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1.
Mol Biol Rep ; 51(1): 746, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874663

RESUMO

BACKGROUND: Human Amniotic Membrane (hAM) is endowed with several biological activities and might be considered an optimal tool in surgical treatment for different ophthalmic pathologies. We pioneered the surgical use of hAM to treat retinal pathologies such as macular holes, tears, and retinal detachments, and to overcome photoreceptor damage in age-related macular degeneration. Although hAM contributed to improved outcomes, the mechanisms of its effects are not yet fully understood. The characterization and explanation of the effects of hAM would allow the adoption of this new natural product in different retinal pathologies, operative contexts, and hAM formulations. At this end, we studied the properties of a hAM extract (hAME) on the ARPE-19 cells. METHODS AND RESULTS: A non-denaturing sonication-based technique was developed to obtain a suitable hAME. Viability, proliferation, apoptosis, oxidative stress, and epithelial-mesenchymal transition (EMT) were studied in hAME-treated ARPE-19 cells. The hAME was able to increase ARPE-19 cell viability even in the presence of oxidative stress (H2O2, TBHP). Moreover, hAME prevented the expression of EMT features, such as EMT-related proteins, fibrotic foci formation, and migration induced by different cytokines. CONCLUSIONS: Our results demonstrate that the hAME retains most of the properties observed in the whole tissue by others. The hAME, other than providing a manageable research tool, could represent a cost-effective and abundant drug to treat retinal pathologies in the future.


Assuntos
Âmnio , Apoptose , Proliferação de Células , Sobrevivência Celular , Estresse Oxidativo , Epitélio Pigmentado da Retina , Humanos , Âmnio/citologia , Âmnio/efeitos dos fármacos , Linhagem Celular , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/citologia , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Extratos de Tecidos/farmacologia
2.
J Water Health ; 20(12): 1673-1687, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36573672

RESUMO

Bacterial contamination of water and food is a grave health concern rendering humans quite vulnerable to disease(s), and proving, at times, fatal too. Exploration of the novel diagnostic tools is, accordingly, highly called for to ensure rapid detection of the pathogenic bacteria, particularly Escherichia coli. The current manuscript, accordingly, reports the use of silane-functionalized glass matrices and antibody-conjugated cadmium telluride (CdTe) quantum dots (QDs) for efficient detection of E. coli. Synthesis of QDs (size: 5.4-6.8 nm) using mercaptopropionic acid (MPA) stabilizer yielded stable photoluminescence (∼62%), corroborating superior fluorescent characteristics. A test sample, when added to antibody-conjugated matrices, followed by antibody-conjugated CdTe-MPA QDs, formed a pathogen-antibody QDs complex. The latter, during confocal microscopy, demonstrated rapid detection of the selectively captured pathogenic bacteria (10 microorganism cells/10 µL) with enhanced sensitivity and specificity. The work, overall, encompasses establishment and design of an innovative detection platform in microbial diagnostics for rapid capturing of pathogens in water and food samples.


Assuntos
Técnicas Biossensoriais , Compostos de Cádmio , Pontos Quânticos , Humanos , Escherichia coli , Telúrio , Bactérias , Água
3.
Pharmacol Res ; 159: 104954, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32492490

RESUMO

Fecal microbiota transplant (FMT) has seen a historic emergence in last decade with its sojourn recently entering into a chequered path, due to a few reports of infection and subsequent mortality. Though FMT has been extensively reported, there is no comprehensive report on the delivery routes available for this non-pharmacological treatment option. Safety, efficacy and cost of FMT not only depend on the quality of contents but also on the delivery route employed. A number of delivery routes are in use for conducting FMT, which include upper gastrointestinal routes (UGI) i.e. nasogastric/nasojejunal tube, endoscopy, oral capsules and lower gastrointestinal routes (LGI) like retention enema, sigmoidoscopy or colonoscopy. Capsules, both conventional as well as colon targeted have been the most commonly used formulations. Surprisingly, the success rates with conventional gastric delivery capsules and colon targeted capsules were found to be quite similar indicating the sufficiency of the inoculum size to withstand the microbial loss in the gastric milieu. Patient compliance, cost effectiveness, comfort of administration, level of invasiveness, patient's hospital admission, risk of aspiration and infections, multiplicity of administration required, recurrence rate are the main factors that seem to influence the choice for route of administration of physicians. The best route for FMT has not been established yet. Extensive studies are required to understand the interplay of route adopted, type of donor, physical nature of sample (fresh or frozen), patient compliance and cost effectiveness to design an approach for the risk free, convenient and cost-effective administration route for FMT.


Assuntos
Cecostomia , Endoscopia do Sistema Digestório , Transplante de Microbiota Fecal , Gastroenteropatias/terapia , Microbioma Gastrointestinal , Animais , Cápsulas , Cecostomia/efeitos adversos , Cecostomia/instrumentação , Disbiose , Endoscopia do Sistema Digestório/efeitos adversos , Endoscopia do Sistema Digestório/instrumentação , Transplante de Microbiota Fecal/efeitos adversos , Transplante de Microbiota Fecal/instrumentação , Gastroenteropatias/microbiologia , Gastroenteropatias/fisiopatologia , Humanos , Resultado do Tratamento
4.
Indian J Microbiol ; 60(4): 420-429, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33012868

RESUMO

Worldwide, millions of individuals have been affected by the prevailing SARS-CoV-2. Therefore, a robust immune system remains indispensable, as an immunocompromised host status has proven to be fatal. In the absence of any specific antiviral drug/vaccine, COVID-19 related drug repurposing along with various other non-pharmacological measures coupled with lockdown have been employed to combat this infection. In this context, a plant based rich fiber diet, which happens to be consumed by a majority of the Indian population, appears to be advantageous, as it replenishes the host gut microbiota with beneficial microbes thereby leading to a symbiotic association conferring various health benefits to the host including enhanced immunity. Further, implementation of the lockdown which has proven to be a good non-pharmacological measure, seems to have resulted in consumption of home cooked healthy diet, thereby enriching the beneficial microflora in the gut, which might have resulted in better prognosis of COVID-19 patients in India in comparison to that observed in the western countries.

5.
Phytother Res ; 32(10): 1950-1956, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29876980

RESUMO

Aim of the study was to evaluate a combination of ginger extract (GE; antioxidant, anti-inflammatory) and Lactobacillus acidophilus (LAB; probiotic), in DMH-DSS-induced inflammation-driven colon cancer, in Wistar rats. Effect of varying GE concentration on growth of LAB was assessed in vitro. Colonic histology and permeability, oxidative stress, serum proinflammatory cytokines, expression of selected genes, gut bacteria, and SCFA determination of gut content was monitored after treatment with agents alone or in combination, postdisease induction. Significant increase in LAB CFU was observed following 48 and 96 hr of incubation with GE; 0.4% w/v GE showed the best results and was used in the cobiotic. Cobiotic administration significantly reversed the DMH-DSS-induced colonic histological alterations. Significant (p < .05) reduction in lipid peroxidation and increase in antioxidant levels (catalase and SOD) was observed in cobiotic group, whereas individual agents did not show any effect. Restoration of colonic permeability, decrease in serum inflammatory burden, and downregulation of COX-2, iNOS, and c-Myc expression on treatment with cobiotic was significantly (p < .05) better than individual agents. Neither LAB nor cobiotic administration produced any change in gut bacteria nor SCFA levels, probably due to loss of LAB viability under adverse gut conditions. Study concludes that presented cobiotic has a promising therapeutic potential, which can be improved by a smartly designed formulation.


Assuntos
Inflamação/tratamento farmacológico , Lactobacillus acidophilus , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Probióticos , Zingiber officinale/química , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Carcinógenos , Neoplasias do Colo/tratamento farmacológico , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo , Interleucina-6/sangue , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangue
6.
Drug Dev Ind Pharm ; 44(10): 1701-1712, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29938544

RESUMO

Tetrahydrocurcumin (THC) also referred to as 'white curcumin', is a stable colorless hydrogenated product of curcumin with superior antioxidant and anti-inflammatory properties. The present study is an attempt to elevate the topical bioavailability of THC, post-incorporation into a nano-carrier system with its final dosage as a hydrogel. Lipid nanoparticles of THC (THC-SLNs) prepared by microemulsification technique were ellipsoidal in shape (revealed in transmission electron microscopy) with a mean particle size of 96.6 nm and zeta potential of -22 mV. Total drug content and entrapment efficiency of THC-SLNs was 94.51% ± 2.15% and 69.56% ± 1.35%, respectively. Differential scanning calorimetry and X-ray diffraction studies confirmed the formation of THC-SLNs. In vitro drug release studies showed the drug release from THC-SLNs gel to follow Higuchi's equation revealing a Fickian diffusion. Ex vivo permeation studies indicated a 17 times (approximately) higher skin permeation of THC-SLNs gel as compared with the free THC gel. Skin irritation, occlusion, and stability studies indicated the formulation to be nonirritating, and stable with a desired occlusivity. Pharmacodynamic evaluation in an excision wound mice model clearly revealed the enhanced anti-inflammatory activity of THC-SLNs gel and was further confirmed using biochemical and histopathological studies. It is noteworthy to report here that THC-SLNs gel showed significantly better (p ≤ 0.001) activity than free THC in gel. As inflammation is innate to all the skin disorders, the developed product opens up new therapeutic avenues for several skin diseases. To the best of our knowledge, this is the first paper elaborating the therapeutic usefulness of white curcumin-loaded lipidic nanoparticles for skin inflammation.


Assuntos
Curcumina/análogos & derivados , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/administração & dosagem , Absorção Cutânea/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Administração Cutânea , Animais , Curcumina/administração & dosagem , Curcumina/farmacocinética , Masculino , Camundongos , Nanopartículas/metabolismo , Técnicas de Cultura de Órgãos , Absorção Cutânea/fisiologia , Suínos , Resultado do Tratamento , Cicatrização/fisiologia
7.
Environ Toxicol ; 31(5): 520-32, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25410024

RESUMO

Sesamol is a phenolic component of sesame seed oil, which has been established as an antioxidant and also possesses potential for hepatoprotection. However, its protective role in carbon tetrachloride (CCl4 ) induced sub-chronic hepatotoxicity has not been studied. Limited oral bioavailability (BA) and rapid elimination (as conjugates) in rats is reported for sesamol. Considering its significant antioxidant potential and compromised BA, we packaged sesamol into solid lipid nanoparticles (S-SLNs) to enhance its hepatoprotective bioactivity. S-SLNs prepared by microemulsification method were nearly spherical in shape with an average particle size of 120.30 nm and their oral administration at 8 mg/kg body weight (BW) showed significantly (p < 0.001) better hepatoprotection than free sesamol (FS) and a well established hepatoprotective antioxidant silymarin [SILY (25 mg/kg BW); p < 0.05) in CCl4 induced sub-chronic liver injury in rats. Evaluations were done in terms of histological changes in the liver tissue, liver injury markers (serum alanine aminotransferase, serum aspartate aminotransferase, and serum lactate dehydrogenase); oxidative stress markers (lipid peroxidation, superoxide dismutase, and reduced glutathione) and proinflammatory response marker (tumor necrosis factor-alpha).


Assuntos
Benzodioxóis/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Nanopartículas/química , Fenóis/farmacologia , Substâncias Protetoras/farmacologia , Administração Oral , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Benzodioxóis/química , Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Glutationa/metabolismo , Hidroliases/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Óleos Voláteis/química , Tamanho da Partícula , Fenóis/química , Substâncias Protetoras/química , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
8.
BMC Complement Altern Med ; 15: 142, 2015 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-25935744

RESUMO

BACKGROUND: Sesamol, a component of sesame seed oil, exhibited significant antioxidant activity in a battery of in vitro and ex vivo tests including lipid peroxidation induced in rat liver homogenates. Latter established its potential for hepatoprotection. However, limited oral bioavailability, fast elimination (as conjugates) and tendency towards gastric irritation/toxicity (especially forestomach of rodents) may limit its usefulness. Presently, we packaged sesamol into solid lipid nanoparticles (S-SLNs) to enhance its biopharmaceutical performance and compared the efficacy with that of free sesamol and silymarin, a well established hepatoprotectant, against carbon tetrachloride induced hepatic injury in rats, post induction. A self recovery group in which no treatment was given was used to observe the self-healing capacity of liver. METHODS: S-SLNs prepared by microemulsification method were administered to rats post-treatment with CCl4 (1 ml/kg body weight (BW) twice weekly for 2 weeks, followed by 1.5 ml/kg BW twice weekly for the subsequent 2 weeks). Liver damage and recovery on treatment was assessed in terms of histopathology, serum injury markers (alanine aminotransferase, aspartate aminotransferase), oxidative stress markers (lipid peroxidation, superoxide dismutase, and reduced glutathione) and a pro-inflammatory response marker (tumor necrosis factor alpha). RESULT: S-SLNs (120.30 nm) at a dose of 8 mg/kg BW showed significantly better hepatoprotection than corresponding dose of free sesamol (FS; p < 0.001). Effects achieved with S-SLNs were comparable with silymarin (SILY), administered at a dose of 25 mg/kg BW. Self recovery group confirmed absence of regenerative capacity of hepatic tissue, post injury. CONCLUSION: Use of lipidic nanocarrier system for sesamol improved its efficiency to control hepatic injury. Enhanced effect is probably due to: a) improved oral bioavailability, b) controlled and prolonged effect of entrapped sesamol and iii) reduction in irritation and toxicity, if any, upon oral administration. S-SLNs may be considered as a therapeutic option for hepatic ailments as effectiveness post induction of liver injury, is demonstrated presently.


Assuntos
Benzodioxóis/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Lipídeos , Nanopartículas , Fenóis/administração & dosagem , Extratos Vegetais/administração & dosagem , Sesamum/química , Alanina Transaminase/sangue , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Aspartato Aminotransferases/sangue , Benzodioxóis/farmacologia , Benzodioxóis/uso terapêutico , Tetracloreto de Carbono , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Fenóis/farmacologia , Fenóis/uso terapêutico , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/farmacologia , Ratos Wistar , Silimarina/farmacologia , Superóxido Dismutase/metabolismo
9.
J Microencapsul ; 32(5): 478-87, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26268954

RESUMO

CONTEXT: Sesamol, a potential antioxidant with marked anticancer potential suffers from issues of extensive tissue distribution and local gastric irritation on oral administration. OBJECTIVE: To develop multiunit gastro-retentive floating beads (S-FBs) for localised and prolonged release of sesamol to treat gastric cancers. MATERIALS AND METHODS: S-FBs prepared using calcium carbonate, sodium alginate and hydroxypropylmethyl cellulose (HPMC) in different proportions, were characterised and evaluated in vivo in N-methyl-N-nitro-N-nitroguanidine-induced gastric cancer in rats. Single oral dose plasma pharmacokinetic study was also performed for free sesamol and S-FBs. RESULTS AND DISCUSSION: Restraining sesamol in floating beads, significantly lowered the release (diffusion controlled) rate, increased t50% (31 times) and reduced its in vivo clearance (>1.5 times). Preclinical evaluation showed S-FBs (10 mg/kg) to be significantly better than free sesamol and better/equivalent to methotrexate (2 mg/kg). CONCLUSION: Most of the natural phytochemical or antioxidants show pretreatment effectiveness. We, however, developed and established S-FBs for sustained curative effect.


Assuntos
Benzodioxóis , Portadores de Fármacos , Neoplasias Experimentais/sangue , Neoplasias Experimentais/tratamento farmacológico , Fenóis , Neoplasias Gástricas/sangue , Neoplasias Gástricas/tratamento farmacológico , Animais , Benzodioxóis/química , Benzodioxóis/farmacocinética , Benzodioxóis/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Masculino , Neoplasias Experimentais/induzido quimicamente , Fenóis/química , Fenóis/farmacocinética , Fenóis/farmacologia , Ratos , Ratos Wistar , Neoplasias Gástricas/induzido quimicamente
10.
AAPS PharmSciTech ; 16(2): 364-74, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25319056

RESUMO

Curcumin has diverse biological activities including antioxidant and anti-inflammatory activity. However, its clinical use for topical application is limited due to its poor aqueous solubility and thus, minimal cutaneous bioavailability. Elastic vesicles (EVs) of curcumin were prepared to improve its cutaneous bioavailability and to use it for topical anti-inflammatory effect. Ex vivo skin permeation and retention studies were performed to check if incorporation of curcumin into EVs could improve its permeation into and retention in the skin. Evaluation of acute and chronic anti-inflammatory effect was done using xylene-induced acute ear edema in mice and cotton pellet-induced chronic inflammation in rats, respectively. A significant improvement in flux (nine times) across murine skin was observed when aqueous dispersion of curcumin (flux - 0.46 ± 0.02 µg/h/cm(2)) was compared with curcumin-loaded EVs (flux - 4.14 ± 0.04 µg/h/cm(2)). Incorporation of these curcumin-loaded EVs into a hydrophilic ointment base resulted in higher skin retention (51.66%) in contrast to free curcumin ointment (1.64%) and a marketed formulation (VICCO® turmeric skin cream). The developed ointment showed an effect similar (p < 0.05) to the marketed diclofenac sodium ointment (Omni-gel®) in suppression of acute inflammation in mouse; a significant inhibition (28.8% versus 3.91% for free curcumin) of cotton pellet-induced chronic inflammation was also observed. Thus, curcumin-loaded EVs incorporated in hydrophilic ointment is a promising topical anti-inflammatory formulation.


Assuntos
Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Curcumina/administração & dosagem , Curcumina/química , Inflamação/tratamento farmacológico , Administração Cutânea , Animais , Disponibilidade Biológica , Química Farmacêutica/métodos , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/química , Diclofenaco/administração & dosagem , Diclofenaco/química , Portadores de Fármacos/química , Edema/tratamento farmacológico , Feminino , Interações Hidrofóbicas e Hidrofílicas , Masculino , Camundongos , Pomadas/administração & dosagem , Pomadas/química , Permeabilidade , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , Absorção Cutânea , Solubilidade
11.
Crit Rev Microbiol ; 40(4): 281-92, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23317462

RESUMO

Emerging drug resistance has forced the scientific community to revisit the observational data documented in the folklore and come up with novel and effective alternatives. Candidates from eukaryotic origin including herbal products and antimicrobial peptides are finding a strategic place in the therapeutic armamentarium against infectious diseases. These agents have recently gained interest owing to their versatile applications. Present review encompasses the use of these alternative strategies in their native or designer form, alone or in conjunction with antibiotics, as possible remedial measures. Further to this, the limitations or the possible concerns associated with these options are also discussed at length.


Assuntos
Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Animais , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Doenças Transmissíveis/tratamento farmacológico , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Plantas Medicinais/química
12.
Mediators Inflamm ; 2014: 715130, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24966470

RESUMO

Alcohol-related disorders are one of the challenging current health problems with medical, social, and economic consequences. Endotoxemia, oxidative stress, and release of a variety of inflammatory molecules are established mediators in alcoholic liver injury (ALD). Probiotics like L. plantarum though were reported to attenuate ALD, their in vivo health benefits are limited by their survival and sustenance in the adverse gut conditions. Therefore, to enhance their in vivo performance, chitosan coated alginate beads entrapping L. plantarum were prepared, characterized, and evaluated for their efficacy against ALD in rats. Following chronic alcohol exposure, rats developed endotoxemia, showed enhanced levels of liver enzyme markers, NF-κB levels, and increased cytokines such as TNF- α and IL12/p40 subunit, and reflected significant histological changes in the intestine and liver. However, cosupplementation with double layered microencapsulated probiotic significantly (P < 0.05) reduced the levels of endotoxemia, serum transaminases, NF-κB, and cytokines complemented with restoration of normal histoarchitecture of the intestine and liver. It is being documented here for the first time that the probiotics have the potential to inhibit IL-12/p40 subunit which is a recently explored potential marker for developing novel therapeutic agents. This study reveals that microencapsulation of probiotics may offer a biopharmacological basis for effective management of ALD.


Assuntos
Biomarcadores/sangue , Lactobacillus plantarum , Hepatopatias Alcoólicas/sangue , Hepatopatias Alcoólicas/imunologia , Probióticos/administração & dosagem , Consumo de Bebidas Alcoólicas , Animais , Ácidos e Sais Biliares/química , Citocinas/sangue , Modelos Animais de Doenças , Composição de Medicamentos , Endotoxemia/metabolismo , Endotoxemia/microbiologia , Feminino , Inflamação , Subunidade p40 da Interleucina-12/sangue , Fígado/efeitos dos fármacos , Microscopia Eletrônica de Varredura , NF-kappa B/sangue , Tamanho da Partícula , Porosidade , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangue
13.
Int J Biol Macromol ; 277(Pt 1): 133984, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39053830

RESUMO

Small interfering RNA (siRNA) holds promise as a therapeutic approach for various diseases, yet challenges persist in achieving efficient delivery, biodistribution, and minimizing off-target effects. Lipidic nanoformulations are being developed to address these hurdles, but the optimal dose for preclinical investigations remains unclear. This systematic review and meta-analysis aims to determine the optimal dose of nanoformulated siRNA and explore factors influencing dose and biodistribution, informing future research in this field. A comprehensive search across four electronic databases identified 25 potential studies, with 15 selected for meta-analysis after screening. Quality assessment was conducted using SYRCLE's risk of bias tool modified for animal studies based on research question. Study found an average siRNA dose of 1.513 ± 0.377 mg/kg with mean downregulation of 65.79 % achieved, with siRNA-LNPs mainly accumulating in the liver. While individual factors showed no significant correlation, a positive association between dose and downregulation was observed, alongside other influencing factors. Extrapolating intravenous doses to potential oral doses, we suggest an initial oral dose range of 1.5 to 8 mg/kg, considering siRNA-LNPs bioavailability. These findings contribute to advancing RNA interference research and encourage further exploration of siRNA-based treatments in personalized medicine.


Assuntos
Lipídeos , Nanopartículas , RNA Interferente Pequeno , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/administração & dosagem , Nanopartículas/química , Humanos , Animais , Lipídeos/química , Regulação para Baixo/efeitos dos fármacos , Distribuição Tecidual , Interferência de RNA , Lipossomos
14.
Int J Pharm ; 654: 123974, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38447777

RESUMO

Sesamol, a lignan, obtained from sesame seeds (Sesamum indicum Linn., Pedaliaciae) has a promising antioxidant, and anti-inflammatory profile. When applied topically, free sesamol rapidly crosses skin layers and gets absorbed in systemic circulation. Its encapsulation into solid lipid nanoparticles not only improved its localised delivery to skin but also resulted in better skin retention, as found in ex-vivo skin retention studies. Free and encapsulated sesamol was compared for antimicrobial and antibiofilm activity against some common skin pathogens and it was found that encapsulation improved the antimicrobial profile by 200%. In vivo evaluation in diabetic open excision wound model suggested that encapsulation of sesamol in SLNs substantially enhanced its wound healing potential when investigated for biophysical, biochemical and histological parameters. It was envisaged that this was achieved via inhibiting bacterial growth and clearing the bacterial biofilm at the wound site, and by regulating oxidative stress in skin tissue.


Assuntos
Anti-Infecciosos , Lipossomos , Nanopartículas , Fenóis , Benzodioxóis/farmacologia , Cicatrização
15.
J Control Release ; 371: 67-84, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38768662

RESUMO

In situ gelling systems represent a burgeoning paradigm in ocular drug administration, addressing intrinsic challenges posed by extant ocular formulations, such as compromised bioavailability and constraints in traversing the corneal barrier. This systematic review endeavours to comprehensively examine the contemporary landscape of research in this domain, focusing on the nuanced capabilities of in situ gelling systems to optimize drug delivery and enhance therapeutic outcomes, without much technological complexity. Employing a meticulous search strategy across diverse databases for publications and patents spanning the years 2015 to 2023 a total of 26 research papers and 14 patents meeting stringent inclusion criteria were identified. Synthesizing the collective insights derived from these investigations, it becomes evident that in situ gelling systems confer an ability to protract the residence time of formulations or active pharmaceutical ingredients (APIs) within the ocular milieu. This sustained presence engenders extended drug release kinetics, thereby fostering improved patient compliance and mitigating the proclivity for side effects attendant to frequent dosing. These salutary effects extend to diminished systemic drug absorption, augmented ocular bioavailability, and the prospect of reduced dosing frequencies, thereby amplifying patient adherence to therapeutic regimens. Intriguingly, the protective attributes of in situ gelling systems extend to the establishment of an ocular surface barrier, thereby abating the susceptibility to infections and inflammatory responses. In summation, this review underscores the auspicious potential of in situ gelling systems as a transformative approach to advancing ocular drug delivery, warranting sustained research endeavours and developmental initiatives for the betterment of global patient outcomes.


Assuntos
Administração Oftálmica , Sistemas de Liberação de Medicamentos , Géis , Humanos , Animais , Disponibilidade Biológica , Olho/metabolismo , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/química , Soluções Oftálmicas/administração & dosagem
16.
J Mater Chem B ; 12(33): 7977-8006, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-38946466

RESUMO

The objective of this review is to provide an up-to-date and all-encompassing account of the recent advancements in the domain of interactive wound dressings. Considering the gap between the achieved and desired clinical outcomes with currently available or under-study wound healing therapies, newer more specific options based on the wound type and healing phase are reviewed. Starting from the comprehensive description of the wound healing process, a detailed classification of wound dressings is presented. Subsequently, we present an elaborate and significant discussion describing interactive (unconventional) wound dressings. Latter includes biopolymer-based, bioactive-containing and biosensor-based smart dressings, which are discussed in separate sections together with their applications and limitations. Moreover, recent (2-5 years) clinical trials, patents on unconventional dressings, marketed products, and other information on advanced wound care designs and techniques are discussed. Subsequently, the future research direction is highlighted, describing peptides, proteins, and human amniotic membranes as potential wound dressings. Finally, we conclude that this field needs further development and offers scope for integrating information on the healing process with newer technologies.


Assuntos
Bandagens , Cicatrização , Humanos , Cicatrização/efeitos dos fármacos , Animais , Materiais Biocompatíveis/química
17.
Chem Phys Lipids ; 259: 105374, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38176612

RESUMO

Soluble alpha-amylases play an important role in the catabolism of polysaccharides. In this work, we show that the malt α -amylase can interact with the lipid membrane and further alter its mechanical properties. Vesicle fluctuation spectroscopy is used for quantitative measurement of the membrane bending rigidity of phosphatidylcholines lipid vesicles from the shape fluctuation based on the whole contour of Giant Unilamellar Vesicles (GUVs). The bending rigidity of the 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine lipid vesicles in water increases significantly with the presence of 0.14 micromolar alpha-amylase (AA) in the exterior solution. It appears that the enzyme present in the external solution interacts with the outer layer of the bilayer membrane, leading to an asymmetry of the solution on either side of the bilayer membrane and altering its elasticity. At AA concentration of 1.5 micromolars and above, changes in the morphology of the GUV membrane are observed. The interaction between AA in the external solution and the external leaflet causes the bilayer membrane to curve spontaneously, leading to the formation of outbuds, giving a positive spontaneous curvature of C0 ≤ 0.05 µm-1 at ≈ 1 mg / ml of the AA concentration. We validate and characterize its concentration-dependent role in stabilizing the membrane curvature. Our findings indicate that the involvement of the enzyme, depending on the concentration, can have a considerable effect on the mechanical characteristics of the membrane.


Assuntos
Bicamadas Lipídicas , alfa-Amilases , Bicamadas Lipídicas/química , Fosfatidilcolinas/química , Lipossomas Unilamelares/química
18.
Chem Biol Interact ; 395: 111009, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38641145

RESUMO

The escalating prevalence of lung diseases underscores the need for innovative therapies. Dysbiosis in human body microbiome has emerged as a significant factor in these diseases, indicating a potential role for synbiotics in restoring microbial equilibrium. However, effective delivery of synbiotics to the target site remains challenging. Here, we aim to explore suitable nanoparticles for encapsulating synbiotics tailored for applications in lung diseases. Nanoencapsulation has emerged as a prominent strategy to address the delivery challenges of synbiotics in this context. Through a comprehensive review, we assess the potential of nanoparticles in facilitating synbiotic delivery and their structural adaptability for this purpose. Our review reveals that nanoparticles such as nanocellulose, starch, and chitosan exhibit high potential for synbiotic encapsulation. These offer flexibility in structure design and synthesis, making them promising candidates for addressing delivery challenges in lung diseases. Furthermore, our analysis highlights that synbiotics, when compared to probiotics alone, demonstrate superior anti-inflammatory, antioxidant, antibacterial and anticancer activities. This review underscores the promising role of nanoparticle-encapsulated synbiotics as a targeted and effective therapeutic approach for lung diseases, contributing valuable insights into the potential of nanomedicine in revolutionizing treatment strategies for respiratory conditions, ultimately paving the way for future advancements in this field.


Assuntos
Pneumopatias , Simbióticos , Humanos , Pneumopatias/tratamento farmacológico , Nanoestruturas/química , Pulmão/efeitos dos fármacos , Pulmão/patologia , Animais , Nanopartículas/química
19.
Discov Nano ; 19(1): 145, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39256285

RESUMO

Breast cancer is one of the leading causes of death among women globally, making its diagnosis and treatment challenging. The use of nanotechnology for cancer diagnosis and treatment is an emerging area of research. To address this issue, multiwalled carbon nanotubes (MWCNTs) were ligand exchanged with butyric acid (BA) to gain hydrophilic character. The successful functionalization was confirmed by FTIR spectroscopy. Surface morphology changes were observed using SEM, while TEM confirmed the structural integrity of the MWCNTs after functionalization. Particle size, zeta potential, and UV spectroscopy were also performed to further characterize the nanoparticles. The breast cancer aptamer specific to Mucin-1 (MUC-1) was then conjugated with the functionalized MWCNTs. These MWCNTs successfully targeted breast cancer cells (MDA-MB-231) as examined by cellular uptake studies and exhibited a reduction in cancer-induced inflammation, as evidenced by gene transcription (qPCR) and protein expression (immunoblotting) levels. Immunoblot and confocal-based immunofluorescence assay (IFA) indicated the ability of CNTs to induce photothermal cell death of MDA-MB-231 cells. Upon imaging, cancer cells were effectively visualized due to the MWCNTs' ability to act as magnetic resonance imaging (MRI) contrast agents. Additionally, MWCNTs demonstrated photothermal capabilities to eliminate bound cancer cells. Collectively, our findings pave the way for developing aptamer-labeled MWCNTs as viable "theranostic alternatives" for breast cancer treatment.

20.
Mol Pharm ; 10(1): 225-35, 2013 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-23237302

RESUMO

A pentacyclic triterpenediol (TPD) from Boswellia serrata has significant cytotoxic and apoptotic potential in a large number of human cancer cell lines. To enhance its anticancer potential, it was successfully formulated into solid lipid nanoparticles (SLNs) by the microemulsion method with 75% drug entrapment efficiency. SEM and TEM studies indicated that TPD-SLNs were regular, solid, and spherical particles in the range of 100-200 nm, and the system indicated that they were more or less stable upon storing up to six months. TPD loaded SLNs showed significantly higher cytotoxic/antitumor potential than the parent drug. TPD-SLNs have 40-60% higher cytotoxic and apoptotic potential than the parent drug in terms of IC(50), extent of apoptosis, DNA damage, and expression of pro-apoptotic proteins like TNF-R1, cytochrome-c, and PARP cleavage in HL-60 cells. Moreover, blank SLNs did not have any cytotoxic effect on the cancer as well as in normal mouse peritoneal macrophages. The in vivo antitumor potential of TPD-SLNs was significantly higher than that of TPD alone in Sarcoma-180 solid tumor bearing mice. Therefore, SLNs of TPD successfully increased the apoptotic and anticancer potential of TPD at comparable doses (both in vitro and in vivo). This work provides new insight into improvising the therapeutic efficacy of TPD by adopting novel delivery strategies such as solid lipid nanoparticles.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/química , Boswellia/química , Lipídeos/administração & dosagem , Nanopartículas/administração & dosagem , Nanopartículas/química , Triterpenos Pentacíclicos/administração & dosagem , Triterpenos Pentacíclicos/química , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Química Farmacêutica/métodos , Citocromos c/metabolismo , Dano ao DNA/efeitos dos fármacos , Emulsões/química , Emulsões/farmacologia , Células HL-60 , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Poli(ADP-Ribose) Polimerases/metabolismo , Sarcoma 180/tratamento farmacológico , Sarcoma 180/metabolismo , Proteína de Domínio de Morte Associada a Receptor de TNF/metabolismo
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