Emulsion technology for the development of novel Alginate-based composite materials for controlled drug delivery applications

Emulsions have been used for centuries in many fields, such as pharmaceutical, cosmetic, food, and agriculture industry. Manufacturers of pharmaceutical products have recently shown great attention for multifunctional products in which different active agents can be incorporated, and for controlled drug delivery systems. Emulsion technology is a very simple, inexpensive and easy-to-scale approach. This technique is characterized by high loading capacity and encapsulation efficiency for therapeutic agents, independently from their nature (hydrophobic or hydrophilic). On the other hand, the other advantage is related to the possibility to use emulsion technology, to combine materials with different physiochemical properties. The aim of my doctoral research was focused on the development of new polymeric Alginate-based composite materials for biomedical applications, specifically, controlled delivery systems for drugs or bioactive molecules. The idea was to use biocompatible and non-toxic polymers, both of synthetic and natural origin, to produce the above-mentioned constructs. Biopolymers are widely used as scaffolds for biomedical applications, especially in tissue engineering and drug delivery systems due to their excellent properties such as biocompatibility, biodegradability to non-toxic products and bioactivity. In these fields, the biopolymers have been processed in different forms such as films, sponges, beads, hydrogels and capsules. However, emulsions containing dissolved biopolymers both in the oil and water phases are very scarce. In this thesis, we demonstrate such an emulsion, in which the oil phase contains a hydrophobic biodegradable polymeric material and the water phase is constituted by a sodium alginate solution. Emulsion technology was the main technique employed for the fabrication of composite matrices, constituted of hydrophilic and hydrophobic polymers, and for the encapsulation of model drugs (single and dual delivery of hydrophilic and hydrophobic active principles). Low cost raw materials and facile methods of fabrication were considered, in order to contain the costs of production, and obtain functional bio-composites easily scalable in an industrial setting. More detailed description about emulsions will be discussed in Chapter 1. In the first part of the thesis, as will be discussed in Chapter 2, we used an emulsion solution casting process to fabricate sodium alginate-Mater-Bi® polymer films that can retain both hydrophilic (a cutaneous antiseptic) and lipophilic (curcumin) model drugs. The objective was to achieve a biodegradable and biocompatible material as active dressing to promote and accelerate skin wound healing. The obtained matrices have been characterized in terms of their physio-chemical properties and their ability to release these model drugs individually or simultaneously in vitro. The novelty in this research was to demonstrate, for the first time the possibility to use Mater-Bi® also in the biomedical field. In fact, this commercial hydrophobic biodegradable polymer composite comprising polycaprolactone (PCL) and thermoplastic starch, obtained by a proprietary compound extrusion method is actively marketed as sustainable food packaging material as well as biodegradable material for perishable food containers. In the second part of the thesis, as will be discussed in Chapter 3, calcium alginate-Beeswax microbeads have been fabricated by a solvent free emulsion gelation technique. The objective of this study was to formulate an all-natural oral-controlled delivery system for a natural hydrophilic compound, a concentrated extract from Prunus mahaleb L. fruit (here named as mcfe) rich in anthocyanins, optimizing its encapsulation and assessing in vitro its release under simulated gastrointestinal conditions. The obtained microbeads were investigated for their morphology and physico-chemical properties under the different pH conditions that characterize the gastrointestinal tract. The novelty in this research was to demonstrate, for the first time the possibility to use Beeswax as wall material, acting as retardant in drug release of phenolic compounds. Chapter 4 summarizes the conclusions made throughout this study and suggests the fulfilment of future works.