BIomimetic Shell Engineering of Microvehicles for Encapsulation of Bioactive Compounds

Abstract

Biomimicry is the study of nature and natural phenomena to understand the principles of underlying mechanisms, to obtain ideas from nature, and to apply concepts that may benefit science, engineering, and medicine. Biomimicry is centered on the idea that there is no model better than nature for developing something new and has produced excellent results in productivity and function. Examples of biomimetic studies include fluid-drag reduction swimsuits inspired by the structure of shark’s skin, velcro fastener modeled on burrs, shape of airplanes developed from the look of birds, and stable building structures copied from the backbone of honeycomb. A main biomimetic biological structures is to protect the inner fruit - in particular the seeds against various environmental influences including UV radiation, water loss or mechanical damage caused by impact on the ground when the ripe fruits or seeds are shed or by animals trying to eat the seeds. Their excellent protective properties make fruit walls highly interesting as role models for the development of puncture- and impact resistant materials and components. Therefore, when a new microcapsule is developed that meets all of the above requirements, my major concern is expected that the development of a new drug carrier and drug delivery technology In chapter 2, we introduces a new type of uniform liposome-analogous vesicle with a highly stable shell structure in which water-in-oil-in-water double emulsion drops fabricated in a capillary-based microfluidic device are used as templates. The vesicles developed in this work consist of a poly(ethylene glycol) hydrogel core surrounded by a polyurethane (PU) film between 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) layers. Subjecting the double emulsion templates to UV irradiation leads to the formation of a PU elastomer film between the DPPC layers. The presence of a thin PU film sandwiched between the DPPC layers was confirmed by confocal laser microscopy. The thicknesses of the PU films were measured to be approximately ~4 m. Further study revealed the incorporation of the PU film between the DPPC layers remarkably improves the shell impermeability. Our vesicle system is expected to be useful for regulating the permeation of small molecules through lipid-based vesicular films. In chapter 3, we introduce a robust and straightforward approach to fabricate structurally stable GUVs (giant unilamellar vesicles) of which DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) bilayer membrane was made rigid by the introduction of amphiphilic block polymers. In particular, we figured out that the lateral co-assembly of an amphiphilic triblock copolymer with an aliphatic middle block and a sufficiently long molecular weight (20K g/mol) remarkably enhanced the compressive membrane modulus (Kexp) of GUVs. When the membrane composition was optimized, the Kexp of polymer-hybridized GUVs increased to 60 MPa, which approximately 20 times higher than that of DPPC GUVs, thus leading to a much longer half-life. In chapter 4. the surface of the most fruits is covered with a peel that provides protection against dehydration and nutrient oxidation. For biomimicry of the structure and function of fruit peels, we coated gelatin hydrogel microcapsules with alternate biocelluose layers consisting of a cuticle and several biocellulose layers containing wax and phenolic compounds. Dodecane nanodrops of which interface was stabilized by poly(ethylene oxide)-block-poly(-caprolactone) copolymer (PEO-b-PCL) and lecithin were incorporated into the outermost cuticle layer. We observed the presence of dodecane nanodrops in the cuticle layer softened the layer, thus preventing generation of microcracks, which is essential for minimizing dehydration in the process of drying. We also incorporate a phenolic compound, gallic acid, which is encapsulated in the micelles of PEO-b-PCL and lecithin, into the epidermis layer. Gallic acid in the mesocarp exhibit antioxidation performance against influx of oxygen that generates free radical intermediates. Finally, we demonstrated that biomimetic fabrication of the mechanically reinforced shell enhanced encapsulation of antioxidants as well as oxygen attack from the surroundings.