title: A Quality by design (QbD) approach on starch-based nanocapsules: A promising platform for topical drug delivery.
abstract: Exploring novel applications for approved excipients with a history of safe use in therapeutics is a smart strategy to obtain improved pharmaceutical products. The present study aimed at developing a novel starch-based nanoparticulate carrier system (StNC) for topical delivery of lipophilic bioactive molecules. The role of the different factors that affect the particle size distribution and zeta potential of StNC prepared by the emulsification-solvent evaporation method was assessed using a quality by design approach. An optimal formulation was selected and fully characterized in terms of molecular interactions (DSC and FTIR), morphology (TEM and AFM), as well as in vitro and in vivo biological properties, including biological sensitivity/irritation studies performed in human volunteers. Results show the surfactant and lipid contents play a major role in StNC particle size distribution. In addition, all tested formulations presented a zeta potential of ca. +33.6±6.7 mV, indicating a good physical stability, while revealing an excellent compromise between stability, safety and cosmeticity, evidencing that StNC are suitable nanocarriers for topical use. Finally, the design planning methodology has clearly shown its usefulness for optimizing the formulation, being also crucial for the understanding of StNC formation process. The StNC proved to be a promising formulation strategy and a potential nanocarrier for topical lipophilic bioactive molecules.
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Marto
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal.
authors.forename: L F
authors.initials: LF
authors.lastname: Gouveia
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal.
authors.forename: L M
authors.initials: LM
authors.lastname: Gonçalves
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal.
authors.forename: D P
authors.initials: DP
authors.lastname: Gaspar
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal.
authors.forename: P
authors.initials: P
authors.lastname: Pinto
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: F A
authors.initials: FA
authors.lastname: Carvalho
authors.affiliation: Laboratórios Atral S.A., Vala do Carregado, Portugal.
authors.forename: E
authors.initials: E
authors.lastname: Oliveira
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal.
authors.forename: H M
authors.initials: HM
authors.lastname: Ribeiro
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal. Electronic address: aalmeida@ff.ulisboa.pt.
authors.forename: A J
authors.initials: AJ
authors.lastname: Almeida
mesh_terms: D000287:Administration, Topical; D002152:Calorimetry, Differential Scanning; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D010328:Patch Tests / Q000379:methods; D017550:Spectroscopy, Fourier Transform Infrared; D013213:Starch / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D008055:Lipids; D053769:Nanocapsules; D013501:Surface-Active Agents; D013213:Starch
keywords: Nanocapsules; Quality by design; Skin; Starch; Topical application