The aim of the study was to develop a novel buccal dosage form to transport rhodamine 123 and human insulin as models for poorly water-soluble and biological drugs, using lipid-core micelles (LCMs)-loaded mucoadhesive films. LCMs were synthesized by a low-energy hot emulsification process, yielding spherically shaped, small-sized, monodispersed and negatively charged carriers with high entrapment efficiency. In vitro release studies demonstrated a higher release of insulin rather than rhodamine from LCMs in simulated physiological conditions, due to an initial burst release effect; however, both release profiles are mainly explained by a diffusion mechanism. Furthermore, LCMs-loaded mucoadhesive films were manufactured and preserved with similar mechanical properties and optimal mucoadhesive behavior compared to nonloaded films. Ex vivo permeation experiments using excised porcine buccal epithelium reveal that both rhodamine and insulin-loaded LCM films elicited a significantly enhanced permeation effect compared to LCMs in suspension and free drugs in solution as controls. Hence, LCMs-loaded mucoadhesive films are suitable as buccal dosage form for the transport and delivery of rhodamine 123 and insulin, as models for poorly water-soluble and biological drugs, respectively.

Context: In the north of Chile, the Atacama Desert and the town of Pica are located, where numerous fruits grow, including citrus ecotypes that generate waste such as the seeds of these fruits. Aims: To evaluate the influence of extraction methods on fatty acid composition, nutritional quality indexes of lipids, total phenolic content and antioxidant capacity of acid lime (AL) and sweet orange (SO) seed oils from Pica oasis. Methods: Extraction of these oils was performed using Soxhlet (SE) and direct (D-UAE) or indirect (I-UAE) ultrasound-assisted extraction techniques. Results: The highest oil yields were obtained using SE (AL = 31.90%, SO = 33.32%). These oils were found to be a rich source of unsaturated fatty acids. Linoleic (36.69%, SE), palmitic (21.90%, SE), oleic (18.07%, UAE-D), a-linolenic (11.45%, D-UAE), and myristoleic (5.91%, D-UAE) acids were the highest concentrations found in AL, while in SO they were oleic and a-linolenic acids (22.54 and 4.53%, respectively) in SE. Total phenolic contents were found without statistical differences between extraction methods (AL =0.719 – 0.787 mg GAE/g oil and SO = 0.653 – 0.915 mg GAE/g oil), except D-UAE SO (0.653 mg GAE/g oil). These oils had similar radical scavenging capacity and reducing power, except in ORAC method (41.99 vs. 96.39 µmol TE/g oil for AL and SO, respectively both in SE). The indexes of nutritional quality were similar among the different methods for the same species, but some of them presented statistically significant differences between the species. Conclusions: An influence of extraction methods on fatty acid composition, total phenolic content and antioxidant capacity of AL and SO seed oils with better results achieved using SE followed by I-UAE was demonstrated. This work establishes the potential source of nutritional compounds of these seeds that grow in the Atacama Desert, Chile.

Esta tesis está vinculada con el área de la farmacognosia y el estrés oxidativo. Los conocimientos sobre los aceites presentes en las semillas de diferentes frutos sirvieron de base para que en el Laboratorio de Productos Naturales del Departamento de Ciencias Farmacéuticas de la Universidad Católica del Norte se extrajeran aceites de semillas de Citrus aurantifolia (Christm.) Swingle (limón de Pica) y Citrus sinensis (L.) Osbeck (naranja dulce de Pica). Para ello, se utilizaron las técnicas de extracción por Soxhlet, ultrasonido directo y ultrasonido indirecto, obteniéndose un mayor rendimiento con el primer método. Además, fue determinado el perfil de ácidos grasos, con composición mayoritaria de ácidos grasos insaturados, como los ácidos linoleico y oleico. También, se determinaron la cantidad de fenoles totales presentes y la actividad antioxidante, obteniendo mejores resultados para los aceites derivados de las semillas de naranja dulce de Pica. La tesis está constituida por 131 páginas y su estructura comprende una introducción, cuatro capítulos, referencias bibliográficas y otras informaciones (anexos).