 ppm. Twenty larvae of each species were introduced in different sterile Petri dishes in aqueous media under a controlled environment for the assessment of biological activity. The larvicidal activity of both juices was evaluated at 6, 12 and 24 h post-exposure time points by observing the movement of each larva. The obtained data were subjected to probit analysis to determine the lethal concentrations that kill 50% and 90% (LC50 and LC90) of the treated larvae. The results revealed a noticeable larvicidal activity following 24 h of exposure. The juice of L. camara leaves exhibited an LC50 range of 47.47-52.06 ppm and an LC90 range of 104.33-106.70 ppm. Moreover, for the juice of O. gratissimum leaves, the LC50 range was 42.94-44.91 ppm and the LC90 range was 105.11-108.66 ppm. Taken together, the results indicate that the juices of L. camara and O. gratissimum leaves may be useful as effective, economical and eco-friendly larvicidal agents. However, additional studies are needed to explore the bioactive components of the weeds that exhibit larvicidal activity along with their mode of action.


Assuntos
Aedes , Culex , Inseticidas , Lantana , Ocimum , Animais , Mosquitos Vetores , Extratos Vegetais/farmacologia , Inseticidas/farmacologia , Larva , Folhas de Planta
2.
J Immunoassay Immunochem ; 43(1): 1951291, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34355645

RESUMO

The unending outburst of COVID-19 has reinforced the necessity of SARS-CoV-2 identification approaches for the prevention of infection transmission and the proper care of severe and critical patients. As there is no cure, a prompt and reliable diagnosis of SARS-CoV2 is vital to counter the spread and to provide adequate care and treatment for the infection. Currently, RT-PCR is a gold standard detection method for the qualitative and quantitative detection of viral nucleic acids. Besides, enzyme-linked immunosorbent assay is also a primarily used method for qualitative estimation of viral load. However, almost all the detection methods have their pros and cons in terms of specificity, accuracy, sensitivity, cost, time consumption, the need for sophisticated laboratories, and the requirement of skilled technical experts to carry out the detection tests. Thus, it is suggested to integrate different techniques to enhance the detection efficiency and accurateness for SARS-CoV2. This review focuses on preliminary, pre-confirmatory, and confirmatory methods of detection such as imaging techniques (chest-X-ray and chest- computed tomography), nucleic acid detection methods, serological assay methods, and viral culture and identification methods that are currently being employed to detect the presence of SARS-CoV-2 infection along with recent detection method and applicability for COVID-19.


Assuntos
Teste para COVID-19/métodos , COVID-19 , SARS-CoV-2/isolamento & purificação , COVID-19/diagnóstico , Teste de Ácido Nucleico para COVID-19 , Ensaio de Imunoadsorção Enzimática , Humanos , RNA Viral , Radiografia Torácica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Testes Sorológicos , Tomografia Computadorizada por Raios X
3.
Int J Environ Health Res ; 32(8): 1815-1826, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33886400

RESUMO

At the end of 2019 and 2020s, a wave of coronavirus disease 19 (COVID-19) epidemics worldwide has catalyzed a new era of 'communicable infectious diseases'. However, the world is not currently prepared to deal with the growing burden of COVID-19, with the unexpected arrival of Hantavirus infection heading to the next several healthcare emergencies in public. Hantavirus is a significant class of zoonotic pathogens of negative-sense single-stranded ribonucleic acid (RNA). Hemorrhagic renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) are the two major clinical manifestations. Till date, there is no effective treatments or vaccines available, public awareness and precautionary measures can help to reduce the spread of hantavirus disease. In this study, we outline the epidemiology, virology, clinical aspects, and existing HFRS and HCPS management approaches. This review will give an understanding of virus-host interactions and will help for the early preparation and effective handling of further outbreaks in an ever-changing environment.


Assuntos
COVID-19 , Infecções por Hantavirus , Febre Hemorrágica com Síndrome Renal , Orthohantavírus , COVID-19/epidemiologia , Surtos de Doenças , Orthohantavírus/genética , Infecções por Hantavirus/epidemiologia , Febre Hemorrágica com Síndrome Renal/epidemiologia , Humanos
4.
Cell Mol Neurobiol ; 39(2): 181-209, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30671696

RESUMO

Globally, the central nervous system (CNS) disorders appear as the most critical pathological threat with no proper cure. Alzheimer's disease (AD) is one such condition frequently observed with the aged population and sometimes in youth too. Most of the research utilizes different animal models for in vivo study of AD pathophysiology and to investigate the potency of the newly developed therapy. These in vivo models undoubtably provide a powerful investigation tool to study human brain. Although, it sometime fails to mimic the exact environment and responses as the human brain owing to the distinctive genetic and anatomical features of human and rodent brain. In such condition, the in vitro cell model derived from patient specific cell or human cell lines can recapitulate the human brain environment. In addition, the frequent use of animals in research increases the cost of study and creates various ethical issues. Instead, the use of in vitro cellular models along with animal models can enhance the translational values of in vivo models and represent a better and effective mean to investigate the potency of therapeutics. This strategy also limits the excessive use of laboratory animal during the drug development process. Generally, the in vitro cell lines are cultured from AD rat brain endothelial cells, the rodent models, human astrocytes, human brain capillary endothelial cells, patient derived iPSCs (induced pluripotent stem cells) and also from the non-neuronal cells. During the literature review process, we observed that there are very few reviews available which describe the significance and characteristics of in vitro cell lines, for AD investigation. Thus, in the present review article, we have compiled the various in vitro cell lines used in AD investigation including HBMEC, BCECs, SHSY-5Y, hCMEC/D3, PC-2 cell line, bEND3 cells, HEK293, hNPCs, RBE4 cells, SK-N-MC, BMVECs, CALU-3, 7W CHO, iPSCs and cerebral organoids cell lines and different types of culture media such as SCM, EMEM, DMEM/F12, RPMI, EBM and 3D-cell culture.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Desenvolvimento de Medicamentos , Modelos Biológicos , Doença de Alzheimer/genética , Doença de Alzheimer/fisiopatologia , Animais , Técnicas de Cultura de Células , Linhagem Celular , Células Endoteliais/metabolismo , Humanos
5.
Mol Pharm ; 15(10): 4538-4549, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30156844

RESUMO

Currently, there is no treatment strategy which can reverse the process of neuro-degeneration in progression of Alzheimer's disease (AD). Practically, it is desired to achieve and maintain high therapeutic doses in the brain, but it is hard due to selective permeability of the blood-brain barrier (BBB). In the present study, lactoferrin (Lf) was conjugated to polyamidoamine generation 3.0 (PAMAM G3.0) dendrimers for the effective delivery of rivastigmine (RIV) to the brain. Conjugation of PAMAM G3.0 with lactoferrin was confirmed by FT-IR, 1H NMR, and 2D-NMR spectroscopy as well as AFM techniques. Further, RIV was loaded into PAMAM G3.0 and PAMAM-Lf conjugates. RP-HPLC was used to quantify the drug loading and release as well. Spectroscopic analysis confirmed PAMAM-Lf conjugation, the size of the conjugate was 100.04 ± 3.1 nm, and after RIV loading, the size was increased up to 216.13 ± 2.3 nm. Atomic force microscopic results revealed that the root-mean-square roughness ( Rq) and surface roughness ( Ra) were 6.31 and 5.27 nm, respectively, along with other parameters, Skewness and Kurtosis, which were 0.522 and 2.50, respectively. In vitro drug release from the PAMAM-Lf-RIV conjugate was sustained up to more than 100 h, and that of naive RIV was quite rapid (approxmately 99% release was observed in 8 h). Ex vivo hemotoxicity of the PAMAM-Lf-RIV conjugate was almost 9.8-fold lesser than the PAMAM G3.0 ( p < 0.0001), 7.77 times that of PAMAM-enc-RIV and 5 times that of naïve RIV ( p < 0.0001), respectively. The in vivo targeting potency of the conjugate was investigated in a rat model. Bioavailability of the RIV was enhanced 7.87 times compared to RIV along with improved pharmacokinetic parameters. Brain uptake of the drug was improved when treated with PAMAM-Lf-RIV over the RIV and PAMAM-enc-RIV, almost 8 and 4.2 times, respectively, after 4 h of the administration. Additionally, the behavioral studies revealed that PAMAM-Lf-RIV significantly enhanced the overall locomotor activity with higher ambulations over the pure drug and PAMAM-enc-RIV formulation. The outcome of the novel object recognition test was an indirect evidence of memory improvement. Conclusively, the development and characterization of PAMAM-Lf-RIV resulted in improved brain uptake and brain bioavailability with boosted memory, which can be beneficial in the treatment of Alzheimer's.


Assuntos
Encéfalo/metabolismo , Lactoferrina/química , Lactoferrina/farmacologia , Memória/efeitos dos fármacos , Rivastigmina/metabolismo , Rivastigmina/farmacologia , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Cromatografia Líquida de Alta Pressão , Dendrímeros/química , Sistemas de Liberação de Medicamentos/métodos , Masculino , Microscopia de Força Atômica , Ratos , Espectroscopia de Infravermelho com Transformada de Fourier
6.
Mol Pharm ; 14(10): 3356-3369, 2017 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-28836792

RESUMO

Primaquine phosphate (PQ) is mainly used as a radical cure therapy to eradicate relapse of malaria at the liver stage, which is particularly caused by P. falciparum and P. vivax. In the present study, PQ-loaded galactosylated gelatin nanoparticles (Gel-LA-PQ-NPs) were formulated using a one-step desolvation technique. The mean particle size of Gel-LA-PQ-NPs was found to be 93.48 ± 6.36 nm with a zeta potential of 4.80 ± 0.20 mV having 69.90 ± 1.53% encapsulation efficiency. Electron microscopy demonstrated that the NPs were spherical in shape and uniformly distributed without any cluster formation. The in vitro release of PQ from Gel-LA-PQ-NPs has been facilitated in sustained manner, and the release was three times slower than the naïve drug. The prepared nanoparticles (Gel-LA-PQ-NPs) were significantly (p < 0.0001) less hemolytic than the pure drug PQ. The hematological ex vivo study further supported that the developed Gel-LA-PQ-NPs were safer than PQ. The in vitro antiplasmodium assay revealed that the IC50 value against the blood stage of asexual P. falciparum 3D7 strains was significantly (p < 0.01) less (2.862 ± 0.103 µM) for Gel-LA-PQ-NPs than naïve PQ (3.879 ± 0.655 µM). In vivo pharmacokinetic parameters of Gel-LA-PQ-NPs such as half-life and AUC were significantly higher for Gel-LA-PQ-NPs, i.e., with higher bioavailability. Galactosylation of the NPs led to liver targeting of the PQ in animal studies. Approximately eight-fold higher accumulation of PQ was observed in liver compared to pure drug (i.e., PQ). Conclusively, the prepared galactosylated gelatin nanocarrier holds the promising potential and hepatic targetability of an antimalarial, maintaining its safety and biocompatibility.


Assuntos
Antimaláricos/farmacologia , Nanoconjugados/química , Plasmodium falciparum/efeitos dos fármacos , Primaquina/farmacologia , Animais , Antimaláricos/uso terapêutico , Disponibilidade Biológica , Preparações de Ação Retardada/farmacologia , Preparações de Ação Retardada/uso terapêutico , Desenho de Fármacos , Liberação Controlada de Fármacos , Galactose/química , Gelatina/química , Meia-Vida , Hepatócitos/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Tamanho da Partícula , Primaquina/uso terapêutico , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
7.
J Nanosci Nanotechnol ; 15(6): 4070-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26369014

RESUMO

Novel drugs delivery systems (NDDS), formulations from plant actives and extracts are still a matter of thrust and hot cake among the researchers working with phytomedicine. Novel delivery systems such as polymeric liposomes, colloidisomes, aquasomes, ethosomes, niosomes, proliposomes, phytosomes, nanoparticles, nanocapsules, nanoemulsions, microsphere and transferosomes have been proven to be a better carrier for delivery of the phyto-constituents as already done by various eminent scientists. Due to increased bioavailability, protection from toxicity, enhancement of pharmacological activity, enhancement of stability, improved tissue macrophages distribution, sustained delivery, and protection from physical and chemical degradation novel delivery systems are more suitable delivery system in compare to the conventional systems. This articled, highlight the remarkable findings in the recent past by innovators exclusively working on novel drug delivery systems for phyto-constituents.


Assuntos
Lipossomos , Nanomedicina , Nanopartículas , Fitoterapia , Extratos Vegetais , Microesferas , Nanomedicina/métodos , Nanomedicina/tendências , Fitoterapia/métodos , Fitoterapia/tendências
8.
Drug Dev Ind Pharm ; 41(12): 1954-61, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25678314

RESUMO

OBJECTIVE: Although the melphalan (ML) used extensively for the management of breast cancer, its clinical application is limited due to significant hemolytic activity. In the present work, a comparative analysis of two distinct in situ-based thermogelling polymers of PEGylated ML was performed. METHODS: Briefly, the PEGylated conjugate of the melphalan (MLPEG 5000) for local and sustained drug release action is loaded into two different thermogelling polymeric systems, namely chitosan- and poloxamer-based systems. The synthesized conjugate was loaded to a chitosan (MLP 5000) and poloxamer-based (MPX-CG) thermogelling injectable hydrogels. These thermogelling hydrogels were evaluated for in vitro hydrolysis, in vitro hemolytic activity. and in vitro anticancer activity. RESULTS: The lower percent cumulative hydrolysis was witness for both the hydrogels. MPX-CG and MLP 5000 hydrogels as predicted had shown lower percent cumulative hydrolysis of 3.31 ± 0.1 and 1.67 ± 0.1 after 6 h. The percentage hemolysis of MPX-CG and MLP 5000 even at a concentration of 32 µg/ml was found to be 39.23 ± 1.24% and 34.23 ± 2.24%, observed at 1 h, respectively. Both the hydrogels showed similar anticancer pattern, the MPX-CG hydrogel showed low cell viability of 8.4 ± 1.1% at a concentration of 150 µM and the MLP-5000 hydrogel showed slight higher cell viability (13.12 ± 5.4%) as compared with MPX-CG hydrogel. CONCLUSION: Hence, from the present study it can be well understood that both the chitosan- and the poloxamer-based thermogelling hydrogel proves to be an effective drug delivery systems for the delivery of the PEGylated conjugates.


Assuntos
Quitosana/sangue , Sistemas de Liberação de Medicamentos/métodos , Hidrogéis/metabolismo , Melfalan/sangue , Poloxâmero/metabolismo , Polietilenoglicóis/metabolismo , Quitosana/administração & dosagem , Quitosana/química , Relação Dose-Resposta a Droga , Humanos , Hidrogéis/administração & dosagem , Hidrogéis/química , Melfalan/administração & dosagem , Melfalan/química , Poloxâmero/administração & dosagem , Poloxâmero/química , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Temperatura
9.
Biochim Biophys Acta Gen Subj ; 1868(1): 130517, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37935351

RESUMO

BACKGROUND: The mucus biomembrane is a primary barrier in delivering drugs to the brain via intranasal delivery. The negatively charged nanoformulations suffer from poor mucoadhesive ability and less retention time in the nasal cavity, which limits further therapeutic efficacy. The positively charged chitosan coating on liposomes may overcome the above issues. Hence, understanding the molecular interactions between the chitosan-coated liposomes and mucin is essential for developing an effective drug delivery system. METHODS: The molecular interactions of mucin with sinapic acid-loaded liposomes (SA-LPs) and mucin with chitosan-coated sinapic acid-loaded liposomes (SA-CH-LPs) were assessed using different biophysical instrumental analyses by interpreting the UV-Vis spectra and observing the particle size, polydispersity index, surface charge, and rheological behavior. RESULTS: The mucin interaction with SA-CH-LPs showed increased viscosity as compared to SA-LPs with mucin. Moreover, the mucin interaction with SA-CH-LPs showed stronger mucoadhesive properties as compared to SA-LPs with mucin. The electrostatic interaction between positively charged SA-CH-LPs and negatively charged mucin was responsible for the enhanced mucoadhesive property. CONCLUSION: The positively charged SA-CH-LPs highly interact with mucin as compared to negatively charged SA-LPs. The mucoadhesive property of SA-CH-LPs could improve the retention of SA in the nasal cavity as compared to SA-LPs. These findings emphasize the importance of chitosan in modulating the mucoadhesive behavior of liposomes. GENERAL SIGNIFICANCE: Overall, this study helps to understand the molecular interactions and mucoadhesive nature of the chitosan-coated liposomes with mucin, which is essential for biological activity in the physiological environment.


Assuntos
Quitosana , Lipossomos , Mucinas , Lipopolissacarídeos
10.
Int J Biol Macromol ; 271(Pt 2): 132280, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38744364

RESUMO

The successful tissue engineering depends on the development of biologically active scaffolds that possess optimal characteristics to effectively support cellular functions, maintain structural integrity and aid in tissue regeneration. Hydrogels have emerged as promising candidates in tissue regeneration due to their resemblance to the natural extracellular matrix and their ability to support cell survival and proliferation. The integration of hydrogel scaffold into the polymer has a variable impact on the pseudo extracellular environment, fostering cell growth/repair. The modification in size, shape, surface morphology and porosity of hydrogel scaffolds has consequently paved the way for addressing diverse challenges in the tissue engineering process such as tissue architecture, vascularization and simultaneous seeding of multiple cells. The present review provides a comprehensive update on hydrogel production using natural and synthetic biomaterials and their underlying mechanisms. Furthermore, it delves into the application of hydrogel scaffolds in tissue engineering for cardiac tissues, cartilage tissue, adipose tissue, nerve tissue and bone tissue. Besides, the present article also highlights various clinical studies, patents, and the limitations associated with hydrogel-based scaffolds in recent times.


Assuntos
Materiais Biocompatíveis , Hidrogéis , Engenharia Tecidual , Alicerces Teciduais , Hidrogéis/química , Humanos , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Animais , Materiais Biocompatíveis/química , Regeneração/efeitos dos fármacos
11.
Artigo em Inglês | MEDLINE | ID: mdl-38519751

RESUMO

Due to their potential to enhance therapeutic results and enable targeted drug administration, polymer-drug conjugates that use polyethylene glycol (PEG) as both the polymer and the linker for drug conjugation have attracted much research. This study seeks to investigate recent developments in the design and synthesis of PEG-based polymer-drug conjugates, emphasizing fresh ideas that fill in existing knowledge gaps and satisfy the increasing need for more potent drug delivery methods. Through an extensive review of the existing literature, this study identifies key challenges and proposes innovative strategies for future investigations. The paper presents a comprehensive framework for designing and synthesizing PEG-based polymer-drug conjugates, including rational molecular design, linker selection, conjugation methods, and characterization techniques. To further emphasize the importance and adaptability of PEG-based polymer-drug conjugates, prospective applications are highlighted, including cancer treatment, infectious disorders, and chronic ailments.

12.
J Mater Sci Mater Med ; 24(5): 1179-90, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23423649

RESUMO

A novel diclofenac sodium (DS) loaded interpenetrating polymer network (IPN) beads of pectin and hydrolyzed polyacrylamide-graft-sodium alginate (PAAm-g-SA) was developed through ionotropic gelation and covalent cross-linking. The graft copolymer was synthesized by free radical polymerization under the nitrogen atmosphere followed by alkaline hydrolysis. The grafting, alkaline hydrolysis, and characterization of beads were confirmed by Fourier transforms infrared spectroscopy. The crystalline structure of drug after encapsulation into IPN beads were evaluated by differential scanning colorimetry and X-ray diffraction analyses. DS encapsulation was up to 96.45 %. The effect of hydrolyzed graft copolymer/pectin ratios and glutaraldehyde concentration on drug release in acidic and phosphate buffer solutions were investigated. The release of drug was significantly increased with increase of pH. The release of drug depends on the extent of cross-linking. The results indicated that IPN beads of hydrolyzed PAAm-g-SA and pectin could be used for sustained release of DS.


Assuntos
Implantes Absorvíveis , Alginatos/química , Anti-Inflamatórios não Esteroides/administração & dosagem , Diclofenaco/administração & dosagem , Implantes de Medicamento/química , Hidrogel de Polietilenoglicol-Dimetacrilato/síntese química , Pectinas/química , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Materiais Revestidos Biocompatíveis/síntese química , Materiais Revestidos Biocompatíveis/química , Diclofenaco/farmacocinética , Composição de Medicamentos/instrumentação , Sistemas de Liberação de Medicamentos , Implantes de Medicamento/síntese química , Feminino , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Microesferas , Ratos , Ratos Wistar
13.
Drug Dev Ind Pharm ; 39(7): 1053-62, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22779444

RESUMO

Melphalan, a drug used for the treatment of breast, ovaries and a certain type of cancer in the bone marrow, was conjugated to linear methoxy poly (ethylene glycol) (M-PEG) of 2000 and 5000, Da. An ester linkage between polymer and drug was used in the coupling to yield a polymeric prodrug. Purified esters were characterized by Maldi-Tof and IR spectroscopy methods. The modification allowed overcoming the known melphalan aqueous solubility problem (0.1 µg/ml) leading us to obtain a polymer-drug bioconjugate more suitable for oral and parental administration. It was found that molecular weight of M-PEG is critical for the conjugates stability, aqueous solubility (80 times and 123 times higher aqueous solubility for M-PEG 2000 and M-PEG 5000, respectively), and hemolytic activity. The melphalan caused 100% hemolysis above the concentration 3.5 µg/ml in 1 h. whereas conjugate of M-PEG 2000 and M-PEG 5000 shows 81.3 ± 0.5% and 48.8 ± 1.5% hemolysis, respectively at 32 µg/ml after1 h. Further In vitro anticancer activity of melphalan and its conjugates was performed with breast cancer MCF-7 cell lines. It shows that LD50 concentration was higher 1.14 and 2 µm for M-PEG 2000 and M-PEG 5000, respectively in comparison to pure melphalan (0.74 µm). Above studies revealed improved pharmacokinetics properties upon conjugation.


Assuntos
Antineoplásicos Alquilantes/química , Melfalan/química , Polietilenoglicóis/química , Antineoplásicos Alquilantes/farmacologia , Linhagem Celular Tumoral , Cromatografia em Camada Fina , Estabilidade de Medicamentos , Humanos , Hidrólise , Solubilidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectroscopia de Infravermelho com Transformada de Fourier
14.
Saudi Pharm J ; 21(2): 125-41, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23960828

RESUMO

Several methods and techniques are potentially useful for the preparation of microparticles in the field of controlled drug delivery. The type and the size of the microparticles, the entrapment, release characteristics and stability of drug in microparticles in the formulations are dependent on the method used. One of the most common methods of preparing microparticles is the single emulsion technique. Poorly soluble, lipophilic drugs are successfully retained within the microparticles prepared by this method. However, the encapsulation of highly water soluble compounds including protein and peptides presents formidable challenges to the researchers. The successful encapsulation of such compounds requires high drug loading in the microparticles, prevention of protein and peptide degradation by the encapsulation method involved and predictable release, both rate and extent, of the drug compound from the microparticles. The above mentioned problems can be overcome by using the double emulsion technique, alternatively called as multiple emulsion technique. Aiming to achieve this various techniques have been examined to prepare stable formulations utilizing w/o/w, s/o/w, w/o/o, and s/o/o type double emulsion methods. This article reviews the current state of the art in double emulsion based technologies for the preparation of microparticles including the investigation of various classes of substances that are pharmaceutically and biopharmaceutically active.

15.
Colloids Surf B Biointerfaces ; 232: 113613, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37913702

RESUMO

Proteins and peptides (PPs), as therapeutics are widely explored in the past few decades, by virtue of their inherent advantages like high specificity and biocompatibility with minimal side effects. However, owing to their macromolecular size, poor membrane permeability, and high enzymatic susceptibility, the effective delivery of PPs is often challenging. Moreover, their subjection to varying environmental conditions, when administered orally, results in PPs denaturation and structural conformation, thereby lowering their bioavailability. Hence, for effective delivery with enhanced bioavailability, protection of PPs using nanoparticle-based delivery system has gained a growing interest. Mesoporous silica nanoparticles (MSNs), with their tailored morphology and pore size, high surface area, easy surface modification, versatile loading capacity, excellent thermal stability, and good biocompatibility, are eligible candidates for the effective delivery of macromolecules to the target site. This review highlights the different barriers hindering the oral absorption of PPs and the various strategies available to overcome them. In addition, the potential benefits of MSNs, along with their diversifying role in controlling the loading of PPs and their release under the influence of specific stimuli, are also discussed in length. Further, the tuning of MSNs for enhanced gene transfection efficacy is also highlighted. Since extensive research is ongoing in this area, this review is concluded with an emphasis on the potential risks of MSNs that need to be addressed prior to their clinical translation.


Assuntos
Nanopartículas , Dióxido de Silício , Dióxido de Silício/química , Porosidade , Nanopartículas/química , Sistemas de Liberação de Medicamentos/métodos , Peptídeos
16.
J Control Release ; 354: 794-809, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36709923

RESUMO

Understanding and establishing a link between the physicochemical characteristics of nanoparticles (NPs) and their biological interactions poses to be a great challenge in the field of nanotherapeutics. Recent analytical advancements concerning bio-nanointerfaces have accelerated the quest to comprehend the fate of nanocarrier systems in vivo. Scientists have discovered that protein corona, an adsorbed layer of biomolecules on the surface of NPs takes a leading part in interacting with cells and in the cellular uptake process, thereby determining the in vivo behaviour of NPs. Another useful method to assess the in vivo fate of NPs is by performing dissolution testing. This forms the basis for in vitro in vivo correlation (IVIVC), relating in vitro dissolution of NPs and their in vivo properties. Scientists are continuously directing their efforts towards establishing IVIVC for different nanocarrier systems while concurrently gaining insights into protein corona. This review primarily summarizes the importance of protein corona and its interaction with nanoparticles. It also gives an insight into the factors affecting the interaction and various in vitro dissolution media used for varied nanocarrier systems. The article concludes with a discussion of the limitations of IVIVC modelling and its position from a regulatory perspective.


Assuntos
Nanopartículas , Coroa de Proteína , Coroa de Proteína/metabolismo , Nanopartículas/química
17.
Artigo em Inglês | MEDLINE | ID: mdl-37534485

RESUMO

The temperature-triggered in situ gelling system has been revolutionized by introducing an intelligent polymeric system. Temperature-triggered polymer solutions are initially in a sol state and then undergo a phase transition to form a gel at body temperature due to various parameters like pH, temperature, and so on. These smart polymers offer a number of advantages, including ease of administration, long duration of release of the drug, low administration frequency with good patient compliance, and targeted drug delivery with fewer adverse effects. Polymers such as poly(N-isopropylacrylamide) (PNIPAAm), polyethylene glycol (PEG), poly (N, N'-diethyl acrylamide), and polyoxypropylene (PPO) have been briefly discussed. In addition to various novel Drug Delivery Systems (DDS), the smart temperature-triggered polymeric system has various applications in cancer therapy and many other disease conditions. This review focuses on the principals involved in situ gelling systems using various temperature-triggered polymers for chemotherapeutic purposes, using smart DDS, and their advanced application in cancer therapy, as well as available marketed formulations and recent advances in these thermoresponsive sol-gel transforming systems.

18.
Expert Opin Drug Deliv ; 20(12): 1839-1857, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38100459

RESUMO

INTRODUCTION: The efficiency of brain therapeutics is greatly hindered by the blood-brain barrier (BBB). BBB's protective function, selective permeability, and dynamic functionality maintain the harmony between the brain and peripheral region. Thus, the design of any novel drug carrier system requires the complete study and investigation of BBB permeability, efflux transport, and the effect of associated cellular and non-vascular unit trafficking on BBB penetrability. The in vitro BBB models offer a most promising, and reliable mode of initial investigation of BBB permeability and associated factors as strong evidence for further preclinical and clinical investigation. AREA COVERED: This review work covers the structure and functions of BBB components and different types of in vitro BBB models along with factors affecting BBB model development and model selection criteria. EXPERT OPINION: In vivo models assume to reciprocate the physiological environment to the maximum extent. However, the interspecies variability, NVUs trafficking, dynamic behavior of BBB, etc., lead to non-reproducible results. The in vitro models are comparatively less complex, and flexible, as per the study design, could generate substantial evidence and help identify suitable in vivo animal model selection.


Assuntos
Barreira Hematoencefálica , Encéfalo , Animais , Transporte Biológico , Células Endoteliais , Permeabilidade
19.
Biochim Biophys Acta Gen Subj ; 1867(10): 130443, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37573973

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common types of liver cancer; accounts for 75-85% of cases. The treatment and management of HCC involve different sanative options like surgery, chemotherapy, immunotherapy, etc. Recently, various advancements have been introduced for the diagnosis and targeting of hepatic tumor cells. Among these, biomarkers are considered the primary source for the diagnosis and differentiation of tumor cells. With the advancement in the field of nanotechnology, different types of nanocarriers have been witnessed in tumor targeting. Nanocarriers such as nanoparticles, liposomes, polymeric micelles, nanofibers, etc. are readily prepared for effective tumor targeting with minimal side-effects. The emergence of various approaches tends to improve the effectiveness of these nanocarriers as demonstrated in ample clinical trials. This review focuses on the significant role of carbohydrates such as mannose, galactose, fructose, etc. in the development, diagnosis, and therapy of HCC. Hence, the current focus of this review is to acknowledge various perspectives regarding the occurrence, diagnosis, treatment, and management of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Nanotecnologia , Lipossomos , Micelas
20.
J Control Release ; 349: 460-474, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35841998

RESUMO

The unique interfacial properties, huge diversity, and biocompatible nature of phospholipids make them an attractive pharmaceutical excipient. The amphiphilic nature of these molecules offers them the property to self-assemble into distinct structures. The solubility, chemical and structural properties, surface charge, and critical packing parameters of phospholipids play an essential role during formulation design. This review focuses on the relationship between the structural features of a phospholipid molecule and the formation of different lipid-based nanocarrier drug delivery systems. This provides a rationale and guideline for the selection of appropriate phospholipids while designing a drug delivery system. Finally, we refer to relevant recent case studies covering different types of phospholipid-based systems including simple to complex assemblies. Different carriers in the size range of 50 nm to a few microns can be prepared using phospholipids. The carriers can be delivered through oral, intravenous, nasal, dermal, transmucosal, and subcutaneous routes. A wide range of applicability can be achieved by incorporating various hydrophilic and lipophilic additives in the phospholipid bilayer. Advanced research has led to the discovery of phospholipid complexes and cell membrane mimicking lipids. Overall, phospholipids remain a versatile pharmaceutical excipient for drug delivery. They play multiple roles as solubilizer, emulsifier, surfactant, permeation enhancer, coating agent, release modifier, and liposome former.


Assuntos
Lipossomos , Fosfolipídeos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Excipientes , Lipossomos/química , Fosfolipídeos/química , Solubilidade , Tensoativos
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