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1.
AAPS PharmSciTech ; 20(8): 323, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31654184

RESUMO

The most common route of the drug administration is oral route despite the fact that most drugs have low oral aqueous solubility and bioavailability especially for BCS class II and class IV drugs. Many methods have been developed in recent years to overcome the poor solubility and oral bioavailability which includes self-emulsifying drug delivery systems (SEDDS) as one of the approaches. Not only for hydrophobic drugs, but also for hydrophilic compounds with low permeability, bioavailability can be enhanced by self nanoemulsifying drug delivery systems. Recently, a lot of focus and attention has been put in the conversion of liquid SEDDS (L-SEDDS) to solid SEDDS (S-SEDDS) to overcome the limitations of liquid formulations related to their physical and chemical stability, portability, accurate dosing, and limited choices of dosage forms. This article aims to review the formulation components used in SEDDS, various approaches used in the conversion of L-SEDDS to S-SEDDS, their applications, merits, and demerits.


Assuntos
Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/métodos , Emulsões/síntese química , Administração Oral , Disponibilidade Biológica , Emulsões/administração & dosagem , Emulsões/farmacocinética , Interações Hidrofóbicas e Hidrofílicas , Permeabilidade , Solubilidade
2.
Bratisl Lek Listy ; 120(10): 789-793, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31663356

RESUMO

AIM: Lipid emulsions are promising with regard to the treatment of toxicity by agents of high lipophilic nature. Our objective is to investigate the efficacy of intralipid 20% and calcium administration at different times when symptoms of cardiac toxicity occur during verapamil infusion. METHOD: 24 adult male Spraque-Dawley rats were randomly divided into 4 different groups, the control group, calcium group, calcium following 20% intralipid group and concomitant 20% intralipid and calcium group. Following monitoring under ketamine anesthesia, all groups were administered 37.5 mg kg-1 h-1 verapamil infusion until a 50% decrease occurred in MAPb. At the end of the infusion, verapamil infusion was decreased down to 15 mg kg-1h-1 and the treatment agents predetermined for the groups were administered concomitantly. RESULTS: There is no statistically significant difference between the administration of 20% intralipid synchronized with calcium or as a pretreatment, but both groups provided a higher survival rate when compared to the other groups. CONCLUSIONS: The administration of calcium alone in verapamil toxicity is not sufficient; when calcium and 20% intralipid are administered together, there is no difference between the administration of lipid and calcium concomitantly and the administration of lipid prior to calcium (Tab. 1, Fig. 2, Ref. 23).


Assuntos
Cálcio/uso terapêutico , Fosfolipídeos/administração & dosagem , Óleo de Soja/administração & dosagem , Verapamil/toxicidade , Animais , Emulsões/administração & dosagem , Emulsões Gordurosas Intravenosas , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
3.
Pharm Nanotechnol ; 7(4): 304-313, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31595848

RESUMO

BACKGROUND: Folic acid is essential in many metabolic processes and DNA synthesis. Nevertheless, folic acid is not stable, pH-sensitive, and deteriorated upon light exposure. OBJECTIVE: This work was aimed to improve folic acid stability within vitamin E-based nanoemulsion. METHODS: The nanoemulsion was prepared with self-nanoemulsification method by mixing vitamin E oil, Tween 20, and PEG 400. A pseudoternary phase diagram was constructed with aqueous titration to determine the optimum ratio for the mixture. The globule size, pH and entrapment efficiency were included in the nanoemulsion characterizations. In addition, the influence of centrifugation, storage, and pH on physical and chemical stabilities of folic acid nanoemulsion was evaluated. RESULTS: Optimum formula was obtained from vitamin E, Tween 20, and PEG 400 with the ratio of 1:11:1, and the folic acid amount was 8 mg. The size of folic acidloaded oil globule was 15.10 ± 1.51 nm, and the nanoemulsion pH was 6.24 ± 0.01. The nanoemulsion system was able to load the folic acid completely. Folic acid in nanoemulsion was stable after 14 days at room temperature, and it was more stable compared to folic acid in solution. In addition, the physical and chemical characteristics of folic acid in nanoemulsion was not affected by the simulated gastric condition. CONCLUSION: Hence, nanoemulsion is a promising strategy to enhance folic acid stability.


Assuntos
Emulsões/química , Ácido Fólico/química , Nanopartículas/química , Vitamina E/química , Administração Oral , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Estabilidade de Medicamentos , Emulsões/administração & dosagem , Ácido Fólico/administração & dosagem , Ácido Fólico/farmacologia , Polietilenoglicóis/química , Polissorbatos/química , Vitamina E/administração & dosagem
4.
Nutr. hosp ; 36(5): 1011-1018, sept.-oct. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-184620

RESUMO

Introducción: la nutrición parenteral domiciliaria (NPD) es una técnica compleja que implica un seguimiento multidisciplinar. Objetivos: análisis descriptivo de todos los pacientes incluidos en el programa de NPD. Métodos: estudio retrospectivo de los pacientes con NPD entre 1985 y 2017 en nuestro centro, un hospital universitario terciario. Resultados: analizamos 61 pacientes (32 hombres, edad media: 51,2 años). La patología de base más frecuente fue la neoplasia (32,8%), siendo el síndrome de intestino corto (SIC) la principal indicación de NPD (70,5%). Recibieron NPD parcial 45 pacientes y total, 16. El tipo de catéter más empleado fue el venoso tunelizado. Veinte pacientes la suspendieron por ingesta oral completa (19 los primeros cinco años), 26 por exitus (18 los primeros cinco años) y 15 la mantienen. La neoplasia fue la causa de muerte más frecuente (46,2%) y en un 15,4%, la hepatopatía asociada a NPD. La duración mediana de la NPD fue de 25 meses (1-394), siendo en 24 pacientes mayor a cinco años (ocho fallecidos, solo uno de causa oncológica no relacionada con la NPD). Un 54% presentaron infecciones de catéter, aislándose Staphylococcus coagulasa negativo en el 55,2%, con una tasa de infección de 1,04 por 1,000 días de cateterización. Conclusiones: la NPD es una estrategia terapéutica útil en el fracaso intestinal. El SIC es la indicación más frecuente en nuestra casuística. La patología de base, como la neoplasia, determinará el pronóstico. La infección por catéter es la complicación más frecuente, por lo que es necesario reforzar la educación sanitaria y la profilaxis antiséptica


Introduction: home parenteral nutrition (NPD) is a complex technique that involves multidisciplinary follow-up. Objectives: descriptive analysis of all patients included in the NPD program. Methods: retrospective study of patients with NPD between 1985 and 2017 in our center, a tertiary university hospital. Results: we analyzed 61 patients (32 men, mean age: 51.2 years). The most common underlying pathology was neoplasia (32.8%), with short bowel syndrome (SIC) being the main indication of NPD (70.5%). Forty-five patients received partial NPD and 16 total. The tunnelled vein catheter was the most common venous access used. 20 patients suspended it for complete oral intake (19 the first 5 years), 26 were deceased (18 the first 5 years) and 15 maintain it. Neoplasia was the most frequent cause of death (46.2%) and in 15.4% liver disease was associated with NPD. The median duration of NPD was 25 months [1-394]; being in 24 patients longer than 5 years (8 dead, only 1 for oncologic cause not related to the NPD). Fifty-four per cent had catheter infections, being isolated 55.2% Staphylococcus coagulase negative, with an infection rate of 1.04 per 1000 days of catheterization. Conclusions: NPD is a useful therapeutic strategy in intestinal failure. The SIC is the most frequent indication in our case study. The underlying pathology, such as neoplasia, will determine the prognosis. Catheter infection is the more frequent complication, so it is necessary to strengthen health education and antiseptic prophylaxis


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Nutrição Parenteral no Domicílio/métodos , Nutrição Parenteral no Domicílio/tendências , Estudos de Coortes , Emulsões/administração & dosagem , Comunicação Acadêmica , Epidemiologia Descritiva , Estudos Retrospectivos , Infecções Relacionadas a Cateter/complicações , Estudos Longitudinais
5.
AAPS PharmSciTech ; 20(7): 297, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444661

RESUMO

Miconazole nitrate (MZ) is a BCS class II antifungal poorly water-soluble drug with limited dissolution properties and gastrointestinal side effects. Self-nanoemulsifying delivery system-based gel of MZ can improve both solubility and oral mucosal absorption with enhanced antifungal activity. The study aims to formulate MZ self-nanoemulsion (MZ-NE) and combine it within hyaluronic acid-based gel. MZ solubility in various oils, surfactants, and cosurfactant used in NE formulations were evaluated. Mixture design was implemented to optimize the levels of NE components as a formulation variable to study their effects on the mean globule size and antifungal inhibition zones. Further, the optimized MZ-NE was loaded into a hyaluronic acid gel base. Rheological behavior of the prepared gel was assessed. Ex vivo permeability of optimized formulation across buccal mucous of sheep and inhibition against Candida albicans were examined. Mixture design was used to optimize the composition of MZ-NE formulation as 22, 67, and 10% for clove oil, Labrasol, and propylene glycol, respectively. The optimized formulation indicated globule size of 113 nm with 29 mm inhibition zone. Pseudoplastic flow with thixotropic behavior was observed, which is desirable for oral gels. The optimized formulation exhibited higher ex vivo skin permeability and enhanced antifungal activity by 1.85 and 2.179, respectively, compared to MZ-SNEDDS, and by 1.52 and 1.72 folds, respectively, compared to marketed gel. Optimized MZ-NE hyaluronic acid-based oral gel demonstrated better antifungal activity, indicating its potential in oral thrush pharmacotherapy.


Assuntos
Antifúngicos/administração & dosagem , Candidíase Bucal/tratamento farmacológico , Química Farmacêutica/métodos , Ácido Hialurônico/administração & dosagem , Miconazol/administração & dosagem , Nanocápsulas/administração & dosagem , Administração Oral , Animais , Antifúngicos/síntese química , Antifúngicos/farmacocinética , Candidíase Bucal/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Emulsões/administração & dosagem , Emulsões/síntese química , Emulsões/farmacocinética , Ácido Hialurônico/síntese química , Ácido Hialurônico/farmacocinética , Hidrogéis/administração & dosagem , Hidrogéis/síntese química , Hidrogéis/farmacocinética , Miconazol/síntese química , Miconazol/farmacocinética , Nanocápsulas/química , Ovinos
6.
Korean J Ophthalmol ; 33(4): 343-352, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31389210

RESUMO

PURPOSE: To evaluate the efficacy and safety of cyclosporine nanoemulsion 0.05% compared to cyclosporine emulsion 0.05% and diquafosol sodium 3%. METHODS: This was a multicenter, randomized, evaluator-masked, active control, parallel, phase IV study. A total of 227 patients were randomly allocated to instill cyclosporine nanoemulsion 0.05% (CN) twice daily, cyclosporine emulsion 0.05% (CE) twice daily, or diquafosol sodium 3% (DQ) six times daily. Non-inferiority of CN was analyzed by primary endpoint (cornea and conjunctival staining scores at week 12). The secondary endpoints were scores of corneal staining, conjunctival staining, tear break-up time, Schirmer test, and Ocular Surface Disease Index at weeks 4 and 12. RESULTS: Primary endpoints showed statistically significant improvements in all groups. Primary endpoints were -6.60 for the CN group, -5.28 for the CE group, and -6.63 for the DQ group (National Eye Institute scale from 0 to 33), verifying the non-inferiority of CN compared to CE (95% confidence interval, -0.15 to 2.80, Δ>-2.88). In intergroup comparison between CN and CE groups, the CN group had significantly more decreased conjunctival staining score at week 12. Intergroup comparison between CN and DQ groups showed consistent statistically significant improvements in TBUT and Schirmer test in the CN group. In the DQ group, TBUT showed late statistically significant improvement at week 12 and Schirmer test showed relatively short-term statistically significant improvement at week 4. CONCLUSIONS: Cyclosporine nanoemulsion 0.05% was equivalently efficient compared to cyclosporine emulsion 0.05% and diquafosol sodium 3%. In addition, CN showed significant improvements in several parameters for treatment of dry eyes.


Assuntos
Ciclosporina/administração & dosagem , Síndromes do Olho Seco/tratamento farmacológico , Polifosfatos/administração & dosagem , Nucleotídeos de Uracila/administração & dosagem , Administração Tópica , Adulto , Relação Dose-Resposta a Droga , Síndromes do Olho Seco/diagnóstico , Emulsões/administração & dosagem , Feminino , Seguimentos , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Nanotecnologia , Estudos Prospectivos , Método Simples-Cego , Lágrimas/metabolismo , Resultado do Tratamento
7.
Lipids Health Dis ; 18(1): 157, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31351498

RESUMO

BACKGROUND: The hypolipidemic effect of phytosterols has been wildely recognized, but its application is limited due to its insolubility in water and low solubility in oil. In this study, ß-sitosterol ester with linoleic acids and ß-sitosterol self-microemulsions were prepared and their hypolipidemic effects on hyperlipidemia mice were studied. METHODS: Firstly, the mice were randomly divided into normal group and model group,they were fed with basic diet and high-fat diet for 70 days respectively. After high-fat model mice was successfully established, the model group was further divided into eight groups: HFD (high-fat diet feeding), SELA-TSO(8 ml/kg, SELA:700 mg/kg), TSO (8 ml/kg), SSSM (8 ml/kg,SS:700 mg/kg), NLSM (8 ml/kg), SSHT-TSO (8 ml/kg, SS: 700 mg/kg) and SS-TSO (8 ml/kg, SS: 700 mg/kg) groups, and treated with ß-sitosterol ester with linoleic acid, ß-sitosterol self-microemulsion, commercial ß-sitosterol health tablets and ß-sitosterol powder for 35 days, respectively, and blank control groups were established. At the end of the treatment period, the blood lipid level, tissues, cholesterol and lipids in feces of mice in each group were investigated. Statistical and analytical data with SPSS 17.0 Software,statistical significance was set at p* < 0.05 and p** < 0.01 levels . RESULTS: The order of lowering blood lipid effect is listed as: SSSM> SELA-TSO > SSHT-TSO > SS-TSO, which shows that ß-sitosterolself-microemulsion have the highest treatment effect among the experimental groups. CONCLUSIONS: In this study, a new formulation of ß-sitosterol was developed, and its hypolipidemic effect was investigated. The results showed that ß-sitosterol self-microemulsion has a good blood lipid lowering effect.


Assuntos
Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , Ácido Linoleico/farmacologia , Sitosteroides/farmacologia , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Emulsões/administração & dosagem , Emulsões/química , Emulsões/farmacologia , Fezes/química , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Hipolipemiantes/administração & dosagem , Hipolipemiantes/química , Ácido Linoleico/administração & dosagem , Ácido Linoleico/química , Lipídeos/sangue , Masculino , Camundongos , Microscopia Eletrônica de Transmissão , Tamanho do Órgão/efeitos dos fármacos , Sitosteroides/administração & dosagem , Sitosteroides/química , Comprimidos/administração & dosagem , Comprimidos/farmacologia
8.
Eur J Pharm Biopharm ; 142: 258-264, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31276759

RESUMO

The effect of drug load and digestion on the solubilization and absorption of fenofibrate in self-nanoemulsifying drug delivery system (SNEDDS) was assessed in a pharmacokinetic study in rats and in an in vitro lipolysis model. SNEDDS containing fenofibrate at 75% of equilibrium solubility (Seq), a super-saturated SNEDDS (super-SNEDDS) containing fenofibrate at 150% of Seq and a super-SNEDDS suspension containing fenofibrate at 100% of Seq and an additional 50% Seq fenofibrate suspended (150% of Seq in total) were used. To assess the effect of lipid digestion on fenofibrate absorption in rats and fenofibrate solubilization during in vitro lipolysis, the lipase inhibitor orlistat was added at 1% (w/w) to the SNEDDS, resulting in six different SNEDDS: SNEDDS, super-SNEDDS and super-SNEDDS suspension with and without orlistat 1% (w/w). In vivo, super-SNEDDS had a higher Cmax and AUC0-30h compared to SNEDDS and super-SNEDDS suspension, both with and without orlistat. While orlistat did not affect fenofibrate absorption in SNEDDS and super-SNEDDS, an increase of Tmax and AUC0-30h for super-SNEDDS suspension was found when orlistat was present. During in vitro lipolysis, the addition of orlistat decreased digestion and lowered drug precipitation. Super-SNEDDS showed significantly increased absorption in rats compared to SNEDDS and super-SNEDDS suspension and the inhibition of digestion resulted in prolonged and increased absorption for the super-SNEDDS suspension.


Assuntos
Fenofibrato/administração & dosagem , Fenofibrato/metabolismo , Administração Oral , Animais , Sistemas de Liberação de Medicamentos/métodos , Emulsões/administração & dosagem , Emulsões/farmacocinética , Absorção Intestinal/efeitos dos fármacos , Lipase/metabolismo , Lipólise/efeitos dos fármacos , Masculino , Nanopartículas/administração & dosagem , Nanopartículas/metabolismo , Ratos , Ratos Sprague-Dawley , Solubilidade/efeitos dos fármacos , Suspensões/administração & dosagem , Suspensões/farmacocinética
9.
Eur J Pharm Sci ; 136: 104956, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31202895

RESUMO

The objective of present study was to develop hydrogel based nanoemulsion (NE) drug delivery system for transdermal delivery and evaluate its potential in in vivo anti-osteoporotic activity. NE was prepared using aqueous phase titration method and characterized for droplet size, zeta potential and morphology. It was then formulated into hydrogel based NE gel using carbopol 940 as gelling agent. NE gel was evaluated for pH, viscosity, in vitro/ex vivo permeation studies and in vivo anti-osteoporotic activity. The results indicated formation of spherical, nano sized globules of NE ranging from 11.17 ±â€¯0.24 to 128.8 ±â€¯0.16 nm with polydispersity of <0.5. In vitro and ex vivo permeation studies showed significantly higher permeation of NE as well as NE gel in comparison to fluvastatin solution indicating that NE gel can effectively penetrate through skin layers. In vivo anti-osteoporotic results demonstrated formation of new bone in trabecular region of osteoporotic rat femurs through micro-CT scanning radiographs. Biomechanical strength testing demonstrated greater load bearing capacity of rat femurs in the treated animals in comparison with the osteoporotic group. Thus, developed NE gel formulation of fluvastatin demonstrated greater potential for transdermal delivery and in the treatment of osteoporosis.


Assuntos
Emulsões/administração & dosagem , Fluvastatina/administração & dosagem , Géis/administração & dosagem , Osteoporose/tratamento farmacológico , Resinas Acrílicas/química , Administração Cutânea , Animais , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Emulsões/química , Fluvastatina/química , Géis/química , Nanopartículas/administração & dosagem , Nanopartículas/química , Nanotecnologia/métodos , Tamanho da Partícula , Ratos , Pele/metabolismo , Absorção Cutânea/efeitos dos fármacos , Viscosidade/efeitos dos fármacos
10.
Biomed Chromatogr ; 33(10): e4615, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31166608

RESUMO

A high-performance liquid chromatography method for temozolomide (TMZ) determination in complex biological matrices was developed and validated for application in in vitro, ex vivo and in vivo studies of new nanotechnology-based systems for TMZ nasal delivery. The method was able to quantify TMZ in nanoemulsions, following cellular uptake, in the porcine nasal mucosa and in mouse plasma and brain. Analyses were performed on a C18 column at 35°C, under UV detection at 330 nm. The mobile phase was methanol-acetic acid 0.5% (30:70, v/v), eluted at an isocratic flow rate of 1.1 mL/min. The method was found to be specific, precise, accurate, robust and linear (0.05 to 5 µg/mL) for TMZ determination in all matrices. No interference of TMZ degradation products was found under various stress conditions such as acidic, alkaline, oxidative, light and thermal exposure, demonstrating stability. The method was applied for the quantification of TMZ in different matrices, i.e. the efficiency of nanoemulsions in vitro in increasing TMZ cellular uptake, ex vivo TMZ permeation and retention in the porcine nasal mucosa tissue, and for in vivo TMZ quantification in mouse brain following intranasal nanoemulsion administration compared with free TMZ.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Temozolomida , Administração Intranasal , Animais , Linhagem Celular Tumoral , Estabilidade de Medicamentos , Emulsões/administração & dosagem , Emulsões/química , Emulsões/farmacocinética , Limite de Detecção , Modelos Lineares , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/administração & dosagem , Nanopartículas/química , Nanopartículas/metabolismo , Reprodutibilidade dos Testes , Espectrofotometria Ultravioleta , Suínos , Temozolomida/administração & dosagem , Temozolomida/análise , Temozolomida/química , Temozolomida/farmacocinética
11.
Eur J Pharm Biopharm ; 142: 92-100, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31176724

RESUMO

HYPOTHESIS: Because of its hydrophilic character the peptide drug Polymyxin B (PMB) cannot be incorporated in lipophilic nanocarrier systems such as self-emulsifying drug delivery systems (SEDDS) for oral administration. Due to the formation of imine conjugates between the primary amino groups of PMB and the carbonyl group of cinnamaldehyde, however, drug lipophilicity might be sufficiently raised for incorporation in SEDDS. METHODS: Imine bonds were formed between the primary amino groups of PMB and the carbonyl group of cinnamaldehyde. PMB-cinnamaldehyde conjugate was characterized regarding degree of substitution, log P and release of PMB due to interaction with bovine serum albumin (BSA), SEDDS loading and cell viability. RESULTS: 87.1% of primary amines formed imines with cinnamaldehyde. Log P was increased 69.183 - folds. BSA triggered release of PMB was 45.2%, 64.9% and 80.6% within 16 h. Log DSEDDS/Release medium of PMB-cinnamaldehyde conjugate was 3.4. CONCLUSION: According to these findings, the concept of imine bond formation with cinnamaldehyde can be considered as a novel concept for increasing lipophilicity of the hydrophilic antibiotic peptide PMB.


Assuntos
Emulsões/química , Iminas/química , Peptídeos/química , Administração Oral , Disponibilidade Biológica , Células CACO-2 , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Emulsificantes/administração & dosagem , Emulsificantes/química , Emulsões/administração & dosagem , Humanos , Interações Hidrofóbicas e Hidrofílicas , Iminas/administração & dosagem , Peptídeos/administração & dosagem , Soroalbumina Bovina/administração & dosagem , Soroalbumina Bovina/química , Solubilidade/efeitos dos fármacos
12.
AAPS PharmSciTech ; 20(5): 201, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31139968

RESUMO

Nanostructured lipid carrier (NLC) of propofol was formulated using hot emulsification-probe sonication method for improvising its parenteral delivery by reducing pain on injection and risk of microbial contamination. The formulated NLC was optimized using central composite design and evaluated for particle size, zeta potential, morphology, free propofol concentration, hemocompatibility, stability, pain on injection, in vivo anesthetic activity, pharmacokinetics, and antimicrobial effectiveness in comparison to the marketed formulation. Optimized NLCs exhibited globule size, less than 200 nm, and zeta potential - 24.1 mV, indicating its stability. TEM images confirmed the spherical shape and nanosize (200 nm) of optimized NLCs. Free propofol concentration was also found to be 40% lesser than marketed formulation. Optimized NLC was found to be non-hemolytic. Rat paw-lick study showed that propofol NLC was significantly less painful compared to the marketed formulation. Anesthetic potential and pharmacokinetics of optimized NLCs were found to be similar to that of the marketed formulation. NLC was found stable in long-term storage under room temperature. Antimicrobial effectiveness study showed that propofol NLC suppressed microbial growth to a greater extent as compared to the marketed formulation. Hence, the developed propofol NLCs appeared to be clinically useful as a potential carrier for propofol delivery.


Assuntos
Emulsões/administração & dosagem , Nanoestruturas/administração & dosagem , Propofol/administração & dosagem , Óleo de Soja/administração & dosagem , Animais , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Emulsões/química , Feminino , Hemólise/efeitos dos fármacos , Hemólise/fisiologia , Humanos , Nanoestruturas/química , Tamanho da Partícula , Propofol/química , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Óleo de Soja/química
13.
Int J Nanomedicine ; 14: 3055-3067, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118622

RESUMO

Purpose: The aim of this research was to develop a phospholipid complex based nanoemulsion system for oral insulin delivery. Methods: Insulin-phospholipid complex (IPC) was firstly prepared by an anhydrous co-solvent lyophilization method, and then encapsulated into the oil phase of nanoemulsion to obtain the IPC-based nanoemulsion (IPC-NE). Both water-in-oil (W/O) IPC-NE and oil-in-water (O/W) IPC-NE were formulated and evaluated for comparison. Results: The obtained W/O IPC-NE and O/W IPC-NE were both spherical in shape with a mean particle size of 18.6±0.79 nm and 27.3±1.25 nm, respectively. While both IPC-NEs exhibited enhanced Caco-2 cell monolayers permeability than IPC and insulin solution, W/O IPC-NE showed relatively greater protective effects against enzymatic degradation than O/W IPC-NE. Moreover, oral administration of W/O IPC-NE exhibited significant hypoglycemic effects, with 12.4-fold and 1.5-fold higher oral bioavailability compared with insulin solution and O/W IPC-NE, respectively. Conclusion: IPC-NEs, especially the W/O IPC-NE showed promising efficiency in vitro and in vivo, thus could be a potential strategy for oral insulin delivery.


Assuntos
Sistemas de Liberação de Medicamentos , Emulsões/química , Insulina/administração & dosagem , Nanopartículas/química , Fosfolipídeos/química , Administração Oral , Animais , Transporte Biológico/efeitos dos fármacos , Glicemia/metabolismo , Células CACO-2 , Morte Celular/efeitos dos fármacos , Portadores de Fármacos , Liberação Controlada de Fármacos , Emulsões/administração & dosagem , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/farmacocinética , Insulina/farmacologia , Masculino , Nanopartículas/ultraestrutura , Tamanho da Partícula , Permeabilidade , Ratos Sprague-Dawley , Suínos , Difração de Raios X
14.
J Pharm Pharmacol ; 71(8): 1199-1208, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31124591

RESUMO

OBJECTIVES: Natural sources with antioxidant activity, such as rosmarinic acid (RA), have been considered as an interesting approach for the development of new anti-ageing skin products. In this context, this study aimed to develop hydrogels containing RA-loaded nanoemulsions and evaluate the effect of the addition of Tween® 80 (a nonionic cosurfactant) in formulations intended to be used for topical application. METHODS: Physico-chemical characterization, in-vitro release and skin retention/permeation from hydrogels of RA-loaded nanoemulsions (containing or not Tween® 80) were evaluated. The RA-loaded nanoemulsion safety profiles were also investigated in keratinocytes (HaCaT cells). KEY FINDINGS: It was observed that all formulations presented adequate physico-chemical characterization for topical application. Furthermore, the results also demonstrated that the presence of Tween® 80 decreased the droplet size and polydispersity index of nanoemulsions and hydrogels. An extended RA release was noted for the hydrogels. However, when comparing the hydrogels, a positive effect of the presence of Tween® 80 on RA retention/permeation in total skin was seen. The RA-loaded nanoemulsion safety profiles demonstrated a good tolerability (3.125-100 µm) in HaCaT cells. CONCLUSIONS: The overall results demonstrated that the formulations developed in this study can be considered as a suitable carrier for RA in a topical application targeting new anti-ageing skin care products.


Assuntos
Cinamatos/administração & dosagem , Cinamatos/química , Depsídeos/administração & dosagem , Depsídeos/química , Emulsões/administração & dosagem , Emulsões/química , Hidrogéis/administração & dosagem , Hidrogéis/química , Nanopartículas/química , Administração Cutânea , Administração Tópica , Animais , Linhagem Celular , Composição de Medicamentos/métodos , Humanos , Nanopartículas/administração & dosagem , Tamanho da Partícula , Polissorbatos/química , Pele/metabolismo , Absorção Cutânea/efeitos dos fármacos , Suínos
15.
Pak J Pharm Sci ; 32(2 (Supplementary)): 845-852, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31103981

RESUMO

Persimmon Fruits (Diospyros kaki L.f, Ebenaceae) and its active principles have long been used in traditional medicines for various cosmetics and skin conditions, however clinical efficacy on various facial skin parameters like roughness, scaliness, hydration, elasticity and wrinkles have not yet been reported. Current study was aimed to analyse polyphenolic constituents of Diospyros kaki fruit extract (DKFE) and to clinically evaluate dermocosmetic emulgels loaded with bioactive phytoconstituents from persimmon fruits, using non-invasive in-vivo evaluation techniques. HPLC analysis established the presence of quercetin, gallic acid, chlorogenic acid, ferulic acid, p-coumeric acid, catechin and cinnamic acid. Results revealed that test formulation produced significant and control showed insignificant (p>0.05) effects on moisture contents and elasticity. Surface evaluation of living skin (SELS) index values were reduced significantly (p<0.05) for the emulgels loaded with DKFE, represented by reduction in skin wrinkles (-12.40%), roughness (-11.76%) and scaliness (-18.59%). Conclusively, a safe and compatible dermocosmetic emulgel formulation loaded with antioxidant enriched DKFE, revealed promising anti-aging attributes that may be due to presence of vital polyphenolic constituents as presented by HPLC analysis.


Assuntos
Envelhecimento/efeitos dos fármacos , Diospyros/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Administração Tópica , Adulto , Antioxidantes/administração & dosagem , Antioxidantes/química , Antioxidantes/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Emulsões/administração & dosagem , Emulsões/química , Emulsões/farmacologia , Flavonoides/análise , Frutas/química , Géis/química , Géis/farmacologia , Humanos , Masculino , Fenóis/análise , Placebos , Extratos Vegetais/administração & dosagem , Pele/química , Pele/efeitos dos fármacos
16.
Drug Dev Ind Pharm ; 45(8): 1265-1276, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30990749

RESUMO

The prevalence of hyperuricemia is relatively high worldwide, and a great number of patients are suffering from its complications. 6-shogaol, an alkylphenol compound purified from the root of ginger (Zingiber officinale Roscoe), has been proved to possess diverse pharmacological activities. However, its poor aqueous solubility usually leads to low bioavailability, and further clinical applications will be greatly discounted. The current study aimed to formulate a 6-shogaol-loaded-Self Microemulsifying Drug Delivery System (SMEDDS) to amend low aqueous solubility and bioavailability orally, as well as, potentiate the hyperuricemic activity of the 6-shogaol. SMEDDS was developed with central composite design established on a two system components viz., 18.62% W/W ethyl oleate (oil phase) and ratio of tween 80 (surfactant) to PEG 400 (co-surfactant) (1.73:1, W/W). Based on quadratic model, the navigation of the design space could generate spherically-shaped and homogenous droplets with respective mean particle diameter, polydispersity and of 20.00 ± 0.26 nm and 0.18 ± 0.02. The 6-shogaol-SMEDDS showed significant elevation of cumulative release compared with the free 6-shogaol and more importantly a 571.18% increment in the relative oral bioavailability of the drug. The predominant accumulation of 6-shogaol-SMEDDS in the liver suggested hepatic-targeting potentiality of the drug. Oral administration of 6-shogaol-SMEDDS in hyperuricemic rats also significantly decreased uric acid level and xanthine oxidase activity. Histological studies confirmed formulation groups indeed could provide better protection of kidney than free drug groups. Collectively, these findings indicated that the SMEDDS hold much promise in enhancing the oral delivery and therapeutic efficacy of 6-shogaol.


Assuntos
Catecóis/administração & dosagem , Catecóis/química , Emulsões/administração & dosagem , Emulsões/química , Hiperuricemia/tratamento farmacológico , Administração Oral , Animais , Disponibilidade Biológica , Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos/métodos , Masculino , Camundongos , Tamanho da Partícula , Polietilenoglicóis/química , Ratos , Ratos Sprague-Dawley , Solubilidade/efeitos dos fármacos , Tensoativos/química
17.
Drug Deliv ; 26(1): 168-178, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30822166

RESUMO

The present study aims at designing a thermosensitive gel prepared from w1/o/w2 multiple microemulsions (MMEs) for the vaginal delivery of siRNA. The w1/o/w2 MMEs were prepared by two-step emulsifications: the first step was to prepare primary emulsions (w1/o) by low energy emulsification (LEE); the second step was to obtain stable w1/o/w2 MMEs by self-emulsifying. An extensive formulation optimization process was undertaken. The final w1/o/w2 MMEs could be formed in ddH2O, phosphate buffer solution (PBS, pH 7.4) and 1640 culture media with diameter size about 166.5 ± 13.1, 271.0 ± 11.1 and 278.7 ± 12.1 nm respectively. The release rates of siRNA from solutions, MMEs and MMEs-gels were completed within 2 h, 6 h and13 h respectively. The transfection efficiency of MMEs was confirmed both in vitro and in vivo. The relative target gene expressions of MMEs were 0.07 ± 0.05% vs. 0.37 ± 0.06% in Hela cells against Lipofectamine2000® and 1.88% ± 0.00% vs. 9.65% ± 0.02% in mouse vaginal mucosa against PEI. Good biocompatibility of MMEs was verified by cytotoxicity and pathological studies. Overall, our results indicated the potential of the MMEs-gel system for the vaginal delivery of siRNA.


Assuntos
Administração Intravaginal , Sistemas de Liberação de Medicamentos/métodos , Emulsões/administração & dosagem , Microesferas , Ácidos Nucleicos/administração & dosagem , Tensoativos/administração & dosagem , Animais , Emulsões/síntese química , Emulsões/metabolismo , Feminino , Géis , Células HeLa , Humanos , Camundongos , Ácidos Nucleicos/síntese química , Ácidos Nucleicos/metabolismo , Distribuição Aleatória , Tensoativos/síntese química , Tensoativos/metabolismo , Água/administração & dosagem , Água/química , Água/metabolismo
18.
Drug Deliv ; 26(1): 147-157, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30822171

RESUMO

Hypoxic pulmonary vasoconstriction (HPV) is a well-characterized vascular response to low oxygen pressures and is involved in life-threatening conditions such as high-altitude pulmonary edema (HAPE) and pulmonary arterial hypertension (PAH). While the efficacy of oral therapies can be affected by drug metabolism, or dose-limiting systemic toxicity, inhaled treatment via pressured metered dose inhalers (pMDI) may be an effective, nontoxic, practical alternative. We hypothesized that a stable water-in-perfluorooctyl bromide (PFOB) emulsion that provides solubility in common pMDI propellants, engineered for intrapulmonary delivery of pulmonary vasodilators, reverses HPV during acute hypoxia (HX). Male Sprague Dawley rats received two 10-min bouts of HX (13% O2) with 20 min of room air and drug application between exposures. Treatment groups: intrapulmonary delivery (PUL) of (1) saline; (2) ambrisentan in saline (0.1 mg/kg); (3) empty emulsion; (4) emulsion encapsulating ambrisentan or sodium nitrite (NaNO2) (0.1 and 0.5 mg/kg each); and intravenous (5) ambrisentan (0.1 mg/kg) or (6) NaNO2 (0.5 mg/kg). Neither PUL of saline or empty emulsion, nor infusions of drugs prevented pulmonary artery pressure (PAP) elevation (32.6 ± 3.2, 31.5 ± 1.2, 29.3 ± 1.8, and 30.2 ± 2.5 mmHg, respectively). In contrast, PUL of aqueous ambrisentan and both drug emulsions reduced PAP by 20-30% during HX, compared to controls. IL6 expression in bronchoalveolar lavage fluid and whole lung 24 h post-PUL did not differ among cohorts. We demonstrate proof-of-concept for delivering pulmonary vasodilators via aerosolized water-in-PFOB emulsion. This concept opens a potentially feasible and effective route of treating pulmonary vascular pathologies via pMDI.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Emulsões/administração & dosagem , Fluorcarbonetos/administração & dosagem , Hipertensão Pulmonar/tratamento farmacológico , Edema Pulmonar/tratamento farmacológico , Água/administração & dosagem , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Emulsões/metabolismo , Fluorcarbonetos/metabolismo , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/metabolismo , Masculino , Fenilpropionatos/administração & dosagem , Fenilpropionatos/metabolismo , Circulação Pulmonar/efeitos dos fármacos , Circulação Pulmonar/fisiologia , Edema Pulmonar/diagnóstico por imagem , Edema Pulmonar/metabolismo , Piridazinas/administração & dosagem , Piridazinas/metabolismo , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento , Água/metabolismo
19.
Mar Drugs ; 17(3)2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30866422

RESUMO

Self-emulsion improves solubility and bioavailability for γ-oryzanol/algae oil, and alginate beads can be used as controlled release carriers. In this study, self-emulsified alginate beads (SEABs) were prepared with different weight ratios of self-emulsion treatment (5%, 10%, 15%, 20%, and 30%) with alginate. We found that the microstructure with a surfactant of SEABs had a different appearance with alginate-based beads. The encapsulation of γ-oryzanol corresponded with the self-emulsion/alginate ratio, which was 98.93~60.20% with a different formulation of SEABs. During in vitro release, SEABs had the gastric protection of γ-oryzanol/algae oil, because γ-oryzanol and emulsion were not released in the simulated stomach fluid. When the SEABs were transferred to a simulation of the small intestine, they quickly began to swell and dissolve, releasing a higher content of the emulsion. We observed that the emulsion that formed had a bimodal distribution in the simulated intestinal fluid as a result of the hydrogel and emulsion droplets, leading to the formation of large aggregates. These results suggested that γ-oryzanol encapsulation within alginate beads via emulsification combined with gelation can serve as an effective controlled delivery system.


Assuntos
Alginatos/química , Fenilpropionatos/química , Alginatos/administração & dosagem , Animais , Disponibilidade Biológica , Preparações de Ação Retardada/química , Composição de Medicamentos , Emulsões/administração & dosagem , Emulsões/química , Suco Gástrico/química , Hidrogéis , Microesferas , Tamanho da Partícula , Fenilpropionatos/administração & dosagem , Pepinos-do-Mar/química , Solubilidade
20.
PLoS One ; 14(1): e0210967, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30677065

RESUMO

This open, prospective, multicenter, observational study was performed to investigate the efficacy and safety of a non-hormonal cream in women undergoing breast cancer treatment and experiencing vulvovaginal dryness symptoms. Overall, 128 patients from 22 study centers participated. The cream was applied to the vagina and vulva for 28 days. For the efficacy analysis, changes in subjective symptoms (feeling of dryness, itching, burning, pain independent of sexual intercourse, dyspareunia, urinary incontinence) were evaluated. Additionally, the following objective diagnostic findings were assessed by a physician: thinning of vaginal epithelium, redness, petechiae, and discharge. Safety and tolerability were assessed by evaluating type and frequency of adverse events, including adverse medical device-related effects. The frequency and intensity of all subjective symptoms significantly improved from baseline at 28 days (p<0.0001). Additionally, 21.4% of patients were completely free of symptoms (p<0.0001) and urinary incontinence was improved or eliminated in 30.8% of women. The overall sum score for all four objective findings was significantly improved from baseline at 28 days (p<0.0001). The frequency of petechial bleedings was significantly reduced (p<0.0001). Further, significant decreases in the severity of vaginal epithelium thinning, redness and petechiae were observed (p<0.0001). More than 88% of patients and investigators assessed the efficacy and tolerability as being good or very good. No serious adverse events were documented. This study demonstrates that the investigated cream is an effective and safe non-hormonal, topical option in the treatment of vulvovaginal dryness symptoms in patients undergoing breast cancer treatment for. However, the study duration and follow-up time of 4 weeks as well as the non-randomized trial design are limitations of the study.


Assuntos
Cremes, Espumas e Géis Vaginais/uso terapêutico , Doenças Vaginais/tratamento farmacológico , Administração Intravaginal , Administração Tópica , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Atrofia , Emulsões/administração & dosagem , Feminino , Humanos , Lubrificantes/administração & dosagem , Menopausa Precoce/efeitos dos fármacos , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Vagina/patologia , Cremes, Espumas e Géis Vaginais/administração & dosagem , Doenças Vaginais/patologia , Doenças Vaginais/fisiopatologia , Vulva/patologia
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