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1.
Int J Pharm ; 622: 121829, 2022 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-35580686

RESUMO

The oral route is the best way to administer a drug; however, fitting peptide drugs in this route is a major challenge. In insulin cases, less than 0.5% of the administered dose achieves systemic circulation. Oral delivery by nanoparticles can increase insulin permeability across the intestinal epithelium while maintaining its structure and activity until release in the gut. This system can be improved to increase permeability across intestinal cells through active delivery. This study aimed to improve a nanoparticle formulation by promoting functionalization of its surface with immunoglobulin G to increase its absorption by intestinal epithelium. The characterization of formulations showed an adequate size and a good entrapment efficiency. Functionalized nanoparticles led to a desirable increase in insulin release time. Differential scanning calorimetry, infrared spectroscopy and paper chromatography proved the interactions of nanoparticle components. With immunoglobulin G, the nanoparticle size was slightly increased, which did not show aggregate formation. The developed functionalized nanoparticle formulation proved to be adequate to carry insulin and potentially increase its internalization by epithelial gut cells, being a promising alternative to the existing formulations for orally administered low-absorption peptides.


Assuntos
Insulina , Nanopartículas , Administração Oral , Portadores de Fármacos/química , Imunoglobulina G , Nanopartículas/química , Preparações Farmacêuticas , Polímeros/química
2.
Clin Exp Dermatol ; 47(1): 37-42, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34160837

RESUMO

BACKGROUND: Skin conditions have a large emotional, psychological and psychiatric impact on the individual. The All-Party Parliamentary Group on Skin (APPGS) commissioned a qualitative survey to further explore this relationship alongside the experiences of those accessing services in relation to these difficulties in the UK. AIM: To examine the experiences of UK individuals living with a skin condition, and their views of seeking and receiving psychological treatment. This survey formed part of the evidence collected in the preparation of the APPGS Mental Health and Skin Disease report. METHODS: A free-text electronic survey was widely distributed by professional bodies and skin-related charities. Responses were analysed using descriptive thematic analysis and descriptive statistics. Data for each question were classified and labelled, leading to the development of a coding frame. Inter-rater reliability was assessed using Cohen kappa statistic. RESULTS: In total, 544 participants (84% female) completed the survey. The majority of respondents had inflammatory skin diseases such as eczema (43%) or psoriasis (33%). The thematic analysis revealed five key themes associated with impact on mood; impact of intimacy; impact on activities of daily living; lack of recognition from others of the impact; and lack of accessible services. CONCLUSION: The survey demonstrates that there is an urgent need to improve both awareness of the impact that skin conditions can have, and for the provision of psychological services to address this impact.


Assuntos
Acessibilidade aos Serviços de Saúde , Sistemas de Apoio Psicossocial , Dermatopatias/psicologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Autorrelato , Dermatopatias/terapia , Reino Unido
3.
Food Chem ; 339: 127791, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32860997

RESUMO

Monoterpenes are non-polar secondary metabolites widely used by industry due to their excellent therapeutic, food-ingredient and cosmetic properties. However, their low solubility in water limits their use. In this sense, cyclodextrins (CDs) have been widely used to solve these technological challenges. Thus, this study aims to use (-)-borneol as a monoterpene model to prepare inclusion complexes between ß-CD and hydroxypropyl-ß-CD (HP-ß-CD) through different ways and characterize them in order to choose the best inclusion method to improve physicochemical properties of monoterpenes. To achieve this goal, the samples were prepared by physical mixture (PM), paste complex (PA) and freeze-drying complex (FD) and then, extensively characterized by thermal analysis, Fourier-transform infrared spectroscopy, scanning electron microscopy, size particle, X-ray diffraction and nuclear magnetic resonance. The physicochemical results showed that freeze-drying was more effective to form inclusion complexes between (-)-borneol with both CDs. This research highlights the importance of recognizing the best method to prepare inclusion complexes, including food additives as (-)-borneol, to achieve better results in food preparations.


Assuntos
Canfanos/química , beta-Ciclodextrinas/química , 2-Hidroxipropil-beta-Ciclodextrina/química , Varredura Diferencial de Calorimetria , Ingredientes de Alimentos , Liofilização/métodos , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Varredura , Monoterpenos/química , Tamanho da Partícula , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X
5.
Pharm Dev Technol ; 25(9): 1053-1062, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32558594

RESUMO

The aim of this study was to propose the use of spray-dried mucoadhesive carvedilol-loaded nanocapsules in the formulation of sublingual tablets. There is no previous report describing the preparation of tablets containing spray-dried nanocapsules or tablets containing nanocapsules, neither prepared by direct compression nor for sublingual administration. Tablets of 6 mm of diameter and 2.7 ± 0.2 mm of height were obtained with a mean weight of 44 ± 4 mg, carvedilol content of 0.164 ± 0.017 mg, and a disintegration time less than 25 min. They were produced using a force of 4.7 ± 1.6 kgf. The release profile of carvedilol from the tablets was evaluated using the dialysis bag method. In parallel, the release of nanocapsules from the tablet structure into the release medium was evaluated using dynamic light scattering. Nanocapsules that were released from the tablets into the release medium exhibited similar particle size distributions after recovery as in their original liquid suspension, without losing their original ability to control drug release. Therefore, sublingual tablets may be produced from spray-dried drug-loaded nanocapsules using a direct compression technique, providing a useful pharmaceutical approach for drugs that undergo first pass metabolism, such as carvedilol.


Assuntos
Carvedilol/química , Nanocápsulas/química , Comprimidos/química , Administração Sublingual , Química Farmacêutica/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Nanomedicina/métodos , Tamanho da Partícula , Polímeros/química , Suspensões/química
6.
Eur J Pharm Biopharm ; 136: 9-17, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30630060

RESUMO

This paper proposes the development of imiquimod-loaded polymeric nanocapsules formulation for the treatment of cervical cancer. The mechanism of death involved in the reduction of the cell viability as well as the production of an inflammation marker (IL-6) after the treatment in cell line SiHa have been evaluated. The formulation has significantly decreased the viability of the cells in a time-dependent manner, after 24, 48 and 72 h. Additionally, results showed a cellular decrease of almost 80% of the cells after 72 h of treatment. The formulation induced death by apoptosis, necrosis, autophagy, and increased the percentage of SubG1subpopulation of SiHa cells after 72 h. After the same time-interval, the formulation significantly prevented the appearance of colonies, showing effectiveness against SiHa. Finally, the formulation stimulated SiHa cells to release IL-6. These findings open new possibilities for the development of aqueous nanosuspension containing imiquimod as a novel strategy for the treatment of cervical cancer.


Assuntos
Antineoplásicos/administração & dosagem , Citotoxinas/administração & dosagem , Portadores de Fármacos/administração & dosagem , Imiquimode/administração & dosagem , Nanocápsulas/administração & dosagem , Neoplasias do Colo do Útero , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Citotoxinas/metabolismo , Portadores de Fármacos/metabolismo , Feminino , Humanos , Imiquimode/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismo
7.
Biomed Pharmacother ; 94: 10-20, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28750355

RESUMO

Doxazosin has been evaluated for the treatment of several types of cancer. Here, the antitumor effect of the nanoencapsulated form of doxazosin was evaluated in an in vitro model of breast cancer (MCF7 cell line). Doxazosin-loaded polymeric nanocapsules (DXZ-NC) were produced by interfacial deposition of preformed polymer with homogeneous aspect, spherical shape, mean diameter of about 130nm, positive zeta potential (+5mV), and encapsulation efficiency close to 35%. The Alamar Blue® assay and cell counting were carried out to assess cell viability and cell number, respectively. Mechanism of death was evaluated by Annexin/Propidium Iodide staining, while the long-term response was assessed using the clonogenic assay. Nuclear morphometric analysis was investigated using the NMA technique. A significant decrease in cell viability and clonogenicity was observed after the treatment with DXZ-NC when compared to the non-encapsulated drug. All treatments induced apoptosis as the main mechanism of toxicity. In conclusion, the nanoencapsulation of doxazosin improved its in vitro effects in MCF7 cells, without changing the mechanism of cell death underlying its toxicity. This approach was fundamental to reduce the long-term in vitro ability of the remaining tumor cells to form new colonies after the treatment, potentially reducing the risk of tumor recurrence.


Assuntos
Neoplasias da Mama/patologia , Doxazossina/farmacologia , Nanocápsulas/química , Contagem de Células , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Clonais , Liberação Controlada de Fármacos , Feminino , Humanos , Células MCF-7 , Nanocápsulas/ultraestrutura , Tamanho da Partícula
8.
Parasitology ; 144(13): 1769-1774, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28653597

RESUMO

New oral treatments are needed for all forms of leishmaniasis. Here, the improved oral efficacy of quercetin (Qc) and its penta-acetylated derivative (PQc) was evaluated in cutaneous leishmaniasis after encapsulation in lipid-core nanocapsules (LNCs) of poly(ε-caprolactone). Leishmania amazonensis-infected BALB/c mice were given 51 daily oral doses of free drugs (16 mg kg-1) or LNC-loaded drugs (0·4 mg kg-1). While treatment with free Qc reduced the lesion sizes and parasite loads by 38 and 71%, respectively, LNC-Qc produced 64 and 91% reduction, respectively. The antileishmanial efficacy of PQc was similar but not as potently improved by encapsulation as Qc. None of the treatments increased aspartate aminotransferase, alanine aminotransferase or creatinine serum levels. These findings indicate that when encapsulated in LNC, Qc and, to a lesser extent, PQc can safely produce an enhanced antileishmanial effect even at a 40-fold lower dose, with implications for the development of a new oral drug for cutaneous leishmaniasis.


Assuntos
Leishmania mexicana/efeitos dos fármacos , Nanocápsulas , Poliésteres/análise , Quercetina/farmacologia , Tripanossomicidas/farmacologia , Animais , Feminino , Leishmaniose Cutânea/tratamento farmacológico , Lipídeos/análise , Camundongos , Camundongos Endogâmicos BALB C
9.
J Vet Pharmacol Ther ; 40(4): 398-405, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28092108

RESUMO

We investigated the thermal, electrical and mechanical antinociceptive and physiological effects (heart rate, respiratory rate, arterial blood pressure, head height and abdominal auscultation score), and pharmacokinetics, of 0.5 mg/kg of the injectable formulation (ORAL) or nanoparticulated methadone (NANO) given orally, in six adult mares, using a crossover, blind and prospective design. Repeated-measure models were used to compare parametric data between and within treatments, followed by Tukey's test. Nonparametric data were analysed with Wilcoxon signed-rank, adjusted by Bonferroni tests. Blood samples were also collected up to 6 h after dosing for plasma drug quantification by LC-MS/MS. Methadone pharmacokinetic parameters were determined by noncompartmental and compartmental approaches. There were no differences in pharmacodynamic parameters. No statistical differences were observed in the pharmacokinetic parameters from noncompartmental analysis for both groups, except a significant decrease in peak plasma concentration, increase in apparent volume of distribution per fraction absorbed (Vdss /F) and increased mean residence time (MRT) for NANO. One-compartment open model with first order elimination best described the pharmacokinetic profiles for both groups. Neither ORAL nor NANO administered orally to horses produced antinociception. The nanoencapsulated formulation of methadone given orally to horses did not improve methadone pharmacokinetic parameters or increased systemic body exposure to methadone.


Assuntos
Analgésicos Opioides/farmacocinética , Portadores de Fármacos , Cavalos/metabolismo , Metadona/farmacocinética , Administração Oral , Analgésicos Opioides/administração & dosagem , Animais , Estudos Cross-Over , Feminino , Lipídeos , Metadona/administração & dosagem , Estudos Prospectivos , Espectrometria de Massas em Tandem
10.
J Nanosci Nanotechnol ; 16(2): 1310-20, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27433581

RESUMO

An innovative nanocapsule formulation for parenteral administration using selected vegetable oils (mango, jojoba, pequi, oat, annatto, calendula, and chamomile) was developed that has the potential to encapsulate various drugs. The vegetable oil-loaded nanocapsules were prepared by interfacial deposition and compared with capric/caprylic triglyceride-loaded lipid core nanocapsules. The major objective was to investigate the effect of vegetable oils on particle size distribution and physical stability and to determine the hemolytic potential of the nanocapsules, considering their applicability for intravenous administration. Taking into account the importance of accurately determining particle size for the selected route of administration, different size characterization techniques were employed, such as Laser Diffraction, Dynamic Light Scattering, Multiple Light Scattering, Nanoparticle Tracking Analysis, and Transmission Electronic Microscopy. Laser diffraction studies indicated that the mean particle size of all nanocapsules was below 300 nm. For smaller particles, the laser diffraction and multiple light scattering data were in agreement (D[3,2]-130 nm). Dynamic light scattering and nanoparticle tracking analysis, two powerful techniques that complement each other, exhibited size values between 180 and 259 nm for all nanoparticles. Stability studies demonstrated a tendency of particle creaming for jojoba-nanocapsules and sedimentation for the other nanoparticles; however, no size variation occurred over 30 days. The hemolysis test proved the hemocompatibility of all nanosystems, irrespective of the type of oil. Although all developed nanocapsules presented the potential for parenteral administration, jojoba oil-loaded nanocapsules were selected as the most promising nanoformulation due to their low average size and high particle size homogeneity.


Assuntos
Nanocápsulas/química , Óleos de Plantas , Feminino , Humanos , Infusões Parenterais , Masculino , Tamanho da Partícula , Óleos de Plantas/química , Óleos de Plantas/farmacocinética , Óleos de Plantas/farmacologia
11.
Int J Pharm ; 507(1-2): 12-20, 2016 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-27130364

RESUMO

For an improved understanding of the relevant particle features for cutaneous use, we studied the effect of the surface charge of acrylic nanocapsules (around 150nm) and the effect of a chitosan gel vehicle on the particle penetration into normal and stripped human skin ex vivo as well as local tolerability (cytotoxicity and irritancy). Rhodamin-tagged nanocapsules penetrated and remained in the stratum corneum. Penetration of cationic nanocapsules exceeded the penetration of anionic nanocapsules. When applied on stripped skin, however, the fluorescence was also recorded in the viable epidermis and dermis. Cationic surface charge and embedding the particles into chitosan gel favored access to deeper skin. Keratinocytes took up the nanocapsules rapidly. Cytotoxicity (viability<80%), following exposure for ≥24h, appears to be due to the surfactant polysorbate 80, used for nanocapsules stabilization. Uptake by fibroblasts was low and no cytotoxicity was observed. No irritant reactions were detected in the HET-CAM test. In conclusion, the surface charge and chitosan vehicle, as well as the skin barrier integrity, influence the skin penetration of acrylic nanocapsules. Particle localization in the intact stratum corneum of normal skin and good tolerability make the nanocapsules candidates for topical use on the skin, provided that the polymer wall allows the release of the active encapsulated substance.


Assuntos
Quitosana/administração & dosagem , Quitosana/química , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Absorção Cutânea/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Quitosana/efeitos adversos , Quitosana/farmacocinética , Derme/metabolismo , Epiderme/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Géis/administração & dosagem , Géis/efeitos adversos , Géis/química , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Nanocápsulas/efeitos adversos , Tamanho da Partícula , Ácidos Polimetacrílicos/administração & dosagem , Ácidos Polimetacrílicos/efeitos adversos , Ácidos Polimetacrílicos/química , Polissorbatos/administração & dosagem , Polissorbatos/efeitos adversos , Polissorbatos/química , Propriedades de Superfície
12.
J Control Release ; 223: 207-214, 2016 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-26686081

RESUMO

The treatment of various hair disorders has become a central focus of good dermatologic patient care as it affects men and women all over the world. For many inflammatory-based scalp diseases, glucocorticoids are an essential part of treatment, even though they are known to cause systemic as well as local adverse effects when applied topically. Therefore, efficient targeting and avoidance of these side effects are of utmost importance. Optimizing the balance between drug release, interfollicular permeation, and follicular uptake may allow minimizing these adverse events and simultaneously improve drug delivery, given that one succeeds in targeting a sustained release formulation to the hair follicle. To test this hypothesis, three types of polymeric nanocarriers (nanospheres, nanocapsules, lipid-core nanocapsules) for the potent glucocorticoid clobetasol propionate (CP) were prepared. They all exhibited a sustained release of drug, as was desired. The particles were formulated as a dispersion and hydrogel and (partially) labeled with Rhodamin B for quantification purposes. Follicular uptake was investigated using the Differential Stripping method and was found highest for nanocapsules in dispersion after application of massage. Moreover, the active ingredient (CP) as well as the nanocarrier (Rhodamin B labeled polymer) recovered in the hair follicle were measured simultaneously, revealing an equivalent uptake of both. In contrast, only negligible amounts of CP could be detected in the hair follicle when applied as free drug in solution or hydrogel, regardless of any massage. Skin permeation experiments using heat-separated human epidermis mounted in Franz Diffusion cells revealed equivalent reduced transdermal permeability for all nanocarriers in comparison to application of the free drug. Combining these results, nanocapsules formulated as an aqueous dispersion and applied by massage appeare to be a good candidate to maximize follicular targeting and minimize drug penetration into the interfollicular epidermis. We conclude that such nanotechnology-based formulations provide a viable strategy for more efficient drug delivery to the hair follicle. Moreover, they present a way to minimize adverse effects of potent glucocorticoids by releasing the drug in a controlled manner and simultaneously decreasing interfollicular permeation, offering an advantage over conventional formulations for inflammatory-based skin/scalp diseases.


Assuntos
Anti-Inflamatórios/administração & dosagem , Clobetasol/administração & dosagem , Folículo Piloso/metabolismo , Nanocápsulas/administração & dosagem , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Clobetasol/química , Clobetasol/farmacocinética , Liberação Controlada de Fármacos , Humanos , Hidrogéis , Estimulação Física , Poliésteres/química , Suínos
13.
Pharmazie ; 70(3): 155-64, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25980176

RESUMO

The aim of this work was to develop solid lipid nanoparticles (SLN) containing copaiba oil with and without allantoin (NCOA, NCO, respectively) and to evaluate their antifungal activity. Nanoparticle suspensions were prepared using a high homogenisation technique and characterised by dynamic light scattering, laser diffraction, nanoparticle tracking analysis, multiple light scattering analysis, high-pressure liquid chromatography, pH and rheology. The antifungal activities of the formulations were tested in vitro against the emergent yeasts Candida krusei and Candida parapsilosis, and the fungal pathogens of human skin Trichophyton rubrum and Microsporum canis. The dynamic light scattering analysis showed z-average diameters (intensity) between 118.63 ± 8.89 nm for the nanoparticles with both copaiba oil and allantoin and 126.06 ± 9.84nm for the nanoparticles with just copaiba oil. The D[4,3] determined by laser diffraction showed similar results of 123 ± 1.73 nm for the nanoparticles with copaiba oil and allantoin and 130 ± 3.6 nm for the nanoparticles with copaiba oil alone. Nanoparticle tracking analysis demonstrated that both suspensions had monomodal profiles and consequently, the nanoparticle populations were homogeneous. This analysis also corroborated the results of dynamic light scattering and laser diffraction, exhibiting a smaller mean diameter for the nanoparticles with copaiba oil and allantoin (143 nm) than for the nanoparticles with copaiba oil (204 nm). The physicochemical properties indicated that the dispersions were stable overtime. Rheology evidenced Newtonian behaviour for both suspensions. Antifungal susceptibility showed a MIC90 of 125 µg/mL (nanoparticles with copaiba oil) and 7.8 µg/mL (nanoparticles with copaiba oil and allantoin) against C. parapsilosis. The nanoparticles with copaiba oil and the nanoparticles with copaiba oil and allantoin presented a MIC90 of 500 µg/mL and 250 µg/mL, respectively, against C. krusei. The MIC90 values were 500 µg/mL (nanoparticles with copaiba oil) and 1.95 µg/mL (nanoparticles with copaiba oil and allantoin) against T. rubrum. Against M. canis, the nanoparticles with copaiba oil and allantoin had a MIC9 of 1.95 µg/mL. In conclusion, nanoencapsulation improved the antifungal activity of copaiba oil, which was enhanced by the presence of allantoin. The MICs obtained are comparable to those of commercial products and can represent promising therapeutics for cutaneous infections caused by yeasts and dermatophytes.


Assuntos
Alantoína/química , Alantoína/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Composição de Medicamentos/métodos , Fabaceae/química , Lipídeos/química , Nanopartículas/química , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Alantoína/administração & dosagem , Antifúngicos/administração & dosagem , Química Farmacêutica , Fungos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Óleos de Plantas/administração & dosagem , Reologia
14.
Photochem Photobiol Sci ; 13(9): 1253-60, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24977261

RESUMO

The oxidizing capacity and skin penetration of a commercial nanosized ZnO, Nanosun™ (Micronisers-Australia), were evaluated in vitro using porcine skin. Nanosun™ was initially characterized regarding its photo-reactivity and size distribution. An assay using methylene blue was performed to confirm the Nanosun™ photo-reactivity by exposing the labile molecule to UVA irradiation in the presence and absence of the nanosized ZnO. The nanosized ZnO was photo-reactive, reducing the methylene blue concentration to 7% while its concentration remained constant in the control formulation (without ZnO). The product label states that the average particle size is 30 nm. X-ray diffraction, nitrogen sorption and UV-spectrophotometry confirmed the presence of nanometric particles of approximately 30 nm. On the other hand, laser diffractometry showed micrometric particles in the size distribution profile. These analyses indicated that the nanoparticles are arranged as agglomerates and aggregates of micrometric proportions ranging from 0.6 to 60 µm. The skin lipid peroxidation was determined by the formation of thiobarbituric acid reactive species (TBARS) and quantified by UV-spectrophotometry. When exposed to UVA radiation the nanosized ZnO applied porcine skin showed a lower production of TBARS (7.2 ± 1.5 nmol g(-1)) than the controls, the MCT applied porcine skin (18.4 ± 2.8 nmol g(-1)) and the blank porcine skin (14.0 ± 2.0 nmol g(-1)). The penetration of ZnO nanoparticles was studied by scanning electron microscopy and energy dispersive X-ray spectroscopy. The tested ZnO particles did not penetrate into viable layers of the intact porcine skin. The particles tend to accumulate on the skin folds and in these regions they may penetrate into the horny layer.


Assuntos
Óxido de Zinco/química , Animais , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Azul de Metileno/química , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Espectrometria por Raios X , Suínos , Raios Ultravioleta
15.
J Biomed Nanotechnol ; 10(8): 1599-609, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25016659

RESUMO

Tacrolimus is widely used in the prophylaxis of solid-organ transplant rejection. Several studies have reported that tacrolimus has variable and poor bioavailability after oral administration, apart from adverse effects such as gastrointestinal disorders, hyperglycemia, nephro- and neurotoxicity. The aim of this work was to encapsulate tacrolimus (TAC) in lipid-core nanocapsules (LNC) as an oral strategy to deliver the drug. To validate our hypothesis, the pharmacodynamic effect of TAC-LNC was determined after oral and intraperitoneal (i.p.) administrations to mice. TAC-LNC had z-average diameter of 210 nm (unimodal), and 99.5% of encapsulation efficiency. In vitro sustained release was determined for TAC-LNC fitting an anomalous transport mechanism (n = 0.8). TAC-LNC demonstrated higher immunosuppressive activity after oral and i.p. administrations, when compared to the drug solution. TAC-LNC administered at 6.0 mg kg(-1) day(-1) showed equivalent percent reduction in lymphocyte when both routes of administration were used. After oral administration, drug nanoencapsulation allows reducing the dose by at least 40%. Furthermore, the nanoencapsulation of TAC in lipid-core nanocapsules showed pharmacodynamic effect similar for the oral and the i.p. routes. In conclusion, the lipid-core nanocapsules were able to improve the TAC deliver across the oral absorption barrier.


Assuntos
Imunossupressores/farmacologia , Lipídeos/farmacologia , Nanocápsulas/química , Tacrolimo/farmacologia , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Imunossupressores/administração & dosagem , Imunossupressores/química , Imunossupressores/farmacocinética , Infusões Parenterais , Lipídeos/administração & dosagem , Lipídeos/química , Linfócitos/citologia , Linfócitos/efeitos dos fármacos , Masculino , Camundongos , Nanocápsulas/administração & dosagem , Tacrolimo/administração & dosagem , Tacrolimo/química , Tacrolimo/farmacocinética
16.
Drug Dev Ind Pharm ; 40(8): 1011-20, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23672183

RESUMO

Spray drying is a technique used to produce solid particles from liquid solutions, emulsions or suspensions. Buchi Labortechnik developed the latest generation of spray dryers, Nano Spray Dryer B-90. This study aims to obtain, directly, submicron drug particles from an organic solution, employing this equipment and using dexamethasone as a model drug. In addition, we evaluated the influence of both the type of solvent and surfactant on the properties of the powders using a 3(2) full factorial analysis. The particles were obtained with high yields (above 60%), low water content (below 2%) and high drug content (above 80%). The surface tension and the viscosity were strongly influenced by the type of solvent. The highest powder yields were obtained for the highest surface tension and the lowest viscosity of the drug solutions. The use of ionic surfactants led to higher process yields. The laser diffraction technique revealed that the particles deagglomerate into small ones with submicrometric size, (around 1 µm) that was also observed by scanning electron microscopy. Interaction between the raw materials in the spray-dried powders was verified by calorimetric analysis. Thus, it was possible to obtain dexamethasone submicrometric particles by vibrational atomization from organic solution.


Assuntos
Dexametasona/química , Solventes/química , Tensoativos/química , Tecnologia Farmacêutica/métodos , Excipientes/química , Microscopia Eletrônica de Varredura/métodos , Tamanho da Partícula , Pós/química , Soluções/química , Propriedades de Superfície , Tensão Superficial , Viscosidade
17.
J Nanosci Nanotechnol ; 13(12): 8144-53, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24266207

RESUMO

In this study we developed a new drug delivery system for olanzanpine comprised of drug-loaded lipid-core nanocapsules incorporated in a thermosensitive hydrogel, intended to sustain the drug release. Firstly, olanzapine, a hydrophobic drug, was loaded in poly(epsilon-caprolactone) lipid core nanocapsules prepared by interfacial deposition of preformed polymer. The effects of the presence of ethanol and the amounts of sorbitan monostearate and medium-chain triglycerides on the particle size, zeta potential, polydispersity index, presence of microparticles and encapsulation efficiency were investigated using a 2(3) factorial design. The optimized nanocapsules were incorporated into a hydrophilic polymer (Poloxamer 407) dispersion in order to obtain a thermosensitive gel. The formulation containing 0.077 g of sorbitan monostearate, 0.22 ml of medium-chain triglycerides, 3 ml of ethanol and 18% of the thermosensitive polymer was selected according to the physicochemical properties. The rheology and release profiles of the mixed hydrophobic and hydrophilic delivery system were successfully characterized and revealed its great potential for the administration of hydrophobic drugs such as olanzapine with sustained in situ drug release.


Assuntos
Benzodiazepinas/química , Lipídeos/química , Nanocápsulas/química , Reologia , Olanzapina , Tamanho da Partícula , Poloxâmero/química , Poliésteres/química
18.
Int J Cosmet Sci ; 35(1): 105-11, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23075068

RESUMO

Sensory analysis has become a valuable tool in qualifying consumer perception regarding cosmetic products. This study aims to explore the application of discriminative and affective consumers sensory analysis in evaluating the influence of nanoencapsulation on the sensory properties and rheological characteristics of a cosmetic formulation containing lipoic acid. The nanocapsules were prepared by the pre-formed polymer precipitation method. Semisolid formulations were prepared using a silicone emulsion system, and these pseudoplastic fluids were characterized using rheological methods. The panellists (n = 88) analysed the formulations with and without nanoencapsulated lipoic acid as paired comparisons within the discriminative and affective sensory analysis. In these measurements, spreadability, stickiness, oiliness and sulphur odour were evaluated. The panellists had no previous training in conducting these measurements. It was shown that nanotechnology can change some sensory characteristics of the formulations. The spreadability, stickiness and oiliness are the attributes for which the panellists noted differences with statistical significance. The spreadability difference could be due to the results found in the rheological profiles and consistency indexes between formulations. In the discriminative analysis, the panellists could not detect any noticeable differences in the sulphur odour or residual properties between samples, attributes that would influence whether consumers adhered to the selected treatment. Considering affective analysis, the consumers communicated that the formulation containing the nanoencapsulated lipoic acid, which presented less consistency, was preferred based on the reduction in immediate stickiness and residual sulphur odour. The free lipoic acid formulation was preferred in terms of residual oiliness and spreadability.


Assuntos
Química Farmacêutica , Cosméticos , Ácido Tióctico/química , Reologia
19.
Pharmazie ; 67(7): 605-10, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22888517

RESUMO

Levodopa, (S)-2-amino-3-(3,4-dihydroxyphenyl) propanoic acid, is still considered the gold standard treatment for Parkinson's disease. However, oral levodopa shows poor pharmacokinetics and its efficacy becomes problematic with the progression of the disease. Pulmonary delivery using the association of the polymers: chitosan, hyaluronic acid and HPMC, represents a novel approach to overcome this problem. A stability-indicating liquid chromatography method for the quantitative determination of levodopa microparticles for pulmonary delivery was developed as well as its photodegradation kinetics in solution. The developed and validated method was applied for the analyses of the novel formulation as well as for protocols of stability studies.


Assuntos
Antiparkinsonianos/administração & dosagem , Levodopa/administração & dosagem , Administração por Inalação , Antiparkinsonianos/química , Antiparkinsonianos/efeitos da radiação , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Excipientes , Cinética , Levodopa/química , Levodopa/efeitos da radiação , Luz , Limite de Detecção , Nanopartículas , Soluções Farmacêuticas , Fotoquímica , Padrões de Referência , Reprodutibilidade dos Testes , Espectrofotometria Ultravioleta
20.
J Nanosci Nanotechnol ; 12(3): 2059-67, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22755021

RESUMO

The influence of the spray-drying process on the ability of engineered lipid-core nanocapsules to protect tretinoin against UV degradation was evaluated. This approach represents a technological alternative to improve the microbiological stability, storage and transport properties of such formulations. Tretinoin-loaded lipid-core nanocapsules or tretinoin-loaded nanoemulsion were dispersed in lactose (10% w/v) and fed in the spray-drier to obtain a solid product (spray-dried powder containing tretinoin-loaded nanocapsules or nanoemulsion--SD-TTN-NCL or SD-TTN-NE, respectively). SD-TTN-NE showed a lower (p < or = 0.05) percentage of encapsulation (89 +/- 1%) compared to SD-TTN-NCL (94 +/- 2%). Redispersed SD-TTN-NCL and SD-TTN-NE showed z-average sizes of 204 +/- 2 nm and 251 +/- 9 nm, which were close to those of the original suspensions (220 +/- 3 nm and 239 +/- 14 nm, respectively). Similar percentage of photodegradation were determined for tretinoin loaded in nanocapsules (26.15 +/- 4.34%) or in the respective redispersed spray-dried powder (28.73 +/- 6.19 min) after 60 min of UVA radiation exposure (p > 0.05). Our experimental design showed for the first time that spray-dried lipid-core nanocapsules are able to protect tretinoin against UVA radiation, suggesting that the drying process did not alter the supramolecular structure of the lipid-core nanocapsules. Such powders are potential intermediate products for the development of nanomedicines containing tretinoin.

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