07343ec4a794a073efae09c4a89f21cd pmc_35056079.pdf 84dfdcf346516a8875c6e0ca0675853b9d7cffee pmc_35056079.pdf d9aa18b433d7f9f846470f630b62a2c0572009a2cf84f6b3df72f829efae08c9 pmc_35056079.pdf Title: Enhanced Transdermal Delivery of Pranoprofen Using a Thermo-Reversible Hydrogel Loaded with Lipid Nanocarriers for the Treatment of Local Inflammation Subject: 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. Keywords: pranoprofen; thermo-reversible hydrogel; nanostructured lipid carriers; transdermal delivery; inflammation Author: María Rincón, Marcelle Silva-Abreu, Lupe Carolina Espinoza, Lilian Sosa, Ana Cristina Calpena, María J. Rodríguez-Lagunas and Helena Colom Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Dec 24 12:35:34 2021 CET ModDate: Fri Dec 24 12:40:17 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 18 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 26186893 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- NABLIW+URWPalladioL-Bold Type 1 Custom yes yes no 10 0 PPPUYR+URWPalladioL-Roma Type 1 Custom yes yes no 15 0 ZRTGCK+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 RGUFCP+CMSY10 Type 1 Builtin yes yes no 23 0 IBTYZX+VnURWPalladioL Type 1 Custom yes yes no 27 0 YWWVQQ+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 40 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 44 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 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Children: Item: Title: Composition and Physicochemical Characterization of the PF-NLCs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Physicochemical Characterization of the PF-NLCs-F127 Hydrogel Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Children: Item: Title: Appearance, pH Evaluation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Morphological Studies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Gelling Temperature Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Swelling, Degradation and Porosity Studies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Rheological Behaviour Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Extensibility (Spreadability) Destination: 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edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612679d6 Item: Title: Extensibility (Spreadability) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@11758f2a Item: Title: Stability Studies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@e720b71 Item: Title: In vitro Release Studies of PF-NLCs-F127 Hydrogel Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1b26f7b2 Item: Title: Ex Vivo Skin Permeation Study Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@491cc5c9 Item: Title: In Vitro Cytotoxicity Studies with the MTT Assay Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@74ad1f1f Item: Title: In Vivo Tolerance Study by Evaluating Biomechanical Properties of Human Skin Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6a1aab78 Item: Title: In Vivo Assay and Histological Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@462d5aee Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@69b0fd6f Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@757942a1 Info: Title: Enhanced Transdermal Delivery of Pranoprofen Using a Thermo-Reversible Hydrogel Loaded with Lipid Nanocarriers for the Treatment of Local Inflammation Author: María Rincón, Marcelle Silva-Abreu, Lupe Carolina Espinoza, Lilian Sosa, Ana Cristina Calpena, María J. Rodríguez-Lagunas and Helena Colom Subject: 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. 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