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1.
Actas dermo-sifiliogr. (Ed. impr.) ; 115(2): 150-158, feb. 2024. tab, graf
Article in English | IBECS | ID: ibc-230312

ABSTRACT

Background Dupilumab is a new targeted therapy for severe atopic dermatitis (AD) with limited real-world evidence. Objective Explore our experience with dupilumab for AD in clinical practice at a tertiary care center. Material and method Unicentric observational retrospective study including adult and pediatric patients with severe AD receiving dupilumab between December 2017 and December 2021. The Eczema Area and Severity Index (EASI) score, Pruritus Numerical Rating Scale (P-NRS) and Sleep disturbance Numerical Rating Scale (S-NRS) were recovered to assess severity and response. Results Fifty-nine patients received dupilumab: 52, 48, 26 and 13 patients reached 6, 12, 24 and 36 months of treatment, respectively. The EASI-75 response rates were 94.2%, 95.8%, 92.3% and 100% at months 6, 12, 24 and 36. The EASI-90 response rates were 63.5%, 72.9%, 84.6% and 92.3% at months 6, 12, 24 and 36. The EASI <7 response rates were 92.3%, 91.7%, 88.5% and 100% at months 6, 12, 24 and 36. The P-NRS ≥4 reduction rates were 86%, 87.5%, 92.3% and 100% at months 6, 12, 24 and 36. The S-NRS ≥4 reduction rates were 82.7%, 85.4%, 100% and 100% at months 6, 12, 24 and 36. Adverse events were mild and occurred in 20.3% of patients, all of them adults. Conclusion Our findings support dupilumab's favorable efficacy and tolerability profile in clinical practice. Dupilumab offers a rapid and sustained response, regardless of combined therapy. Longer follow-ups are still required to adequately assess its performance (AU)


Antecedentes Dupilumab es una nueva terapia dirigida para la dermatitis atópica (DA) grave con una evidencia en la vida real aún limitada. Objetivo Explorar nuestra experiencia con dupilumab para la DA en práctica clínica en un centro terciario. Material y método Estudio observacional retrospectivo y unicéntrico que incluye pacientes adultos y pediátricos con DA grave en tratamiento con dupilumab entre diciembre de 2017 y diciembre de 2021. La gravedad y la respuesta se evaluaron con las escalas Eczema Area and Severity Index (EASI), Pruritus Numerical Rating Scale y Sleep Disturbance Numerical Rating Scale. Resultado Cincuenta y nueve pacientes recibieron dupilumab: 52, 48, 26 y 13 pacientes alcanzaron los 6, 12, 24 y 36 meses de tratamiento, respectivamente. La tasa de EASI-75 fue del 94,2; 95,8; 92,3 y 100% a los 6, 12, 24 y 36 meses, respectivamente. La tasa de EASI-90 fue del 63,5; 72,9; 84,6 y 92,3% a los 6, 12, 24 y 36 meses, respectivamente. La tasa de EASI <7 fue del 92,3; 91,7; 88,5 y 100% a los 6, 12, 24 y 36 meses, respectivamente. La Pruritus Numerical Rating Scale ≥4 fue del 86; 87,5; 92,3 y 100% a los 6, 12, 24 y 36 meses, respectivamente. La tasa de reducción Sleep Disturbance Numerical Rating Scale ≥4 fue del 82,7; 85,4; 100 y 100% a los 6, 12, 24 y 36 meses, respectivamente. Los eventos adversos fueron leves y ocurrieron en el 20,3% de los pacientes, todos adultos. Conclusión Nuestros hallazgos apoyan el perfil favorable de eficacia y tolerabilidad de dupilumab en práctica clínica real. Dupilumab ofrece una respuesta rápida y mantenida, independientemente del uso de terapia combinada. Se requieren seguimientos más prolongados para evaluar su funcionamiento a largo plazo (AU)


Subject(s)
Humans , Male , Female , Child , Adolescent , Antibodies, Monoclonal, Humanized/therapeutic use , Dermatitis, Atopic/drug therapy , Severity of Illness Index , Retrospective Studies , Treatment Outcome
2.
Actas dermo-sifiliogr. (Ed. impr.) ; 115(2): t150-t158, feb. 2024. tab, graf
Article in Spanish | IBECS | ID: ibc-230313

ABSTRACT

Antecedentes Dupilumab es una nueva terapia dirigida para la dermatitis atópica (DA) grave con una evidencia en la vida real aún limitada. Objetivo Explorar nuestra experiencia con dupilumab para la DA en práctica clínica en un centro terciario. Material y método Estudio observacional retrospectivo y unicéntrico que incluye pacientes adultos y pediátricos con DA grave en tratamiento con dupilumab entre diciembre de 2017 y diciembre de 2021. La gravedad y la respuesta se evaluaron con las escalas Eczema Area and Severity Index (EASI), Pruritus Numerical Rating Scale y Sleep Disturbance Numerical Rating Scale. Resultados Cincuenta y nueve pacientes recibieron dupilumab: 52, 48, 26 y 13 pacientes alcanzaron los 6, 12, 24 y 36 meses de tratamiento, respectivamente. La tasa de EASI-75 fue del 94,2; 95,8; 92,3 y 100% a los 6, 12, 24 y 36 meses, respectivamente. La tasa de EASI-90 fue del 63,5; 72,9; 84,6 y 92,3% a los 6, 12, 24 y 36 meses, respectivamente. La tasa de EASI <7 fue del 92,3; 91,7; 88,5 y 100% a los 6, 12, 24 y 36 meses, respectivamente. La Pruritus Numerical Rating Scale ≥4 fue del 86; 87,5; 92,3 y 100% a los 6, 12, 24 y 36 meses, respectivamente. La tasa de reducción Sleep Disturbance Numerical Rating Scale ≥4 fue del 82,7; 85,4; 100 y 100% a los 6, 12, 24 y 36 meses, respectivamente. Los eventos adversos fueron leves y ocurrieron en el 20,3% de los pacientes, todos adultos. Conclusión Nuestros hallazgos apoyan el perfil favorable de eficacia y tolerabilidad de dupilumab en práctica clínica real. Dupilumab ofrece una respuesta rápida y mantenida, independientemente del uso de terapia combinada. Se requieren seguimientos más prolongados para evaluar su funcionamiento a largo plazo (AU)


Background Dupilumab is a new targeted therapy for severe atopic dermatitis (AD) with limited real-world evidence. Objective Explore our experience with dupilumab for AD in clinical practice at a tertiary care center. Material and method Unicentric observational retrospective study including adult and pediatric patients with severe AD receiving dupilumab between December 2017 and December 2021. The Eczema Area and Severity Index (EASI) score, Pruritus Numerical Rating Scale (P-NRS) and Sleep disturbance Numerical Rating Scale (S-NRS) were recovered to assess severity and response. Results Fifty-nine patients received dupilumab: 52, 48, 26 and 13 patients reached 6, 12, 24 and 36 months of treatment, respectively. The EASI-75 response rates were 94.2%, 95.8%, 92.3% and 100% at months 6, 12, 24 and 36. The EASI-90 response rates were 63.5%, 72.9%, 84.6% and 92.3% at months 6, 12, 24 and 36. The EASI <7 response rates were 92.3%, 91.7%, 88.5% and 100% at months 6, 12, 24 and 36. The P-NRS ≥4 reduction rates were 86%, 87.5%, 92.3% and 100% at months 6, 12, 24 and 36. The S-NRS ≥4 reduction rates were 82.7%, 85.4%, 100% and 100% at months 6, 12, 24 and 36. Adverse events were mild and occurred in 20.3% of patients, all of them adults. Conclusion Our findings support dupilumab's favorable efficacy and tolerability profile in clinical practice. Dupilumab offers a rapid and sustained response, regardless of combined therapy. Longer follow-ups are still required to adequately assess its performance (AU)


Subject(s)
Humans , Male , Female , Child , Adolescent , Antibodies, Monoclonal, Humanized/therapeutic use , Dermatitis, Atopic/drug therapy , Severity of Illness Index , Treatment Outcome , Retrospective Studies
3.
Actas Dermosifiliogr ; 115(2): T150-T158, 2024 Feb.
Article in English, Spanish | MEDLINE | ID: mdl-38048951

ABSTRACT

BACKGROUND: Dupilumab is a new targeted therapy for severe atopic dermatitis (AD) with limited real-world evidence. OBJECTIVE: Explore our experience with dupilumab for AD in clinical practice at a tertiary care center. MATERIAL AND METHOD: Unicentric observational retrospective study including adult and pediatric patients with severe AD receiving dupilumab between December 2017 and December 2021. The Eczema Area and Severity Index (EASI) score, Pruritus Numerical Rating Scale (P-NRS) and Sleep disturbance Numerical Rating Scale (S-NRS) were recovered to assess severity and response. RESULTS: Fifty-nine patients received dupilumab: 52, 48, 26 and 13 patients reached 6, 12, 24 and 36 months of treatment, respectively. The EASI-75 response rates were 94.2%, 95.8%, 92.3% and 100% at months 6, 12, 24 and 36. The EASI-90 response rates were 63.5%, 72.9%, 84.6% and 92.3% at months 6, 12, 24 and 36. The EASI <7 response rates were 92.3%, 91.7%, 88.5% and 100% at months 6, 12, 24 and 36. The P-NRS ≥4 reduction rates were 86%, 87.5%, 92.3% and 100% at months 6, 12, 24 and 36. The S-NRS ≥4 reduction rates were 82.7%, 85.4%, 100% and 100% at months 6, 12, 24 and 36. Adverse events were mild and occurred in 20.3% of patients, all of them adults. CONCLUSION: Our findings support dupilumab's favorable efficacy and tolerability profile in clinical practice. Dupilumab offers a rapid and sustained response, regardless of combined therapy. Longer follow-ups are still required to adequately assess its performance.


Subject(s)
Dermatitis, Atopic , Adult , Humans , Child , Dermatitis, Atopic/drug therapy , Retrospective Studies , Severity of Illness Index , Antibodies, Monoclonal, Humanized/adverse effects , Pruritus/chemically induced , Treatment Outcome , Double-Blind Method
4.
Actas Dermosifiliogr ; 115(2): 150-158, 2024 Feb.
Article in English, Spanish | MEDLINE | ID: mdl-37858860

ABSTRACT

BACKGROUND: Dupilumab is a new targeted therapy for severe atopic dermatitis (AD) with limited real-world evidence. OBJECTIVE: Explore our experience with dupilumab for AD in clinical practice at a tertiary care center. MATERIAL AND METHOD: Unicentric observational retrospective study including adult and pediatric patients with severe AD receiving dupilumab between December 2017 and December 2021. The Eczema Area and Severity Index (EASI) score, Pruritus Numerical Rating Scale (P-NRS) and Sleep disturbance Numerical Rating Scale (S-NRS) were recovered to assess severity and response. RESULTS: Fifty-nine patients received dupilumab: 52, 48, 26 and 13 patients reached 6, 12, 24 and 36 months of treatment, respectively. The EASI-75 response rates were 94.2%, 95.8%, 92.3% and 100% at months 6, 12, 24 and 36. The EASI-90 response rates were 63.5%, 72.9%, 84.6% and 92.3% at months 6, 12, 24 and 36. The EASI <7 response rates were 92.3%, 91.7%, 88.5% and 100% at months 6, 12, 24 and 36. The P-NRS ≥4 reduction rates were 86%, 87.5%, 92.3% and 100% at months 6, 12, 24 and 36. The S-NRS ≥4 reduction rates were 82.7%, 85.4%, 100% and 100% at months 6, 12, 24 and 36. Adverse events were mild and occurred in 20.3% of patients, all of them adults. CONCLUSION: Our findings support dupilumab's favorable efficacy and tolerability profile in clinical practice. Dupilumab offers a rapid and sustained response, regardless of combined therapy. Longer follow-ups are still required to adequately assess its performance.


Subject(s)
Dermatitis, Atopic , Adult , Child , Humans , Antibodies, Monoclonal, Humanized/adverse effects , Dermatitis, Atopic/drug therapy , Double-Blind Method , Pruritus/chemically induced , Retrospective Studies , Severity of Illness Index , Treatment Outcome
5.
Actas dermo-sifiliogr. (Ed. impr.) ; 111(3): 249-253, abr. 2020. tab, graf
Article in Spanish | IBECS | ID: ibc-191528

ABSTRACT

ANTECEDENTES: La asociación entre los inhibidores de la dipeptidil peptidasa 4 (iDPP-4) y el penfigoide ampolloso (PA) se ha demostrado en varios estudios. El objetivo principal de este estudio era estimar el uso del tratamiento con iDPP-4i en pacientes diagnosticados de PA en nuestro entorno. MATERIAL Y MÉTODOS: Seleccionamos pacientes diagnosticados histológicamente de PA en nuestro departamento entre octubre de 2015 y octubre de 2018. Realizamos una revisión retrospectiva para evaluar los datos clínicos-epidemiológicos y los patrones de inmunofluorescencia directa (IFD). RESULTADOS: De los 70 pacientes diagnosticados con PA durante el período de estudio, el 50% eran diabéticos y el 88,57% de ellos estaban siendo tratados con un iDPP-4 en el momento del diagnóstico de PA. El iDPP-4 más frecuente era la linagliptina (utilizada en el 18,6% de los pacientes), seguida de la vildagliptina (el 17,1%). La mediana de tiempo de latencia entre el inicio del tratamiento con iDPP-4 y el diagnóstico de PA fue de 27,5 meses, siendo de 16 meses para la linagliptina y 39 meses para la vildagliptina (log Rank < 0,01). La IFD fue negativaUn resultado negativo de DIF fue significativamente más común en pacientes que no fueron tratados con un DPP-4i. El patrón DIF más fuertemente (y significativamente) asociado con el tratamiento con DPP-4i fueron los depósitos lineales de inmunoglobulina G a lo largo de la unión dermoepidérmica. El tratamiento con DPP-4i se retiró en el 87% de los pacientes y el 96% de ellos logró una respuesta completa. CONCLUSIÓN: El tratamiento con DPP-4i es muy común en pacientes con BP en nuestro entorno. El período de latencia entre el inicio del tratamiento y el inicio de la PA parece ser más corto con linagliptina que con otros tipos de gliptinas. Los pacientes que reciben tratamiento con DPP-4i pueden mostrar patrones DIF diferentes a los que no reciben tratamiento


BACKGROUND: The association between dipeptidyl peptidase 4 inhibitors (DPP-4i) and bullous pemphigoid (BP) has been demonstrated in several studies. The main aim of this study was to estimate the use of DPP-4i treatment in patients diagnosed with BP in our setting. METHODS: We selected patients histologically diagnosed with BP in our department between October 2015 and October 2018 and performed a retrospective chart review to assess clinical and epidemiological data and direct immunofluorescence (DIF) patterns. RESULTS: Of the 70 patients diagnosed with BP during the study period, 50% were diabetic and 88.57% of these were being treated with a DPP-4i when diagnosed with BP. The most common DPP-4i was linagliptin (used in 18.6% of patients), followed by vildagliptin (17.1%). The median latency period between initiation of DPP-4i treatment and diagnosis of BP was 27.5 months for all treatments, 16 months for linagliptin, and 39 months for vildagliptin (log rank < 0.01). A negative DIF result was significantly more common in patients not being treated with a DPP-4i. The DIF pattern most strongly (and significantly) associated with DPP-4i treatment was linear immunoglobulin G deposits along the dermal-epidermal junction. DPP-4i treatment was withdrawn in 87% of patients and 96% of these achieved a complete response. CONCLUSIONS: DPP-4i treatment is very common in patients with BP in our setting. The latency period between start of treatment and onset of BP seems to be shorter with linagliptin than with other types of gliptins. Patients receiving DPP-4i treatment may show different DIF patterns to those not receiving treatment


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Pemphigoid, Bullous/epidemiology , Fluorescent Antibody Technique, Direct/standards , Pemphigoid, Bullous/chemically induced , Retrospective Studies , Dipeptidyl-Peptidase IV Inhibitors/administration & dosage
6.
Actas Dermosifiliogr (Engl Ed) ; 111(3): 249-253, 2020 Apr.
Article in English, Spanish | MEDLINE | ID: mdl-31864538

ABSTRACT

BACKGROUND: The association between dipeptidyl peptidase 4 inhibitors (DPP-4i) and bullous pemphigoid (BP) has been demonstrated in several studies. The main aim of this study was to estimate the use of DPP-4i treatment in patients diagnosed with BP in our setting. METHODS: We selected patients histologically diagnosed with BP in our department between October 2015 and October 2018 and performed a retrospective chart review to assess clinical and epidemiological data and direct immunofluorescence (DIF) patterns. RESULTS: Of the 70 patients diagnosed with BP during the study period, 50% were diabetic and 88.57% of these were being treated with a DPP-4i when diagnosed with BP. The most common DPP-4i was linagliptin (used in 18.6% of patients), followed by vildagliptin (17.1%). The median latency period between initiation of DPP-4i treatment and diagnosis of BP was 27.5 months for all treatments, 16 months for linagliptin, and 39 months for vildagliptin (log rank < 0.01). A negative DIF result was significantly more common in patients not being treated with a DPP-4i. The DIF pattern most strongly (and significantly) associated with DPP-4i treatment was linear immunoglobulin G deposits along the dermal-epidermal junction. DPP-4i treatment was withdrawn in 87% of patients and 96% of these achieved a complete response. CONCLUSIONS: DPP-4i treatment is very common in patients with BP in our setting. The latency period between start of treatment and onset of BP seems to be shorter with linagliptin than with other types of gliptins. Patients receiving DPP-4i treatment may show different DIF patterns to those not receiving treatment.


Subject(s)
Dipeptidyl-Peptidase IV Inhibitors , Pemphigoid, Bullous , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Humans , Linagliptin/adverse effects , Pemphigoid, Bullous/chemically induced , Retrospective Studies , Vildagliptin
7.
Actas dermo-sifiliogr. (Ed. impr.) ; 110(9): 728-733, nov. 2019. ilus
Article in Spanish | IBECS | ID: ibc-185564

ABSTRACT

Los hemangiomas infantiles son los tumores benignos más frecuentes en la población pediátrica. Cuando afectan al área lumbar y perineal, algunos casos pueden asociarse a alguna malformación subyacente como una disrafia espinal oculta. El manejo de estos hemangiomas carece de consenso. Describimos 3 casos de niños con hemangiomas lumbosacros y perineales con anomalías en la resonancia magnética y revisamos la literatura para valorar qué pruebas y en qué momento se deben realizar para completar el estudio en estos pacientes. Por lo general, se solicita una ecografía lo más precozmente posible, ya que esta técnica no es posible realizarla una vez que los elementos espinales posteriores se han osificado, lo que generalmente ocurre a los 6 meses de edad. La resonancia magnética es la prueba de referencia para diagnosticar una disrafia espinal oculta. De acuerdo con la literatura, la edad media para este examen debe ser alrededor de los 6 meses, cuando la formación de grasa en el filum terminale se ha visto incrementada. En nuestra opinión, se debería realizar una resonancia magnética a los 6 meses de edad en todos los niños con hemangioma lumbar o perineal, independientemente del tamaño de la lesión, la ausencia de síntomas neurológicos o los resultados de la ecografía


Cutaneous hemangiomas are the most frequent benign tumors in children. When they affect the lumbar and perineal area some cases can be associated with an occult spinal dysraphism. The management of these hemangiomas lack consensus. We report 3 cases of children with lumbosacral and perineal hemangiomas with magnetic resonance image abnormalities and we review the literature to find out the type and timing of tests that should be performed to complete the study in these patients. Ultrasound is typically requested as young as possible, as this imaging technique is not possible 11 the posterior spinal elements have ossified. MRI is the gold standard for diagnosing occult spinal dysraphism. According to the literature, the mean age for MRI screening should be around 6 months, when the fat formation in the filum terminale is expanded. In our opinion, an MRI scan should be performed at 6 months of age in every children with lumbar or perineal hemangioma regardless the lesion size, neurological symptoms or the ultrasound results


Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Hemangioma/diagnostic imaging , Hemangioma/drug therapy , Magnetic Resonance Spectroscopy/methods , Lumbosacral Plexus/diagnostic imaging , Lumbosacral Plexus/pathology , Spinal Dysraphism/diagnostic imaging , Propranolol/administration & dosage , Neurosurgery
8.
AAPS PharmSciTech ; 20(7): 294, 2019 Aug 20.
Article in English | MEDLINE | ID: mdl-31432298

ABSTRACT

Liposomes with their capacity to anchor gold nanoparticles (AuNPs) onto their surface are used in the treatment of several pathologies such as cancer. The objective of this work was the optimization of the vesicle composition by using cationic agents in order to reinforce the anchoring process of AuNPs, and for the study of the influence of local temperature and vesicle size on drug release. A Plackett-Burman design was conducted to determine the optimal composition for the anchoring of AuNPs. A comprehensive study of the influence of lipid bilayer composition on the surface charge, size, and polydispersity index (PdI) of liposomes was carried out. Afterwards, in vitro release studies by dialysis were performed and several release parameters were evaluated as a function of temperature. Cholesterol was fixed as the rigid agent and Didodecyldimethylammonium bromide (DDAB) was selected as the cationic lipid into the liposome bilayer. Photomicrographs revealed that DDAB facilitated the anchoring of AuNPs onto the liposomal surface. The anchoring of AuNPs also enhanced the amount and rate of calcein released, especially in extruded samples, at several incubating temperatures. In addition, it was observed that both the anchoring of AuNPs and the calcein release were improved by increasing the surface of the vesicles. The contributions of liposome composition (DDAB inclusion, incubation temperature, anchoring of AuNPs) and size and surface availability of the vesicles on calcein release could be used to design improved lipid nanostructures for the controlled release of anticancer drugs.


Subject(s)
Gold/chemistry , Metal Nanoparticles/chemistry , Quaternary Ammonium Compounds/administration & dosage , Drug Liberation , Humans , Lipid Bilayers/chemistry , Liposomes/chemistry , Quaternary Ammonium Compounds/chemistry
9.
Actas Dermosifiliogr (Engl Ed) ; 110(9): 728-733, 2019 Nov.
Article in English, Spanish | MEDLINE | ID: mdl-30449349

ABSTRACT

Cutaneous hemangiomas are the most frequent benign tumors in children. When they affect the lumbar and perineal area some cases can be associated with an occult spinal dysraphism. The management of these hemangiomas lack consensus. We report 3 cases of children with lumbosacral and perineal hemangiomas with magnetic resonance image abnormalities and we review the literature to find out the type and timing of tests that should be performed to complete the study in these patients. Ultrasound is typically requested as young as possible, as this imaging technique is not possible 11the posterior spinal elements have ossified. MRI is the gold standard for diagnosing occult spinal dysraphism. According to the literature, the mean age for MRI screening should be around 6 months, when the fat formation in the filum terminale is expanded. In our opinion, an MRI scan should be performed at 6 months of age in every children with lumbar or perineal hemangioma regardless the lesion size, neurological symptoms or the ultrasound results.


Subject(s)
Hemangioma/diagnostic imaging , Skin Neoplasms/diagnostic imaging , Adrenergic beta-Antagonists/therapeutic use , Female , Hemangioma/drug therapy , Humans , Infant , Lipoma/diagnostic imaging , Lumbosacral Region/diagnostic imaging , Male , Perineum/diagnostic imaging , Propranolol/therapeutic use , Skin Neoplasms/drug therapy , Spina Bifida Occulta/diagnostic imaging
10.
Eur J Pharm Sci ; 111: 186-194, 2018 Jan 01.
Article in English | MEDLINE | ID: mdl-28923571

ABSTRACT

The purpose of this study was to compare the in vivo efficacy of several timolol (TM)-loaded liposomal formulations with current TM antiglaucoma treatment (aqueous 0.5% w/v eye drops). In this study, conventional liposomes (CL) and deformable liposomes, without (DL1) and with ethanol (DL2) were prepared and characterized. In addition, in vitro release and permeation studies, as well as in vivo lowering intraocular pressure (IOP) and biocompatibility studies were performed. It was found that the quali and quantitative lipid bilayer composition played a significant role in modifying the physical properties of vesicles. The deformability study and electronic microscopy images revealed that membrane elasticity of DL1 and DL2 was much higher than CL. However, in vitro permeation results showed that the flux and permeability coefficient were significantly higher in CL compared to DL. The IOP study revealed that TM-loaded CL showed the best pharmacological activity, in comparison to deformable vesicles. Compared to the eye drops, CL formulation could equally reduce the IOP but using a concentration 10-fold lower, whereas the effective time was significantly longer. In addition, the formulations showed no irritant effects after instillation on the ocular surface.


Subject(s)
Adrenergic beta-Antagonists/administration & dosage , Liposomes/chemistry , Nanostructures/chemistry , Timolol/administration & dosage , Administration, Ophthalmic , Adrenergic beta-Antagonists/pharmacokinetics , Animals , Dose-Response Relationship, Drug , Ethanol/adverse effects , Ethanol/chemistry , Liposomes/adverse effects , Male , Nanostructures/adverse effects , Ophthalmic Solutions , Rabbits , Surface-Active Agents/adverse effects , Surface-Active Agents/chemistry , Timolol/pharmacokinetics
11.
Drug Dev Ind Pharm ; 42(10): 1683-94, 2016 Oct.
Article in English | MEDLINE | ID: mdl-26981839

ABSTRACT

The purpose of this work was to analyze the deformability properties of different timolol maleate (TM)-loaded transfersomes by extrusion. This was performed because elastic liposomes may contribute to the elevation of amount and rate of drug permeation through the corneal membrane. This paper describes the optimization of a transfersome formulation by use of Taguchi orthogonal experimental design and two different statistical analysis approaches were utilized. The amount of cholesterol (F1), the amount of edge-activator (F2), the distribution of the drug into the vesicle (F3), the addition of stearylamine (F4) and the type of edge-activator (F5) were selected as causal factors. The deformability index, the phosphorous recovery, the vesicle size, the polydispersity index, the zeta potential and percentage of drug entrapped were fixed as the dependent variables and these responses were evaluated for each formulation. Two different statistical analysis approaches were applied. The better statistical approach was determined by comparing their prediction errors, where regression analysis provided better optimized responses than marginal means. From the study, an optimized formulation of TM-loaded transfersomes was prepared and obtained for the proposed ophthalmic delivery for the treatment of open angle glaucoma. It was found that the lipid to surfactant ratio and type of surfactant are the main key factors for determining the flexibility of the bilayer of transfersomes. From in vitro permeation studies, we can conclude that TM-loaded transfersomes may enhance the corneal transmittance and improve the bioavailability of conventional TM delivery.


Subject(s)
Drug Carriers , Liposomes/chemistry , Surface-Active Agents/chemistry , Timolol/analysis , Administration, Cutaneous , Biological Availability , Drug Delivery Systems , Surface-Active Agents/administration & dosage , Timolol/chemistry
13.
Pharm Dev Technol ; 21(7): 823-831, 2016 Nov.
Article in English | MEDLINE | ID: mdl-26135385

ABSTRACT

The use of lipid nanosystems as drug delivery to the central nervous system may be advantageous over the current strategies. The aim of this study was to develop and characterize functionalized liposomes for treatment of brain diseases. The covalent method of coupling IgG to liposomes via the derivatized lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[4-(p-maleimidophenyl)butyramide](MPB-PE) was investigated. Optimized coupling conditions are shown to result in the efficient conjugation of IgG to liposomes containing low concentrations of MPB-PE (3/1 SH:IgG). The qualitative analysis has shown that after the extrusion process, more homogeneous populations of vesicles have been obtained with a nanometric size suitable to be effective to further anchor the protein. Negative values of zeta potential demonstrate that they are stable systems. Lyophilization was used to maintain the stability of the formulation. These very interesting results encourage further investigations to formulate peptide- and protein-loaded immunoliposomes, making targeting of liposomes as an attractive approach for brain drug delivery.


Subject(s)
Brain/drug effects , Lipids/chemistry , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Brain Diseases/drug therapy , Chemistry, Pharmaceutical/methods , Drug Delivery Systems/methods , Immunoglobulin G/chemistry , Liposomes/administration & dosage , Liposomes/chemistry , Particle Size , Phosphatidylethanolamines/chemistry
14.
Actas dermo-sifiliogr. (Ed. impr.) ; 105(6): 590-596, jul.-ago. 2014. tab, ilus
Article in Spanish | IBECS | ID: ibc-125171

ABSTRACT

OBJETIVO: El objetivo de este trabajo es el estudio descriptivo de los pacientes con dermatitis alérgica de contacto por níquel que han sido atendidos en un hospital de referencia en dermatología en un periodo de 10 años. MATERIAL Y MÉTODOS: Se han analizado los datos de todos los pacientes parchados con la batería estándar del Grupo Español de Investigación en Dermatitis de Contacto y Alérgica Cutánea (GEIDAC) que incluye un parche con sulfato de níquel en vaselina al 5%, a partir de la base de datos informatizada de la sección de alergia cutánea de nuestro servicio. Para conocer la implicación de diferentes objetos metálicos en el origen de la dermatitis utilizamos un método colorimétrico llamado test de dimetilglioxima (DMGO). RESULTADOS: Durante el periodo de estudio se ha explorado mediante pruebas epicutáneas con la batería estándar del GEIDAC a 3.404 pacientes. Del total de pacientes parchados un 24,2% presentaron un parche positivo para sulfato de níquel al 5% en vaselina. Sin embargo, de los 824 pacientes sensibilizados al níquel solo en 57 de ellos (6,9%) se pudo demostrar una asociación de la sensibilización con la dermatitis por la que consultaban. CONCLUSIONES: Solo se identificó relevancia presente en un pequeño porcentaje de pacientes con positividad al níquel en las pruebas epicutáneas. Destacamos la utilidad del test de DMGO como método de ayuda para establecer la relevancia de la positividad del parche con níquel, e incluso para conocer el objeto causante de dicha dermatitis


OBJECTIVE: The aim of this study based on the records of the dermatology department of a tertiary referral hospital was to describe patients treated for allergic contact dermatitis induced by nickel between 2000 and 2010. MATERIALS AND METHODS: From records of the skin allergy section of the dermatology department we extracted and analyzed information for patients who underwent patch testing with the standard series of the Spanish Contact Dermatitis Research Group (GEIDAC), which includes a patch with 5% nickel sulfate in petroleum jelly. The possibility that nickel release from various objects might have triggered the patient's dermatitis was assessed with the dimethylglyoxime spot test, which reveals a reddish precipitate if the metal is present. RESULTS: A total of 3,404 patients underwent GEIDAC patch testing during the study period; 24.2% had positive reactions to the patch containing 5% nickel sulfate in petroleum jelly. However, the contact dermatitis could be attributed to nickel in only 57 of the 824 patients (6.9%) who showed sensitization to nickel. CONCLUSIONS: Patch-test evidence of sensitization was found to be clinically relevant in only a small percentage of patients. We emphasize the usefulness of the dimethylglyoxime test to help establish the relevance of a positive nickel patch test. This test is even useful for identifying the specific object responsible for a patient's dermatitis


Subject(s)
Humans , Nickel/adverse effects , Dermatitis, Allergic Contact/diagnosis , Patch Tests/methods , Risk Factors
15.
Clin Exp Dermatol ; 39(4): 484-7, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24758493

ABSTRACT

Epstein-Barr virus-positive (EBV) diffuse large B-cell lymphoma (DLCBL) of the elderly is a newly described lymphoproliferative disorder that arises in elderly patients without a predisposing immunodeficiency. Clinical features at presentation may include lymphadenopathy, B-symptoms and extranodal involvement. The main sites of extranodal involvement are the skin, lung, tonsil and stomach. Histopathological findings include atypical large lymphoid cells with variable amounts of reactive cells, such as small lymphocytes, plasma cells and histiocytes. The neoplastic cells are positive for CD20, and in situ hybridization for EBV-encoded RNA is positive in the majority of neoplastic cells. We present a new case of EBV-positive DLBCL in an 85-year-old man, who presented to our clinic with a 2-month history of asymptomatic cutaneous lesions involving his face and scalp.


Subject(s)
Epstein-Barr Virus Infections/pathology , Facial Neoplasms/virology , Head and Neck Neoplasms/virology , Lymphoma, Large B-Cell, Diffuse/virology , Scalp , Skin Neoplasms/virology , Aged, 80 and over , Diagnosis, Differential , Facial Neoplasms/pathology , Head and Neck Neoplasms/pathology , Humans , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Skin Neoplasms/pathology
16.
Actas Dermosifiliogr ; 105(6): 590-6, 2014.
Article in English, Spanish | MEDLINE | ID: mdl-24530124

ABSTRACT

OBJECTIVE: The aim of this study based on the records of the dermatology department of a tertiary referral hospital was to describe patients treated for allergic contact dermatitis induced by nickel between 2000 and 2010. MATERIALS AND METHODS: From records of the skin allergy section of the dermatology department we extracted and analyzed information for patients who underwent patch testing with the standard series of the Spanish Contact Dermatitis Research Group (GEIDAC), which includes a patch with 5% nickel sulfate in petroleum jelly. The possibility that nickel release from various objects might have triggered the patient's dermatitis was assessed with the dimethylglyoxime spot test, which reveals a reddish precipitate if the metal is present. RESULTS: A total of 3,404 patients underwent GEIDAC patch testing during the study period; 24.2% had positive reactions to the patch containing 5% nickel sulfate in petroleum jelly. However, the contact dermatitis could be attributed to nickel in only 57 of the 824 patients (6.9%) who showed sensitization to nickel. CONCLUSIONS: Patch-test evidence of sensitization was found to be clinically relevant in only a small percentage of patients. We emphasize the usefulness of the dimethylglyoxime test to help establish the relevance of a positive nickel patch test. This test is even useful for identifying the specific object responsible for a patient's dermatitis.


Subject(s)
Dermatitis, Allergic Contact/diagnosis , Dermatitis, Allergic Contact/etiology , Nickel/adverse effects , Adolescent , Adult , Female , Humans , Male , Middle Aged , Oximes , Patch Tests , Retrospective Studies , Tertiary Care Centers , Time Factors , Young Adult
17.
J Pharm Biomed Anal ; 72: 251-60, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23063308

ABSTRACT

In this paper, a novel, precise, specific, accurate and rapid reversed-phase high performance liquid chromatographic method was developed, optimized and validated for determining sumatriptan succinate in niosomes with the best chromatographic peak resolution, reduced run time and low cost of analysis. The formulation has been previously optimized in terms of composition and preparation technique to obtain a high drug encapsulation efficiency and adequate vesicle size distribution. This method showed the best resolution by using Spherisorb OSD2 C18 column (250 mm × 4.6 mm, 5 µm) using phosphate buffer (0.05 M):acetonitrile (80:20, v/v; pH adjusted to 6.0) as a mobile phase at a flow rate of 1 mL/min and wavelength of 214 nm. The main objective of this research was to demonstrate the robustness of the reversed-phase HPLC method development by applying the Taguchi robust methodology. The signal-to-noise ratio (S/N) was employed as a quality measurement. This tool permits to establish the influence of some selected factors (acetonitrile:phosphate ratio, pH buffer, oven temperature and flow rate) on two responses (peak areas and retention time). On the basis of the results obtained, we can conclude that this analytical method was robust for all the factors studies, as exception of the flow rate, where the higher quality was obtained for the fewer values (0.8 mL/min). Therefore, this parameter must be carefully controlled when this method was employed, to avoid any modification in the peak areas overall.


Subject(s)
Chromatography, High Pressure Liquid/methods , Chromatography, Reverse-Phase/methods , Liposomes/chemistry , Sumatriptan/chemistry , Chemistry, Pharmaceutical/methods , Reproducibility of Results , Sensitivity and Specificity , Signal-To-Noise Ratio , Sumatriptan/analysis
18.
ScientificWorldJournal ; 2012: 605610, 2012.
Article in English | MEDLINE | ID: mdl-22645438

ABSTRACT

Formulation process is a very complex activity which sometimes implicates taking decisions about parameters or variables to obtain the best results in a high variability or uncertainty context. Therefore, robust optimization tools can be very useful for obtaining high quality formulations. This paper proposes the optimization of different responses through the robust Taguchi method. Each response was evaluated like a noise variable, allowing the application of Taguchi techniques to obtain a response under the point of view of the signal to noise ratio. A L(18) Taguchi orthogonal array design was employed to investigate the effect of eight independent variables involved in the formulation of alginate-Carbopol beads. Responses evaluated were related to drug release profile from beads (t(50%) and AUC), swelling performance, encapsulation efficiency, shape and size parameters. Confirmation tests to verify the prediction model were carried out and the obtained results were very similar to those predicted in every profile. Results reveal that the robust optimization is a very useful approach that allows greater precision and accuracy to the desired value.


Subject(s)
Acrylic Resins/chemistry , Alginates/chemistry , Chemistry, Pharmaceutical/methods , Acrylic Resins/administration & dosage , Alginates/administration & dosage , Algorithms , Cations , Delayed-Action Preparations , Drug Compounding/methods , Drug Delivery Systems , Glucuronic Acid/administration & dosage , Glucuronic Acid/chemistry , Hexuronic Acids/administration & dosage , Hexuronic Acids/chemistry , Microscopy, Electron, Scanning/methods , Microspheres , Models, Statistical , Polymers/chemistry , Reproducibility of Results , Signal-To-Noise Ratio , Temperature
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