780e562afae03662caaadf6fb63bd6fb pmc_35057095.pdf 011f744104d3c9c8b5f0115a24c2f45faa202add pmc_35057095.pdf 804567aae63a50ef034aaa85fecc6302c4ada1716027edf5e7458c07faa6a81a pmc_35057095.pdf Title: DELOS Nanovesicles-Based Hydrogels: An Advanced Formulation for Topical Use Subject: Topical delivery has received great attention due to its localized drug delivery, its patient compliance, and its low risk for side effects. Recent developments have focused on studying new drug delivery systems as a strategy for addressing the challenges of current topical treatments. Here we describe the advances on an innovative drug delivery platform called DELOS nanovesicles for topical drug delivery. Previously, the production of DELOS nanovesicles demonstrated potentiality for the topical treatment of complex wounds, achieving well-tolerated liquid dispersions by this route. Here, research efforts have been focused on designing these nanocarriers with the best skin tolerability to be applied even to damaged skin, and on exploring the feasibility of adapting the colloidal dispersions to a more suitable dosage form for topical application. Accordingly, these drug delivery systems have been efficiently evolved to a hydrogel using MethocelTM K4M, presenting proper stability and rheological properties. Further, the integrity of these nanocarriers when being gellified has been confirmed by cryo-transmission electron microscopy and by Förster resonance energy transfer analysis with fluorescent-labeled DELOS nanovesicles, which is a crucial characterization not widely reported in the literature. Additionally, in vitro experiments have shown that recombinant human Epidermal Growth Factor (rhEGF) protein integrated into gellified DELOS nanovesicles exhibits an enhanced bioactivity compared to the liquid form. Therefore, these studies suggest that such a drug delivery system is maintained unaltered when hydrogellified, becoming the DELOS nanovesicles-based hydrogels, an advanced formulation for topical use. Keywords: nanovesicles; topical drug delivery; hydrogel; rheology; vesicle integrity Author: Lídia Ballell-Hosa, Elisabet González-Mira, Hector Santana, Judit Morla-Folch, Marc Moreno-Masip, Yaima Martínez-Prieto, Albert Revuelta, Primiano Pio Di Mauro, Jaume Veciana, Santi Sala, Lidia Ferrer-Tasies and Nora Ventosa Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Jan 18 04:18:30 2022 CET ModDate: Tue Jan 18 04:32:53 2022 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 19 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 19608710 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- OHKNFJ+VnURWPalladioL Type 1 Custom yes yes no 10 0 UZETBB+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 GJLULQ+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 ZHUUFJ+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 SSNIUI+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 36 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 40 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 44 0 IAFAOG+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 57 0 EFICKW+CMSY10 Type 1 Builtin yes yes no 88 0 NXQZWG+EURM10 Type 1 Builtin yes yes no 92 0 UFLZZD+CMEX10 Type 1 Builtin yes yes no 106 0 GIGFZE+CMR10 Type 1 Builtin yes yes no 110 0 TRMLHD+MSAM10 Type 1 Builtin yes yes no 173 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-05-07 04:34:59 CEST RepresentationInformation: pmc_35057095.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2022-01-31 03:35:24 CET Size: 19608710 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 419 FreeObjects: 17 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Materials Destination: subsection.2.1 Item: Title: Preparation of DELOS Nanovesicles Destination: subsection.2.2 Item: Title: Preparation of Hydrogels Enriched with DELOS Nanovesicles Destination: subsection.2.3 Item: Title: DELOS Nanovesicles and Hydrogels Characterization Destination: subsection.2.4 Children: Item: Title: Particle Size, Polydispersity Index and Zeta Potential Assessment Destination: subsubsection.2.4.1 Item: Title: Morphological Characterization by Cryo-Transmission Electron Microscopy (Cryo-TEM) Destination: subsubsection.2.4.2 Item: Title: Hydrogel Microscopical Appearance Destination: subsubsection.2.4.3 Item: Title: Hydrogel Rheological Properties Destination: subsubsection.2.4.4 Item: Title: Absorption and Fluorescence Spectroscopy Measurements of Dye-Labelled DELOS Nanovesicles Destination: subsubsection.2.4.5 Item: Title: Confocal Microscopic Characterization of Dye-Labelled DELOS Nanovesicles-Based Hydrogels Destination: subsubsection.2.4.6 Item: Title: In Vitro rhEGF Biological Activity by Cell Proliferation Assay Destination: subsubsection.2.4.7 Item: Title: Statistical Analysis Destination: subsection.2.5 Item: Title: Results and Discussion Destination: section.3 Children: Item: Title: Development of DELOS Nanovesicle Suspensions with Different Surfactant Counterions and Dispersant Media Preparation and Physicochemical Characterization Destination: subsection.3.1 Item: Title: Semi-Solid Dosage Form: Hydrogels Enriched with DELOS Nanovesicles Destination: subsection.3.2 Children: Item: Title: Preparation and Physicochemical Characterization of DELOS Nanovesicles-Based Hydrogels Destination: subsubsection.3.2.1 Item: Title: Integrity of DELOS Nanovesicles When Gellified Destination: subsubsection.3.2.2 Item: Title: In Vitro Protein-Specific Bioactivity of Gellified rhEGF-DELOS Nanovesicles Destination: subsubsection.3.2.3 Item: Title: Conclusions Destination: section.4 Item: Title: References Destination: section.4 Info: Title: DELOS Nanovesicles-Based Hydrogels: An Advanced Formulation for Topical Use Author: Lídia Ballell-Hosa, Elisabet González-Mira, Hector Santana, Judit Morla-Folch, Marc Moreno-Masip, Yaima Martínez-Prieto, Albert Revuelta, Primiano Pio Di Mauro, Jaume Veciana, Santi Sala, Lidia Ferrer-Tasies and Nora Ventosa Subject: Topical delivery has received great attention due to its localized drug delivery, its patient compliance, and its low risk for side effects. Recent developments have focused on studying new drug delivery systems as a strategy for addressing the challenges of current topical treatments. Here we describe the advances on an innovative drug delivery platform called DELOS nanovesicles for topical drug delivery. Previously, the production of DELOS nanovesicles demonstrated potentiality for the topical treatment of complex wounds, achieving well-tolerated liquid dispersions by this route. Here, research efforts have been focused on designing these nanocarriers with the best skin tolerability to be applied even to damaged skin, and on exploring the feasibility of adapting the colloidal dispersions to a more suitable dosage form for topical application. Accordingly, these drug delivery systems have been efficiently evolved to a hydrogel using MethocelTM K4M, presenting proper stability and rheological properties. Further, the integrity of these nanocarriers when being gellified has been confirmed by cryo-transmission electron microscopy and by Förster resonance energy transfer analysis with fluorescent-labeled DELOS nanovesicles, which is a crucial characterization not widely reported in the literature. Additionally, in vitro experiments have shown that recombinant human Epidermal Growth Factor (rhEGF) protein integrated into gellified DELOS nanovesicles exhibits an enhanced bioactivity compared to the liquid form. Therefore, these studies suggest that such a drug delivery system is maintained unaltered when hydrogellified, becoming the DELOS nanovesicles-based hydrogels, an advanced formulation for topical use. 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