title: Anti-Toxoplasma activity and impact evaluation of lyophilization, hot molding process, and gamma-irradiation techniques on CLH-PLGA intravitreal implants.
abstract: Intraocular delivery systems have been developed to treat many eye diseases, especially those affecting the posterior segment of the eye. However, ocular toxoplasmosis, the leading cause of infectious posterior uveitis in the world, still lacks an effective treatment. Therefore, our group developed an intravitreal polymeric implant to release clindamycin, a potent anti-Toxoplasma antibiotic. In this work, we used different techniques such as differential scanning calorimetry, thermogravimetry, X-ray diffraction, scanning electron microscopy, and fourier-transform infrared spectroscopy to investigate drug/polymer properties while manufacturing the delivery system. We showed that the lyophilization, hot molding process, and sterilization by gamma irradiation did not change drug/polymer physical-chemistry properties. The drug was found to be homogeneously dispersed into the poly lactic-co-glycolic acid (PLGA) chains and the profile release was characterized by an initial burst followed by prolonged release. The drug profile release was not modified after gamma irradiation and non-covalent interaction was found between the drug and the PLGA. We also observed the preservation of the drug activity by showing the potent anti-Toxoplasma effect of the implant, after 24-72 h in contact with cells infected by the parasite, which highlights this system as an alternative to treat toxoplasmic retinochoroiditis.
authors.affiliation: Faculty of Pharmacy of the Federal University of Minas Gerais, Av. Presidente Antônio Carlos, 6627, Belo Horizonte, MG, 31270-901, Brazil. gabriellafcunha@gmail.com.
authors.forename: Gabriella M
authors.initials: GM
authors.lastname: Fernandes-Cunha
authors.affiliation: Department of Biochemistry and Immunology Department, Institute of Biological Science of the Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Cíntia M F
authors.initials: CM
authors.lastname: Rezende
authors.affiliation: Chemistry Department of the Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Wagner N
authors.initials: WN
authors.lastname: Mussel
authors.affiliation: School of Pharmacy, Federal University of Sao Joao del-Rei, Divinópolis, MG, Bazil.
authors.forename: Gisele R
authors.initials: GR
authors.lastname: da Silva
authors.affiliation: Laboratory of Thermal Analysis, Chemistry Department of the Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Elionai C
authors.initials: EC
authors.lastname: de L Gomes
authors.affiliation: Laboratory of Thermal Analysis, Chemistry Department of the Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Yoshida
authors.affiliation: Ezequiel Dias Foundation, Belo Horizonte, MG, Brazil.
authors.forename: Sílvia L
authors.initials: SL
authors.lastname: Fialho
authors.affiliation: Department of Biochemistry and Immunology Department, Institute of Biological Science of the Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Alfredo M
authors.initials: AM
authors.lastname: Goes
authors.affiliation: Department of Biochemistry and Immunology Department, Institute of Biological Science of the Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Dawison A
authors.initials: DA
authors.lastname: Gomes
authors.affiliation: Department of Parasitology, Institute of Biological Science of the Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Ricardo W
authors.initials: RW
authors.lastname: de Almeida Vitor
authors.affiliation: Faculty of Pharmacy of the Federal University of Minas Gerais, Av. Presidente Antônio Carlos, 6627, Belo Horizonte, MG, 31270-901, Brazil.
authors.forename: Armando
authors.initials: A
authors.lastname: Silva-Cunha
mesh_terms: D000981:Antiprotozoal Agents / Q000008:administration & dosage*; D002152:Calorimetry, Differential Scanning; D002460:Cell Line; D002981:Clindamycin / Q000008:administration & dosage*; D005612:Freeze Drying; D005720:Gamma Rays; D006358:Hot Temperature; D006801:Humans; D019344:Lactic Acid; D008855:Microscopy, Electron, Scanning; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry; D014122:Toxoplasma / Q000187:drug effects*; D014822:Vitreous Body; D014961:X-Ray Diffraction
chemical_list: D000981:Antiprotozoal Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002981:Clindamycin