## 3 Encapsulation Techniques for Improving Phenolic Compounds Functionality
### Encapsulated Phenolic Compounds as Antidiabetic Agents  
Several phenolic compounds have been encapsulated to improve their suitability as a tool in managing diabetes and CVDs. The following paragraphs provide a summary of the strategies followed and the main outcomes of each approach. Table 2 summarizes the materials and encapsulation strategies that have been proven effective for the encapsulation of some of the most studied. Curcumin, long known for its medicinal uses, is a polyphenol derived from turmeric (_Curcuma longa_) and belongs to the subgroup of curcuminoids [107]. This polyphenol shows anti-inflammatory, antioxidant, anti-cancer, and hypolipidemic effects [107, 108]. Due to its low hydrophilicity, nano-encapsulation is an excellent solution to enhance its solubility [109]. There are reports of various encapsulation approaches to the use of curcumin to treat diabetes and related diseases [108, 109]. A good example is an encapsulation of curcumin in poly(gamma-benzyl-1-glutamate)-poly(ethyleneglycol)-poly(gamma-benzylglutamate) nanoparticles prepared by ring-opening polymerisation, which enhanced its bioactivity and water solubility [97]. This nanosystem demonstrated a potent effect in attenuating diabetic cardiomyopathy, which might lead to heart failure and myocardial ischaemia [97], by allowing curcumin to cross-regulate receptors responsible for calcium-sensing (CaSR) and the endogenous cystathionine \(\gamma\)-lyase/hydrogen sulphide system (CSE/H2S) [97]. Furthermore, a formulation of curcumin encapsulated in polybutylcyanoacrylate-based nanoparticles, prepared by anionic emulsion polymerisation, has been used to treat diabetic peripheral neuropathy, which usually occurs as a consequence of type II diabetes and leads to neuropathy [98]. Oral ingestion of this curcumin nanoformulation significantly lowered plasma serum levels of total cholesterol, C reactive protein, interleukin-6, and triglycerides, and increased HDL cholesterol [98]. In addition, the curcumin-loaded nanoformulation effectively alleviated diabetic neuropathy-induced pain in rats [98]. In another _in vivo_ study, curcumin nanoparticles (CNPs), prepared by a re-precipitation method, were embedded into a thermosensitive hydrogel containing matrix metalloproteinase 9 (MMP9) to provide a safe and efficient system to promote skin wound healing in diabetic patients [99]. It has been demonstrated that such a structure can induce controlled drug release at the wound bed and promote efficacy in healing skin wounds in diabetic rat models by decreasing ROS and promoting cell migration to restore normal skin structures and function [99]. Berberine, an essential benzylisoquinoline alkaloid from _Coptis chinensis_, has been used to treat diabetes, cancer, hyperlipidaemia, and cognitive heart failure [109, 110]. Nanoformulations of berberine have been demonstrated to ameliorate its bioavailability. A nanoformulation of berberine encapsulated in polyethylene glycol-co-lactic acid-glycolic acid (PEG-PLGA) nanoparticles, designed to be administered orally, was successfully tested _in vitro_ to reduce intracellular levels ofoprotein convertase subtilisin/kexin type 9 (PCSK9) in hepatocytes, which contributes to lower plasma LDL-cholesterol levels [101]. Naringenin is a type of flavone found primarily in citrus fruits and vegetables with potential antioxidant, blood-sugar-lowering, anti-inflammatory, and anti-cancer properties [111]. Naringenin encapsulated in chitosan-coated alginate core-shell nanoparticles, ranging in size from 158 to 300 nm, improved the solubility of the flavonoid. The nanoformulation had excellent entrapment efficiency (90%) and allowed controlled release. In an _in vivo_ assay, these naringenin nanoparticles showed a high anti-diabetic effect with low toxicity when administered orally to diabetic rat models [100].