Banca de DEFESA: ANDERSON FERREIRA SEPÚLVEDA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : ANDERSON FERREIRA SEPÚLVEDA
DATA : 01/07/2022
HORA: 09:00
LOCAL: Remoto
TÍTULO:

DEVELOPMENT OF POLOXAMER-HYALURONIC ACID THERMOSENSITIVE HYDROGELS: INFLUENCE OF SUPRAMOLECULAR STRUCTURE ON DRUGS RELEASE KINETICS

PÁGINAS: 165
GRANDE ÁREA: Ciências Biológicas
ÁREA: Biofísica
SUBÁREA: Biofísica de Processos e Sistemas
RESUMO:

Hydrogels have been used as materials for pharmaceutical and cosmetic purposes, due to their ability to control the release of the drug and its low toxicity, greatly reducing the frequency of drug application. These hydrogels are formed by triblock polymers responsive to temperature known as Poloxamer (PL), which in aqueous media, form micelles with a hydrophobic core and a hydrophilic corona, self-assembled according to the temperature, known as sol-gel transition state. This characteristic is what allows the incorporation of drugs, and as the gel is disintegrated, the drug is gradually released. This thesis intends to describe the physicochemical and mechanical characteristics of hydrogels formed by Poloxamer containing the local anesthetics bupivacaine (BVC) 0.5% and ropivacaine (RVC) 0.5%. PL 407 at 15% and 30% were used alone, or in a binary system with PL 338 (15% / 15%), combined or not with 0.5% hyaluronic acid (HA). The experimental methodology was based on scanning electron microscopy (SEM), dynamic light scattering (DLS), differential scattering calorimetry (DSC), rheology and small-angle neutron scattering (SANS) to explore micellar and material quality, in addition to their stability. Coarse-grained simulations were also performed to study the interaction among polymers. DLS measurements showed that the micelles do not have their dimensions very affected by the addition of HA or any of the drugs. However, the internal organization of the formulations is modified by hydrophobic interactions (caused by BVC or RVC) or by hydrophilic interactions (caused by PL 338 or HA), observed by changes in the entropy of the formulations and in the micellization temperature. These changes in structures reflect the organization of polymeric networks and elastic characteristics of the gel. The increase in interactions between the chains caused by the presence of BVC, more hydrophobic than RVC, promotes an increase in hydrogel stiffness mainly in formulations containing PL 407 30%, compared to formulations of PL 407 15% and PL 407 15% + PL 338 15%. SANS results confirm that all formulations containing PL 407 15% presented lamellar structures, as expected for low-concentrated hydrogels. For PL 407 30% and PL 407 15% + PL 338 15%, both cubic and hexagonal structures were identified, justifying material high consistency. Moreover, the addition of BVC, RVC or HA interfere in the structuring of supramolecular organizations by enhancing the interactions among components, except for PL 407 15% + PL 338 15% formulations. For these formulations, it is observed that the internal organization and the dimensions of the structures are not affected by the temperature or the addition of additive. As simulations showed, the binary systems are formed by micelles composed exclusively of PL 407 and PL 338 at 25 °C and 37 °C, which may reflect on the stability of the system. Both PL 407 30% and PL 407 15% + PL 338 15% presented similar patterns of drug release, but the addition of HA in the binary system proved to be more efficient to retain BVC or RVC.  In conclusion, this thesis intended to present various techniques that can inform about material characteristics of drug-delivery systems and to describe how molecular dynamics allows to study morphological organization and the role of each component.

MEMBROS DA BANCA:
Presidente - Interno ao Programa - 1675708 - DANIELE RIBEIRO DE ARAUJO
Membro Titular - Examinador(a) Interno ao Programa - 1563992 - ANA LIGIA BARBOUR SCOTT
Membro Titular - Examinador(a) Externo ao Programa - 1762438 - JEAN JACQUES BONVENT
Membro Titular - Examinador(a) Externo à Instituição - LUCIANA MAGALHAES REBELO ALENCAR - UFMA
Membro Titular - Examinador(a) Externo à Instituição - ADRIANA FONTES - UFPE
Membro Suplente - Examinador(a) Interno ao Programa - 2605490 - SERGIO DAISHI SASAKI
Membro Suplente - Examinador(a) Externo ao Programa - 1734908 - FABIO FURLAN FERREIRA
Membro Suplente - Examinador(a) Externo ao Programa - 1763495 - WANIUS JOSE GARCIA DA SILVA
Membro Suplente - Examinador(a) Externo à Instituição - LINDOMAR JOSE CALUMBY ALBUQUERQUE
Membro Suplente - Examinador(a) Externo à Instituição - PAULA SILVIA HADDAD FERREIRA - UNIFESP