Special Issue on Advanced Applications of Bioencapsulation Technologies

Bioencapsulation involves the envelopment of bioactive compounds or cells to host and protect them from chemical/physical degradation and biological attack from hazardous species or undesired immune responses [1,2,3]. The term bioencapsulation commonly encompasses all coating approaches aimed at preserving the functionality of embedded species. It can also be extended to the development of biomimetic matrices and biomaterials that encapsulate cells to provide environmental signals, to induce tunable structural and genetic modifications, to trigger specific responses, and to study cell–matrix interactions [4,5,6].

Accordingly, the fields of application are very broad, as are the bioencapsulation techniques developed. The food industry, pharmaceutical companies, and developers of medical devices are investing vast resources in the search for optimal encapsulation solutions.

Chemical oxidation and photo-oxidation are the most common issues in the food industry [7], whereas in the pharmaceutical field, it is of paramount importance to increase the biostability, bioavailability, and biodistribution of active ingredients [8,9]. Additionally, immune-isolation using encapsulation techniques is a strategic approach to prolonging the lifetimes of xenograft transplanted tissues and organs [10].

In this Special Issue, original research and review contributions spanning several fields of the above-mentioned applications have been collected.

The group of C.W. Cho showed that spray-drying is a convenient approach to obtaining solid formulations of omega-3 fatty acids, which are nutrients important for preventing and managing heart disease [11]. Dry forms of this active ingredient are strongly preferred, as they display enhanced stability, a lower tendency for contamination, and ease in storage and transport. In detail, 28 formulations were prepared using olive oil as a substitute for omega-3, and several pharmaceutical excipients, such as methyl cellulose, hydroxy methyl cellulose, polyvinylpyrrolidone, gelatin A, gelatin B, α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin with poloxamer 188. γ-cyclodextrin allowed the best spray-dried formulation to be obtained.

A common approach to preserving the bioactivity of active ingredients that need to be orally administered is encapsulation with molecules resistant to the acidic environment of the stomach. In the work by Souza et al., the water-in-water emulsion method was used to prepare xylan–PEG microparticles containing mesalamine [12]. Xylan is the second most abundant polysaccharide and is characterized by good biocompatibility and selective degradation in the gastrointestinal tract through enzymatic hydrolysis by the colon microbiota. Mesalamine has an anti-inflammatory effect on colonic epithelial cells and is used to treat ulcerative colitis. Several formulations composed of different xylan/PEG ratios were prepared; only a few of them reached up to 50% of drug loading and retained almost 40% of the drug content after a dissolution assay.

Due to their high biocompatibility and chemical stability, ease of functional derivatization, and immune-shielding behavior, PEG molecules are often used as pharmaceutical excipients and polymer coatings for surfaces, colloids, and cell clusters. An example is an antibody-bearing PEG shell grown over pancreatic islets, proposed by Cavallo et al. [13]. The goal of their study was to develop an immune-encapsulation strategy to reduce the risk of the rejection of transplants in patients due to the immune response of the host organism. As a proof of concept, the site-oriented functionalization of an anti-GFP (green fluorescent protein) antibody to acryl PEG was successfully demonstrated prior to encapsulating the pancreatic islets within the antibody–PEG shell. Finally, the selective binding of GFP to the antibody produced a uniform fluorescent corona around the islets.

Cell encapsulation in hydrogels or porous matrices has been widely investigated in tissue-engineering applications [14]. Polysaccharide-based hydrogels, such as alginate, chitosan, and dextran, or proteins such as collagen, silk, and elastin are the components most commonly explored to date [15,16,17]. Among them, chitosan plays a key role. In this Special Issue, two contributions exploited this polymer for different purposes. Stanzione et al. developed an injectable form of chitosan for in situ hydrogel formation for tissue engineering. The addition of salts, such as beta-glycerol phosphate and sodium hydrogen carbonate, allowed them to obtain stable and biocompatible formulations, which gelled under physiological conditions at 37 °C. This study aimed to realize hydrogels with high swelling ratios and mechanical stiffnesses suitable for cell encapsulation [18]. In another study, by Confederat et al., chitosan was used to obtain microparticles, through the ionic gelation method, for the encapsulation of glibenclamide (Gly) and lipoic acid (LA). These two compounds, an antidiabetic that stimulates insulin production and an antioxidant, respectively, are used in the management of diabetes mellitus. The entrapment efficiency was very high for Gly, with a high percentage release efficiency for both drugs. The swelling data showed a fine behavior in simulated gastric fluid, suggesting potential for the preparations to be used with oral administration [19].

From the cell level to the nano- and microparticle levels, the techniques of encapsulation have rapidly evolved in the last few years, from simple polymer shells to more sophisticated stimulus-responsive coatings or multiple layers with tunable chemical/biological affinity. Inorganic materials such as silica have also been considered. Indeed, silica facilitates several synthetic strategies and is very well suited to the controlled encapsulation of inorganic nanoparticles, for the protection of the core or to increase the system biocompatibility. Fanizza et al. showed how the introduction of giant quantum dots (GQDs), namely, organic capped PbS@CdS@CdS, in a silica shell allowed the exploitation of their optical properties for temperature monitoring. Through a microemulsion process, the GQDs were individually encapsulated in a silica shell of 10–15 nm. Temperature variations influence the ratio between the two integrated PbS and CdS emission bands of GQDs. This peculiarity was also maintained after silica shell growth, with a ratiometric response (I_PbS/I_CdS) that monotonically decreased with the temperature, with a sensitivity of 0.01 K⁻¹ [20]. Nemec and Kralj et al. investigated the contribution of a silica shell in the hyperthermia profiles of maghemite nanoparticles. These magnetic nanoparticles could be used as heating agent through magnetic hyperthermia or laser-assisted photothermia, exploiting different mechanisms. The study demonstrated that the encapsulation of the nanoparticles in the shell enhanced the heating performance in photothermia, due to the increased thermal conductivity of the fluid. For magnetic hyperthermia, the suppression of the Brownian relaxation (which reduced the hyperthermia efficiency in other studies) was counterbalanced by the faster heat dissipation of the silica shell, resulting in comparable heating outcomes between individual nanoparticles and silica-encapsulated ones [21].

Finally, it is worth mentioning the review by Zafar and Ragusa that analyzed the implications of using chiral molecules as surface coatings for nanoparticles and the recent applications of chiral nanoparticles in four major research fields: enantioselective recognition, asymmetric catalysis, biomedicine, and biosensing [22]. Chiral molecules, such as peptides and oligosaccharides, allow the establishment of specific interactions with the target, which could be a membrane receptor or intracellular target. Chiral molecules are fundamental in many chemical and biological synthetic processes. It is known that active pharmaceutical ingredients often contain at least one chiral center; however, only one enantiomer exerts beneficial pharmacological effects, while the other is inactive or may even be toxic [23]. Similarly, enantioselective coatings on the nanoparticle surface may be fundamental for specific recognition and binding.

The brief analysis of these contributions evidences the broad fields of application for bioencapsulation technologies and the great interest of the scientific community, as confirmed by the number of review articles published on this topic in last two years by Applied Sciences [1,2,24,25,26,27,28]. All the published articles provide different perspectives on the preparation and optimization of biomaterials for achieving the efficient encapsulation of organic or inorganic compounds, with good outcomes for applications in biomedicine.