title: Development of hydrophilic nanocarriers for the charged form of the local anesthetic articaine.
abstract: One of the current challenges in drug encapsulation concerns the development of carrier systems for hydrophilic compounds. Potential carriers include nanocapsules prepared with amphiphilic polymers, which consist of a polymeric coating surrounding an aqueous nucleus, or dense matrices such as nanospheres of alginate/chitosan, where the drug may be dispersed in the matrix or adsorbed on the surface. The development of new formulations of nanocarriers, for example the poly(ethylene glycol)-poly(ɛ-caprolactone) (PEG-PCL) nanocapsules and alginate/chitosan (AG/CS) nanospheres described in this work, is needed in the case of ionized drugs such as articaine. This amino amide local anesthetic is the drug of choice in dentistry for regional anesthesia as well as the relief of acute and chronic pain. Here, the physico-chemical properties of suspensions of the nanoparticles (considering diameter, polydispersion, and zeta potential) were determined as a function of time, in order to establish the stability of the systems. The formulations did not show any substantial changes in these parameters, and were stable for up to 120 days of storage at ambient temperature. Satisfactory encapsulation efficiencies were obtained for the PEG-PCL nanocapsules (60%) and the AG/CS nanospheres (45%). Cytotoxicity assays confirmed that the encapsulation of articaine reduced its toxicity, relative to the free drug. The most promising results were obtained using the vesicular system (PEG-PCL nanocapsules), which not only altered the release profile of the drug, but also resulted in the lowest toxicity. This carrier system therefore holds promise for use in future practical applications.
authors.affiliation: Department of Environmental Engineering, São Paulo State University, Sorocaba, SP, Brazil; Department of Biochemistry, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Nathalie Ferreira
authors.initials: NF
authors.lastname: Silva de Melo
authors.affiliation: Department of Environmental Engineering, São Paulo State University, Sorocaba, SP, Brazil; Department of Biochemistry, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Estefânia Vangelie Ramos
authors.initials: EV
authors.lastname: Campos
authors.affiliation: Department of Biochemistry, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Camila Morais
authors.initials: CM
authors.lastname: Gonçalves
authors.affiliation: Department of Biochemistry, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Eneida
authors.initials: E
authors.lastname: de Paula
authors.affiliation: Department of Biotechnology, University of Sorocaba, Sorocaba, SP, Brazil.
authors.forename: Tatiane
authors.initials: T
authors.lastname: Pasquoto
authors.affiliation: Department of Biotechnology, University of Sorocaba, Sorocaba, SP, Brazil; São Carlos Federal University, Sorocaba, SP, Brazil.
authors.forename: Renata
authors.initials: R
authors.lastname: de Lima
authors.affiliation: Department of Environmental Engineering, São Paulo State University, Sorocaba, SP, Brazil.
authors.forename: André Henrique
authors.initials: AH
authors.lastname: Rosa
authors.affiliation: Department of Environmental Engineering, São Paulo State University, Sorocaba, SP, Brazil; Department of Biochemistry, State University of Campinas, Campinas, SP, Brazil. Electronic address: leonardo@sorocaba.unesp.br.
authors.forename: Leonardo Fernandes
authors.initials: LF
authors.lastname: Fraceto
mesh_terms: D016475:3T3 Cells; D000464:Alginates / Q000737:chemistry; D000779:Anesthetics, Local / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D002152:Calorimetry, Differential Scanning; D002355:Carticaine / Q000737:chemistry* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D010539:Permeability; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D055672:Static Electricity
chemical_list: D000464:Alginates; D000779:Anesthetics, Local; D004337:Drug Carriers; D006603:Hexuronic Acids; D011091:Polyesters; C016240:polycaprolactone; D011092:Polyethylene Glycols; D020723:Glucuronic Acid; D048271:Chitosan; D002355:Carticaine
keywords: Alginate/chitosan; Articaine; Local anesthetic; PEG–PCL copolymer; Polymeric nanoparticles