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Previous issue date: 2017-03-29 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Human skin is an attractive option for applying active compounds that
minimize adverse effects due to low systemic exposure when compared with other
routes of administration. These compounds can permeate the skin layer by the
intercellular, intracellular and follicular routes resulting in a topical and/or transdermal
delivery. The delivery of active compounds via nanotechnology-based systems may
revolutionize the treatment of several disorders including the ones related with the
skin. Among these systems, liposomes, and biocompatible and bioabsorbable
polymeric nanoparticles, are the technologies with the greatest growth in the field.
Therefore, it is ideal to look for mechanisms that couple the mechanical advantages
of polymeric nanoparticles with the biomimetic characteristics of liposomes. The aim
of this work is to study the synthesis and behavior of hybrid nanoparticles comprising
a polymeric core (PLGA) coated by a mixture of lipids (HSPC:CHOL:DSPE-PEG)
functionalized to ligand molecules. Initially, it is proposed the conjugation of vitamin D
on the surface of the hybrid nanoparticles to target them for specific receptors (VDR)
present on melanocytes and melanoma cells. Subsequently, the synthesis of a RGD
peptide is carried out aiming to verify the possibility of applying the same
methodology for targeting more specific receptors of these cells. Seeking a greater
understanding about how the drug is released from these nanoparticles, in vitro
experiments of drug release are conducted. In addition, an explicit analytical solution
of the mathematical model proposed by Baker-Lonsdale is proposed in order to
obtain information regarding the transport phenomena that controls the drug release.
Finally, it is proposed a skin permeation mathematical model with boundary
conditions adapted for the target nanoparticles. / A pele ? uma rota de entrega atrativa para a aplica??o de f?rmacos que
minimiza efeitos adversos devido ? baixa exposi??o sist?mica quando comparada a
outras vias de aplica??o. Estes compostos podem permear a camada pelas rotas
intercelular, intracelular e transap?ndice resultando em uma entrega t?pica e/ou
transd?rmica. A entrega de compostos atrav?s de sistemas baseados na
nanotecnologia pode revolucionar o tratamento de diversas doen?as e disfun??es
onde, entre estes sistemas de libera??o, lipossomas e nanopart?culas polim?ricas
biocompat?veis, s?o as tecnologias que apresentam maior crescimento. A partir
disso, torna-se ideal a pesquisa de mecanismos que contemplem as vantagens
mec?nicas das nanopart?culas polim?ricas com as caracter?sticas biomim?ticas dos
lipossomas. O objetivo deste trabalho ? estudar a s?ntese e comportamento frente ?
aplica??o t?pica de nanopart?culas h?bridas compostas por um n?cleo de PLGA e
revestidas com uma mistura de fosfolip?dios (HSPC:COL:DSPE-PEG) funcionalizada
com mol?culas ligantes. Inicialmente, prop?e-se a conjuga??o de vitamina D na
superf?cie das nanopart?culas h?bridas com o objetivo de direcionar as mesmas para
receptores espec?ficos de vitamina D (VDR) presentes em melan?citos e c?lulas de
melanoma. Em sequ?ncia, a s?ntese do pept?deo RGD ? realizada verificando a
aplicabilidade da metodologia para um futuro direcionamento a receptores mais
espec?ficos presentes nestas c?lulas. Visando um maior entendimento sobre o
comportamento de libera??o de f?rmacos a partir destas nanopart?culas, testes in
vitro de libera??o s?o conduzidos. Al?m disso, ? sugerida uma solu??o anal?tica
expl?cita do modelo matem?tico de libera??o proposto por Baker-Lonsdale com o
objetivo de obter informa??es referentes ao fen?meno de transporte controlador do
processo de libera??o de f?rmacos. Por fim, prop?e-se um modelo matem?tico de
permea??o cut?nea com condi??es de contorno adequadas para estes
nanocarreadores.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/7659 |
| Date | 29 March 2017 |
| Creators | Silva, Rodrigo Scopel |
| Contributors | Vargas, Rubem M?rio Figueir? |
| Publisher | Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Programa de P?s-Gradua??o em Engenharia e Tecnologia de Materiais, PUCRS, Brasil, Faculdade de Engenharia |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS, instname:Pontifícia Universidade Católica do Rio Grande do Sul, instacron:PUC_RS |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | -7432719344215120122, 500, 500, 500, 600, -655770572761439785, 4518971056484826825, 2075167498588264571 |
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