title: Molecular modeling and cytotoxicity of diffractaic acid: HP-β-CD inclusion complex encapsulated in microspheres.
abstract: In this pioneer study, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was used to improve the solubility of the diffractaic acid (DA) via inclusion complex (DA:HP-β-CD). Subsequently, DA:HP-β-CD was incorporated into poly-ε-caprolactone (PCL) microspheres (DA:HP-β-CD-MS). Microspheres containing DA (DA-MS) or DA:HP-β-CD (DA:HP-β-CD-MS) were prepared using the multiple W/O/W emulsion-solvent evaporation technique. The phase-solubility diagram of DA in HP-β-CD (10-50mM) showed an ALtype curve with a stability constant K1:1=821M-1.1H NMR, FTIR, X-ray diffraction and thermal analysis showed changes in the molecular environment of DA in DA:HP-β-CD. The molecular modeling approach suggests a guest-host complex formation between the carboxylic moiety of both DA and the host (HP-β-CD). The mean particle size of the microspheres were ∅DA-MS=5.23±1.65μm and ∅DA:HP-β-CD-MS=4.11±1.39μm, respectively. The zeta potential values of the microspheres were ζDA-MS=-7.85±0.32mV and ζDA:HP-β-CD-MS=-6.93±0.46mV. Moreover, the encapsulation of DA:HP-β-CD into microspheres resulted in a more slower release (k2=0.042±0.001; r2=0.996) when compared with DA-MS (k2=0.183±0.005; r2=0.996). The encapsulation of DA or DA:HP-β-CD into microspheres reduced the cytotoxicity of DA (IC50=43.29μM) against Vero cells (IC50of DA-MS=108.48μM and IC50of DA:HP-β-CD-MS=142.63μM).
authors.affiliation: Centro Acadêmico de Vitória, Universidade Federal de Pernambuco (UFPE), Vitória de Santo Antão, PE, Brazil; Laboratório de Imunopatologia Keizo-Asami (LIKA), UFPE, Recife, PE, Brazil.
authors.forename: Camilla V N S
authors.initials: CV
authors.lastname: Silva
authors.affiliation: Laboratório de Imunopatologia Keizo-Asami (LIKA), UFPE, Recife, PE, Brazil.
authors.forename: Jéssica A P
authors.initials: JA
authors.lastname: Barbosa
authors.affiliation: Laboratório de Imunopatologia Keizo-Asami (LIKA), UFPE, Recife, PE, Brazil.
authors.forename: Milena S
authors.initials: MS
authors.lastname: Ferraz
authors.affiliation: Departamento de Bioquímica, UFPE, Recife, PE, Brazil.
authors.forename: Nicácio H
authors.initials: NH
authors.lastname: Silva
authors.affiliation: Departamento de Química, Universidade Federal de Mato Grosso do Sul (UFMS), Cuiabá, MS, Brazil.
authors.forename: Neli K
authors.initials: NK
authors.lastname: Honda
authors.affiliation: Laboratório de Química Teórica Medicinal, UFPE, Recife, PE, Brazil.
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Rabello
authors.affiliation: Laboratório de Química Teórica Medicinal, UFPE, Recife, PE, Brazil.
authors.forename: Marcelo Z
authors.initials: MZ
authors.lastname: Hernandes
authors.affiliation: Departamento de Física, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
authors.forename: Beatriz P
authors.initials: BP
authors.lastname: Bezerra
authors.affiliation: Centro Acadêmico de Vitória, Universidade Federal de Pernambuco (UFPE), Vitória de Santo Antão, PE, Brazil; Laboratório de Imunopatologia Keizo-Asami (LIKA), UFPE, Recife, PE, Brazil.
authors.forename: Isabella M F
authors.initials: IM
authors.lastname: Cavalcanti
authors.affiliation: Departamento de Física, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
authors.forename: Alejandro P
authors.initials: AP
authors.lastname: Ayala
authors.affiliation: Centro Acadêmico de Vitória, Universidade Federal de Pernambuco (UFPE), Vitória de Santo Antão, PE, Brazil; Laboratório de Imunopatologia Keizo-Asami (LIKA), UFPE, Recife, PE, Brazil.
authors.forename: Noemia P S
authors.initials: NP
authors.lastname: Santos
authors.affiliation: Laboratório de Imunopatologia Keizo-Asami (LIKA), UFPE, Recife, PE, Brazil. Electronic address: nssm@ufpe.br.
authors.forename: Nereide S
authors.initials: NS
authors.lastname: Santos-Magalhães
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D000840:Anisoles / Q000737:chemistry / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D016923:Cell Death / Q000187:drug effects; D002522:Chlorocebus aethiops; D006863:Hydrogen-Ion Concentration; D062385:Hydroxybenzoates / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D008958:Models, Molecular; D008968:Molecular Conformation; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011208:Powders; D066244:Proton Magnetic Resonance Spectroscopy; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D013818:Thermogravimetry; D014709:Vero Cells; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000840:Anisoles; D062385:Hydroxybenzoates; D011091:Polyesters; D011208:Powders; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C016240:polycaprolactone; C093528:diffractaic acid
keywords: Cyclodextrin; Diffractaic acid; Microspheres