title: Polymeric nanoparticles modified with fatty acids encapsulating betamethasone for anti-inflammatory treatment.
abstract: Topical glucocorticosteroids were incorporated into nanocarrier-based formulations, to overcome side effects of conventional formulations and to achieve maximum skin deposition. Nanoparticulate carriers have the potential to prolong the anti-inflammatory effect and provide higher local concentration of drugs, offering a better solution for treating dermatological conditions and improving patient compliance. Nanoparticles were formulated with poly-ϵ-caprolactone as the polymeric core along with stearic acid as the fatty acid, for incorporation of betamethasone-21-acetate. Oleic acid was applied as the coating fatty acid. Improvement of the drug efficacy, and reduction in drug degradation with time in the encapsulated form was examined, while administering it locally through controlled release. Nanoparticles were spherical with mean size of 300 nm and negatively charged surface. Encapsulation efficiency was 90%. Physicochemical stability in aqueous media of the empty and loaded nanoparticles was evaluated for six months. Drug degradation was reduced compared to free drug, after encapsulation into nanoparticles, avoiding the potency decline and promoting a controlled drug release over one month. Fourier transform infrared spectroscopy and thermal analysis confirmed drug entrapment, while cytotoxicity studies performed in vitro on human keratinocytes, Saccharomyces cerevisiae models and Artemia salina, showed a dose-response relationship for nanoparticles and free drug. In all models, drug loaded nanoparticles had a greater inhibitory effect. Nanoparticles increased drug permeation into lipid membranes in vitro. Preliminary safety and permeation studies conducted on rats, showed betamethasone-21-acetate in serum after 48 h application of a gel containing nanoparticles. No skin reactions were observed. In conclusion, the developed nanoparticles may be applied as topical treatment, after encapsulation of betamethasone-21-acetate, as nanoparticles promote prolonged drug release, increase drug stability in aqueous media, reducing drug degradation, and increase drug permeability through lipid membranes.
authors.affiliation: CBiOS, Research Center for Biosciences & Health Technologies, Universidade Lusófona, Campo Grande 376, 1749-024 Lisboa, Portugal; Department of Biomedical Sciences, Faculty of Pharmacy, University of Alcalá, Ctra. Universidad Complutense, 28871 Alcalá de Henares, Spain.
authors.forename: Catarina Oliveira
authors.initials: CO
authors.lastname: Silva
authors.affiliation: CBiOS, Research Center for Biosciences & Health Technologies, Universidade Lusófona, Campo Grande 376, 1749-024 Lisboa, Portugal; iMed.ULisboa, Instituto de Investigação do Medicamento, Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Rijo
authors.affiliation: Department of Biomedical Sciences, Faculty of Pharmacy, University of Alcalá, Ctra. Universidad Complutense, 28871 Alcalá de Henares, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Molpeceres
authors.affiliation: Pharmacology and Pharmaceutical Care, Faculty of Pharmacy, Universidade de Coimbra, Azinhaga de Santa Comba, 3000-354 Coimbra, Portugal; IBILI, Institute for Biomedical Imaging and Life Sciences, Universidade de Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
authors.forename: Isabel Vitória
authors.initials: IV
authors.lastname: Figueiredo
authors.affiliation: Centro de Estudos do Ambiente e do Mar (CESAM), Universidade de Lisboa, Faculdade de Ciências de Lisboa, CBV, Campo Grande, 1949-016 Lisboa, Portugal.
authors.forename: Lia
authors.initials: L
authors.lastname: Ascensão
authors.affiliation: CBiOS, Research Center for Biosciences & Health Technologies, Universidade Lusófona, Campo Grande 376, 1749-024 Lisboa, Portugal; iMed.ULisboa, Instituto de Investigação do Medicamento, Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Ana Sofia
authors.initials: AS
authors.lastname: Fernandes
authors.affiliation: CBiOS, Research Center for Biosciences & Health Technologies, Universidade Lusófona, Campo Grande 376, 1749-024 Lisboa, Portugal.
authors.forename: Amílcar
authors.initials: A
authors.lastname: Roberto
authors.affiliation: CBiOS, Research Center for Biosciences & Health Technologies, Universidade Lusófona, Campo Grande 376, 1749-024 Lisboa, Portugal; IBEB, Biophysics and Biomedical Engineering, Faculty of Sciences, Universidade de Lisboa, 1749-016, Lisboa, Portugal. Electronic address: catarina.reis@ulusofona.pt.
authors.forename: Catarina Pinto
authors.initials: CP
authors.lastname: Reis
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000279:Administration, Cutaneous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D001156:Artemia / Q000187:drug effects; D001623:Betamethasone / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D065546:Drug Liberation; D004355:Drug Stability; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D019301:Oleic Acid / Q000737:chemistry; D020442:Poloxamer / Q000737:chemistry; D017208:Rats, Wistar; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000254:growth & development; D012869:Skin Absorption
chemical_list: D000180:Acrylic Resins; D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D020442:Poloxamer; D019301:Oleic Acid; C006903:carbopol 940; D001623:Betamethasone
keywords: Betamethasone (PubChem CID: 9782); Betamethasone-21-acetate; Betamethasone-21-acetate (PubChem CID: 443.967); Chronic inflammation; Nanoparticles; Oleic acid; Oleic acid (PubChem CID: 445.639); Pluronic(®) F127 (PubChem CID: 24.751); Poly-Ɛ-caprolactone (PubChem CID: 10.401); Poly-ϵ-caprolactone; Stearic acid (PubChem CID: 5281); Transdermal drug delivery