Eleni Axioti

Vitamin D deficiency has emerged as a global public health concern, with implications spanning skeletal disorders, cardiovascular diseases, immune dysfunction, and cancer. Despite its biological importance, effective delivery of Vitamin D remains challenging due to its highly lipophilic nature, poor aqueous solubility, and susceptibility to degradation. These physicochemical limitations necessitate the development of advanced delivery systems capable of enhancing stability, bioavailability, and controlled release. In this review, we examine the current understanding of Vitamin D delivery with particular attention being given to colloidal systems such as emulsions, nanoemulsions, liposomes, and micelles, as well as polymeric nanoparticles and hybrid assemblies, which have shown significant promise for encapsulating lipophilic bioactives and improving their bioaccessibility. We discuss how key parameters, including interfacial composition, particle size, and structural organisation, govern the encapsulation efficiency and release behaviour of Vitamin D. Furthermore, we compare the delivery characteristics of the two principal forms, ergocalciferol (Vitamin D2) and cholecalciferol (Vitamin D3), within these systems, highlighting differences in stability and biological performance. Emerging approaches leveraging self-assembly, responsive polymers, and multifunctional carriers are also critically evaluated. Overall, this review provides a formulation perspective on Vitamin D delivery, identifying current challenges and outlining future directions for the rational design of next-generation delivery platforms.

Polymerized cyclic ketene acetals (PCKAs) prepared by radical ring‐opening polymerization (RROP) have shown tremendous potential in the biomedical field. In this work, the field is expanded to the formation of fully degradable nanoparticles (NPs) from the fast‐degrading poly(2‐methylene‐1,3,6‐trioxocane) (PMTC). The formulation of homopolymers is typically challenging due to their lack of amphiphilicity; however, implementing nanoprecipitation as a robust, fast, and cost‐efficient method of self‐assembly has yielded well‐defined polymeric nanocarriers of 100–200 nm in diameter. The characterization of hydrophilicity and dye‐encapsulation mediated via different polyester degrees of branching has enabled insights into utilizing this key characteristic of RROP. The degree of branching affected dye encapsulation in the absence of altering hydrophilicity. The highest levels of encapsulated Coumarine‐6 (Cou6) as a model drug were found with polymers possessing an intermediate degree of branching (8%) at low molecular weight (9 kg/mol). In addition to stable NPs, the disassembly of these NPs in extreme pH regions promised potential for targeted drug delivery. In vitro studies have demonstrated the cytocompatibility of NPs and their degradation products, and their ability to achieve cell uptake of Cou6‐loaded NPs has been confirmed, highlighting the potential of PMTC‐NPs as drug delivery vehicles. The successful protocol to prepare NPs purely of polymerized CKAs demonstrated here thus enables future efforts to expand the library of NPs from RROP.

Many new active pharmaceutical ingredients (APIs) demonstrate high hydrophobicity and low water‐solubility issues. In this regard, polymeric nanoparticles (NPs) have been extensively used as drug delivery carriers for the encapsulation of such APIs. One commonly used polymer is polyethylene glycol (PEG), owing to its biocompatibility, high water solubility, and capacity to prolong the drug residence time. However, concerns have arisen regarding PEG's immunogenicity and limited biodegradability. In addition, inherent limitations, including limited chemical handles can restrict PEG's effectiveness in physiological conditions. For this reason, in the present study, we combine the advantages offered by PEG with the use of an enzymatic synthetic route to produce novel PEGylated polyesters. Furthermore, it has been proven that incorporation of hydrophobic diols into the PEGylated backbone influences NPs formation, stability, and drug encapsulation, despite high chemical similarity. As a preliminary result, samples containing PEG and 1,6‐hexanediol in a 50 : 50 ratio (PEGA‐Hex 50 %) and PEG and 2‐hydroxyethyl disulfide in a 50 : 50 ratio (PEGA‐SS 50 %) have proved to be the most promising candidates in this small library analysed. Both samples exhibited sufficient NPs stability, biocompatibility, and superior encapsulation efficiency compared to the other variants.

The present study investigates the utilization of nanoparticles based on poly-l-lactide (PLLA) and polyglycerol adipate (PGA), alone and blended, for the encapsulation of usnic acid (UA), a potent natural compound with various therapeutic properties including antimicrobial and anticancer activities. The development of these carriers offers an innovative approach to overcome the challenges associated with usnic acid’s limited aqueous solubility, bioavailability, and hepatotoxicity. The nanosystems were characterized according to their physicochemical properties (among others, size, zeta potential, thermal properties), apparent aqueous solubility, and in vitro cytotoxicity. Interestingly, the nanocarrier obtained with the PLLA-PGA 50/50 weight ratio blend showed both the lowest size and the highest UA apparent solubility as well as the ability to decrease UA cytotoxicity towards human hepatocytes (HepG2 cells). This research opens new avenues for the effective utilization of these highly degradable and biocompatible PLLA-PGA blends as nanocarriers for reducing the cytotoxicity of usnic acid.