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.

Ocular safety of Intravitreal Clindamycin Hydrochloride Released by PLGA Implants

“…In order to provide more detailed knowledge about the potential ocular toxicity of clindamycin, in the present study, we evaluated the in vitro toxicity on retinal cells and in vivo drug toxicity in rat eyes usingin vivoretinal morphological test by optical coherence tomography, as well as ex vivo analyses by histology, immunofluorescence, and real-time PCR. This study, combined with previous reports of the drug anti-parasite activity (15) highlights clindamycin as an alternative treatment for ocular toxoplasmosis.…”

“…The implants were developed according to the technique previously described (14)(15)(16). CLH (Sigma-Aldrich Co. -St. Louis, MO, USA) and PLGA (50:50 Resomer® RG 503 inherent viscosity midpoint of 0.32-0.44 dl/g -EVONIK, Germany) were dissolved in a mixture of distilled water and acetonitrile and then lyophilized.…”

“…In previous studies, we have shown that clindamycin hydrochloride (CLH) released by poly(lactic-co-glycolic acid) (PLGA) implants did not cause inflammatory response by clinical evaluation of rabbit eyes, and did not decrease the ARPE-19 cell metabolic activity (14,15). In order to provide more detailed knowledge about the potential ocular toxicity of clindamycin, in the present study, we evaluated the in vitro toxicity on retinal cells and in vivo drug toxicity in rat eyes usingin vivoretinal morphological test by optical coherence tomography, as well as ex vivo analyses by histology, immunofluorescence, and real-time PCR.…”

Rosmarinic Acid Intravitreal Implants: A New Therapeutic Approach for Ocular Neovascularization

“…After incubation, pores and channels were observed, probably due to polymer degradation that involves breaking ester bonds of the PLGA chain by hydrolytic attack of water molecules of the media [26]. This facilitates drug release by diffusion throughout the polymeric matrix [27,28]. Rosmarinic acid is a small compound with slight solubility in water (1.3 g/L; 3.6 × 10 −3 mol/L).…”

Drug Micro-Carriers Based on Polymers and Their Sterilization

“…As mentioned earlier, the application of γirradiation to polymers can generate the polymer chain scission or crosslink. These effects produce different changes in morphology and size distribution of microparticles as well as in the drug release rate [40,309,[316][317][318]. Moreover, the results are dependent on the chemical structure of the active species (drug), presenting particularities on expected changes and the encapsulation efficiency of the drug.…”