Banca de DEFESA: KELLI CRISTINA FREITAS MARIANO
Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.DISCENTE : KELLI CRISTINA FREITAS MARIANO
DATA : 21/12/2020
HORA: 09:00
LOCAL: UFABC-Campus Santo André
TÍTULO:
Lipidic and polymeric colloidal systems as drug nanocarriers for post-operative pain.
PÁGINAS: 100
GRANDE ÁREA: Ciências Biológicas
ÁREA: Farmacologia
SUBÁREA: Farmacologia Bioquímica e Molecular
RESUMO:
In postoperative pain therapy, we have local anesthetics (LA) and non-steroidal anti-inflammatory drugs (NSAIDs) as the main drugs used. Administered alone or in combination, they seek to increase the anesthetic / analgesic effect, being able to block excitation and/or conduction in peripheral nerves, as well as to reduce inflammatory mediators due to the operative process. They have a relatively short time of action and toxicity to the central nervous and cardiovascular system, being one of the biggest challenges and limitations in therapies. In this work, two drugs with different properties are analyzed: ibuprofen (IBF), a NSAID also used as an analgesic and antipyretic; and ropivacaine (RVC), a local anesthetic widely used in surgical procedures. The development of drug delivery systems for these drugs, seeking to prolong their half-life, dose and systemic toxicity through new formulations for the release of RVC and IBF through nanostructured carriers, are alternatives of wide interest. In this context, this work aims to: i) Develop a system for controlled release of RVC through hydrogels based on poloxamers 407 and 338 with different values of hydrophilic-lipophilic balance and characterize these new formulations; and ii) Develop a controlled release system for IBF encapsulated in solid lipid nanoparticles (NLS) and dispersed in PL407 and 338 thermoreversible hydrogels. An incorporation of RVC into hydrogels was 0.5% (m/v), and IBF to NLS was 1% (m/V). Rheological analyzes determined that the elastic (G′) and viscous (G″) modules, viscosity (η) and sol-gel (Tsolgel), presented higher values for G′ when compared to G″ (~ 40x) for RVC, and for IBF was G'>G ” in ~15 to 28 times, revealing viscoelastic character for both formulations, with Tsol-gel differences observed. Analysis of hydrodynamic light scattering (DLS) at 25ºC separation with bimodal distribution where PL 407 presented micellar diameter of 37.4 ± 0.3 nm and a smaller population of ~5 nm. Under 37°C, a unimodal distribution with smaller hydrodynamic diameters (21.71 ± 0.74 and 30.4 ± 3.5 nm) was observed for RVC, and for NLS diameters between ~272 to 389 nm, even with an incorporation of IBF. SEM (scanning electron microscopy) analyzes showed RVC with elongated, sharp and rectangular morphology. PL407 has a layered morphology while PL338 has a porous structure, with homogeneous characteristics even after the incorporation of RVC. These characteristics are confirmed in the analysis by AFM and observes NLS with rounded morphology and homogeneity after incorporation of IBF. The PL407/338 systems prolonged the release of RVC in vitro by ~4x when compared to free RVC in the 24h period and followed the mathematical release model proposed by Higuchi (0,92> R2> 0,98). The in vitro releasing of IBF inserted in the NLS and dispersed in PL407/338 had a reduction in the release time by ~10 times in the period of 24 hours compared to the free drug, following the Higuchi model (0,85> R2> 0,92). The NLS formulations were observed for 180 days and kept a stable behavior under a temperature of 4ºC. The results obtained contribute to the investigation and characterization of sustained release carriers for both ropivacaine, which has as a limitation of use its short action time, and for ibuprofen, which also presents in the formulations currently available a short time of action and gastrointestinal toxicity when administered orally. The nanostructured carrier systems developed demonstrated regulation of the release kinetics of these drugs in postoperative pain treatments, opening perspectives that justify clinical use.
MEMBROS DA BANCA:
Presidente - Interno ao Programa - 1675708 - DANIELE RIBEIRO DE ARAUJO
Membro Titular - Examinador(a) Interno ao Programa - 2605490 - SERGIO DAISHI SASAKI
Membro Titular - Examinador(a) Externo ao Programa - 1676364 - JULIANA MARCHI
Membro Titular - Examinador(a) Externo ao Programa - 1764675 - CHRISTIANE BERTACHINI LOMBELLO
Membro Titular - Examinador(a) Externo à Instituição - Juliana Mora Veridiano - MEDICINA ABC
Membro Suplente - Examinador(a) Interno ao Programa - 1640121 - LUCIANA CAMPOS PAULINO
Membro Suplente - Examinador(a) Externo à Instituição - CÍNTIA MARIA SAIA CEREDA