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The global rise in antimicrobial resistance has created an urgent demand for novel drug delivery strategies that can improve access to antibiotics and reduce reliance on intravenous administration. Oral therapy remains the most practical route for outpatient treatment, yet many antibiotics display poor solubility, low permeability, and instability in the gastrointestinal tract, limiting their effectiveness. Lipid-based nanocarriers, particularly liquid crystal nanoparticles (LCNPs), offer structural versatility, high internal surface area, and tunable release properties that make them attractive for enabling oral delivery. 

The overall aim of this thesis was to develop LCNP-based oral formulations of clinically relevant antibiotics through an integrated approach combining molecular understanding with potential scalable manufacturing.

In the first part, antibiotic-loaded LCNPs with internal cubic and hexagonal phases were developed from non-digestible lipid building blocks and systematically evaluated for their physicochemical properties, stability in simulated intestinal fluids, and impact on representative commensal bacteria. Complementing these experimental findings, all-atom molecular dynamics simulations were employed to reveal that the studied antibiotics, clarithromycin preferentially localized within the lipid domain, whereas vancomycin resided at the lipid–water interface. Therefore, these primary results provide both experimental and molecular-level evidence for how lipid composition and nanostructure govern drug localization, stability, and release in LCNPs-based antibiotic formulations.

In the second part, the influence of internal mesophase on transepithelial permeability was investigated in intestinal models using Caco-2 cells. Compared with liposomes, non-lamellar LCNPs exhibited superior uptake via energy-independent internalization and significantly enhanced vancomycin transport across intestinal monolayers, underscoring the role of mesophase architecture in promoting oral absorption.

In the final part, a semi-solid extrusion (SSE) 3D printing platform was developed to convert vancomycin-loaded hexosomes into personalized oral tablets. LCNPs-based formulations preserved a stable hexagonal phase throughout the preparation of the printable gel, the 3D printing process, and tablet rehydration. Moreover, the printed tablets complied with European Pharmacopoeia standards for mass uniformity, drug content, and disintegration. The optimized gels displayed favorable rheological properties, ensuring precise, reproducible dosing for better patient compliance.