Development Of Solid Lipid Polymer Hybrid Nanoparticles As Potential Oral Delivery Systems For Lipophilic Bioactive Compounds

Solid lipid-polymer hybrid nanoparticles (SLPN) are nanocarriers made from a combination of polymers and lipids. By integrating the advantages of biocompatible lipid-based nanoparticles and gastrointestinal (GI)-stable polymeric nanoparticles, SLPN are the ideal delivery system for delivering lipophilic compounds orally. In this project, two novel preparation strategies were proposed to fabricate GI-stable SLPN: 1) Bovine serum albumin (BSA) and dextran were first conjugated through Maillard reaction and the conjugates were exploited as macromolecular emulsifier and surface coating layer to prepare SLPN by a solvent diffusion and sonication method. In this approach, the multilayer structure was formed by self-assembly of BSA-dextran micelles to envelope solid lipid via a pH- and heating-induced facile process with simultaneous surface deposition of pectin; 2) Dextran was first oxidized and functionalized with more surface aldehyde groups, and then the SLPN was fabricated through in situ conjugation between oxidized dextran and BSA-emulsified solid lipid. Both types of SLPN were applied to encapsulate lipophilic bioactive compounds, including curcumin and astaxanthin (ASTN). The major objectives of this dissertation were to 1) systematically study the fabrication parameters in two preparation strategies to prepare SLPN; 2) comprehensively characterize the structural and colloidal properties of as-prepared two types of SLPN; 3) explore and compare the encapsulation and delivery applications of SLPN for lipophilic bioactive compounds, including curcumin and ASTN. In summary, the surface-functionalized SLPN could significantly improve the physicochemical properties of lipid nanoparticles and expand their potential as oral delivery systems for lipophilic bioactive compounds.