Submitted by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-09-22T17:48:51Z No. of bitstreams: 1 TES_RODRIGO_SCOPEL_COMPLETO.pdf: 15566888 bytes, checksum: 14d33da014482ed0a63266b36e2baee6 (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-09-22T17:49:44Z (GMT) No. of bitstreams: 1 TES_RODRIGO_SCOPEL_COMPLETO.pdf: 15566888 bytes, checksum: 14d33da014482ed0a63266b36e2baee6 (MD5) / Made available in DSpace on 2017-09-22T17:49:54Z (GMT). No. of bitstreams: 1 TES_RODRIGO_SCOPEL_COMPLETO.pdf: 15566888 bytes, checksum: 14d33da014482ed0a63266b36e2baee6 (MD5) 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.