Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor. Residual cells at the tumor margin are responsible for up to 85% of GBM recurrences after standard treatment. Despite this evidence, the identification of compounds active on this cell population is still an underexplored field. Herein, starting from the knowledge that kinases are implicated in GBM, we evaluated three in-house pyrazolo[3,4-d]pyrimidines active as Src, Fyn, and SGK1 kinase inhibitors against patient derived cell lines from either the invasive region or contrast-enhanced core of GBM. We identified our Src inhibitor, SI306, as a promising lead compound for eradicating invasive GBM cells. Furthermore, aiming at the development of a feasible oral treatment for GBM, we performed a formulation study using 2D inkjet printing to generate soluble polymer–drug dispersions. Overall, this study led to the identification of a set of polymer-formulated pyrazolo[3,4-d]pyrimidine kinase inhibitors as promising candidates for GBM preclinical efficacy studies.

Combinations of the topoisomerase II inhibitor doxorubicin and the poly (ADP-ribose) polymerase inhibitor olaparib offer potential drug–drug synergy for treatment of triple negative breast cancers (TNBC) both in free drug form and when delivered by oxidation-responsive nanoparticles.

Biocompatible and bio-based materials are an appealing resource for the pharmaceutical industry. Poly(glycerol-adipate) (PGA) is a biocompatible and biodegradable polymer that can be used to produce self-assembled nanoparticles (NPs) able to encapsulate active ingredients, with encouraging perspectives for drug delivery purposes. Starch is a versatile, inexpensive, and abundant polysaccharide that can be effectively applied as a bio-scaffold for other molecules in order to enrich it with new appealing properties. In this work, the combination of PGA NPs and starch films proved to be a suitable biopolymeric matrix carrier for the controlled release preparation of hydrophobic drugs. Dynamic Light Scattering (DLS) was used to determine the size of drug-loaded PGA NPs, while the improvement of the apparent drug water solubility was assessed by UV-vis spectroscopy. In vitro biological assays were performed against cancer cell lines and bacteria strains to confirm that drug-loaded PGA NPs maintained the effective activity of the therapeutic agents. Dye-conjugated PGA was then exploited to track the NP release profile during the starch/PGA nanocomposite film digestion, which was assessed using digestion models mimicking physiological conditions. The collected data provide a clear indication of the suitability of our biodegradable carrier system for oral drug delivery.

Despite the success of polyethylene glycol-based (PEGylated) polyesters in the drug delivery and biomedical fields, concerns have arisen regarding PEG's immunogenicity and limited biodegradability. In addition, inherent limitations, including limited chemical handles as well as highly hydrophobic nature, can restrict their effectiveness in physiological conditions of the polyester counterpart. To address these matters, an increasing amount of research has been focused towards identifying alternatives to PEG. One promising strategy involves the use of bio-derived polyols, such as glycerol. In particular, glycerol is a hydrophilic, non-toxic, untapped waste resource and as other polyols, can be incorporated into polyesters via enzymatic catalysis routes. In the present study, a systematic screening is conducted focusing on the incorporation of 1,6-hexanediol (Hex) (hydrophobic diol) into both poly(glycerol adipate) (PGA) and poly(diglycerol adipate) (PDGA) at different (di)glycerol:hex ratios (30:70; 50:50 and 70:30 mol/mol) and its effect on purification upon NPs formation. By varying the amphiphilicity of the backbone, we demonstrated that minor adjustments influence the NPs formation, NPs stability, drug encapsulation, and degradation of these polymers, despite the high chemical similarity. Moreover, the best performing materials have shown good biocompatibility in both in vitro and in vivo (whole organism) tests. As preliminary result, the sample containing diglycerol and Hex in a 70:30 ratio, named as PDGA-Hex 30%, has shown to be the most promising candidate in this small library analysed. It demonstrated comparable stability to the glycerol-based samples in various media but exhibited superior encapsulation efficiency of a model hydrophobic dye. This in-depth investigation provides new insights into the design and modification of biodegradable (di)glycerol-based polyesters, potentially paving the way for more effective and sustainable PEG-free drug delivery nano-systems in the pharmaceutical and biomedical fields.

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.

The therapeutic efficacy of anticancer nanocarriers ishighly dependent on their size, shape, targeting ability, andstimuli-responsiveness. Herein, we studied the in vivo therapeutic efficacy ofDoxorubicin (Dox) loaded redox responsive micellar-like nanoparticles (MNPs)based on linear 2-hydroxypropyl methacrylamide (HPMA) via histopathologicalevaluations. The therapeutic efficacy of DOX-loaded micellar-like Nanoparticlessignificantly improved while the side effects reduced as confirmed byhistopathological examinations. H&E and tunnel staining of tumor tissuesindicated the higher population of apoptotic tumor cells in both treatmentgroups containing DOX. These redox responsive crosslinked HPMA-basedmicellar-like nanoparticles with acceptable therapeutic efficacy and apoptosisinduction in cancerous cells proved to be promising nanomedicine for breast cancer chemotherapy.