Development of methotrexate-loaded cubosomes with improved skin permeation for the topical treatment of rheumatoid arthritis

2019 ◽  
Vol 9 (8) ◽  
pp. 1781-1796 ◽  
Author(s):  
Kumar Janakiraman ◽  
Venkateshwaran Krishnaswami ◽  
Vaidevi Sethuraman ◽  
Vijaya Rajendran ◽  
Ruckmani Kandasamy
2021 ◽  
Vol 15 (1) ◽  
pp. 22
Author(s):  
María Rincón ◽  
Marcelle Silva-Abreu ◽  
Lupe Carolina Espinoza ◽  
Lilian Sosa ◽  
Ana Cristina Calpena ◽  
...  

A biocompatible topical thermo-reversible hydrogel containing Pranoprofen (PF)-loaded nanostructured lipid carriers (NLCs) was studied as an innovative strategy for the topical treatment of skin inflammatory diseases. The PF-NLCs-F127 hydrogel was characterized physiochemically and short-time stability tests were carried out over 60 days. In vitro release and ex vivo human skin permeation studies were carried out in Franz diffusion cells. In addition, a cytotoxicity assay was studied using the HaCat cell line and in vivo tolerance study was performed in humans by evaluating the biomechanical properties. The anti-inflammatory effect of the PF-NLCs-F127 was evaluated in adult male Sprague Daw-ley® rats using a model of inflammation induced by the topical application of xylol for 1 h. The developed PF-NLCs-F127 exhibited a heterogeneous structure with spherical PF-NLCs in the hydrogel. Furthermore, a thermo-reversible behaviour was determined with a gelling temperature of 32.5 °C, being close to human cutaneous temperature and thus favouring the retention of PF. Furthermore, in the ex vivo study, the amount of PF retained and detected in human skin was high and no systemic effects were observed. The hydrogel was found to be non-cytotoxic, showing cell viability of around 95%. The PF-NLCs-F127 is shown to be well tolerated and no signs of irritancy or alterations of the skin’s biophysical properties were detected. The topical application of PF-NLCs-F127 hydrogel was shown to be efficient in an inflammatory animal model, preventing the loss of stratum corneum and reducing the presence of leukocyte infiltration. The results from this study confirm that the developed hydrogel is a suitable drug delivery carrier for the transdermal delivery of PF, improving its dermal retention, opening the possibility of using it as a promising candidate and safer alternative to topical treatment for local skin inflammation and indicating that it could be useful in the clinical environment.


Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 613 ◽  
Author(s):  
Diana Berenguer ◽  
Lilian Sosa ◽  
Magdalena Alcover ◽  
Marcella Sessa ◽  
Lyda Halbaut ◽  
...  

Cutaneous leishmaniasis (CL) is treated with painful intralesional injections of meglumine antimoniate (MA). With the aim of developing an alternative topical treatment for CL, a gel-based formulation with 30% MA was prepared and its physicochemical properties, stability and rheological behavior were studied. The following were assessed: drug release on propylene hydrophilic membranes ex vivo human skin permeation, tolerance in healthy volunteers, cytotoxicity in three cell lines and anti-leishmanial activity against Leishmania infantum promastigotes and amastigotes. The MA gel formulation was found to have suitable pH, and good spreadability and stability. Low quantities of pentavalent antimony (SbV) were observed in release and permeation tests, whereas retention was high in both non-damaged and damaged skin (71,043.69 ± 10,641.57 and 10,728 ± 2254.61 µg/g/cm2 of SbV, respectively). The formulation did not have a toxic effect on the cell lines, and presented lower SbV IC50 values against amastigotes (15.76 ± 4.81 µg/mL) in comparison with the MA solution. The high amount of drug retained in the skin and the SbV IC50 values obtained suggest that this semi-solid dosage form has potential as an alternative treatment of CL.


Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5619
Author(s):  
Eliana B. Souto ◽  
Ana L. R. de Souza ◽  
Fernanda K. dos Santos ◽  
Elena Sanchez-Lopez ◽  
Amanda Cano ◽  
...  

Hyperproliferative skin diseases (HSD) are a group of diseases that include cancers, pre-cancerous lesions and diseases of unknown etiology that present different skin manifestations in terms of the degree and distribution of the injuries. Anti-proliferative agents used to treat these diseases are so diverse, including 5-aminolevulinic acid, 5-fluorouracil, imiquimod, methotrexate, paclitaxel, podophyllotoxin, realgar, and corticosteroids in general. These drugs usually have low aqueous solubility, which consequently decreases skin permeation. Thus, their incorporation in lipid nanocarriers has been proposed with the main objective to increase the effectiveness of topical treatment and reduce side effects. This manuscript aims to describe the advantages of using lipid nanoparticles and liposomes that can be used to load diversity of chemically different drugs for the treatment of HSD.


2021 ◽  
Vol 01 ◽  
Author(s):  
Edson A. T. Almeida ◽  
Ricardo Ferreira-Nunes ◽  
Beatriz R. L. Aguiar ◽  
Paula E. D. dos Reis ◽  
Tais Gratieri ◽  
...  

Background: α-Bisabolol (BIS) is a sesquiterpene extracted from chamomile flowers, which has been used to topically treat burnt skin has been reported. High lipophilicity of BIS, however, is a problem for both skin application and washing. Objective: The present study aimed to prepare and characterize a stable and safe aqueous-based nanoemulsion to incorporate BIS and favor skin penetration focusing on skin burns' topical treatment. Method: Oil-in-water nanoemulsions were obtained from a pseudo-ternary phase diagram. The selected nanoemulsion was characterized (droplet size, PDI, and zeta potential), and the stability was assessed for 60 days at 6ºC and room temperature. The irritability of the formulation was determined by HET-CAM. Skin permeation studies were carried out in vitro intact skin, hot water burn skin, and hot plate burn skin. Results: The nanoemulsion incorporated 1% (w/w) BIS, presented droplets' size of 14.0±0.8 nm (PDI= 0.13±0.02), the zeta potential of +7.5±1.9 mV, and was physically stable over 60 days. The HET-CAM did not show any irritability process provided by the nanoformulation. In the skin permeation experiments, when compared to an oily control solution of BIS, nanoemulsion increased 3.7-fold penetration of the drug in intact skin, likely because the nanoformulation acted as an absorption drug enhancer. On a hot water burn skin model, the increase in drug penetration was 1.7-fold, and in the hot plate burn skin, it was 2.3-fold. Conclusion: The nanoemulsion seems to be a promising alternative for skin burns' topical treatment using this natural active substance.


2004 ◽  
Vol 30 (3) ◽  
pp. 289-296 ◽  
Author(s):  
Luciana S. Ferreira ◽  
Gilson A. Ramaldes ◽  
Elzíria A. Nunan ◽  
Lucas A. M. Ferreira

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