Katarina Sokač

Achieving precise control over anticancer drug release remains one of the key challenges in modern pharmaceutical development, as it directly determines therapeutic efficacy, systemic toxicity, and patient outcomes. This review critically evaluates recent advances in three major formulation strategies: polymeric solid dispersions, cyclodextrin-based inclusion complexes, and metal–organic frameworks (MOFs), with a particular focus on their capacity to tailor anticancer drug release. Over the past decade, polymeric solid dispersions and cyclodextrin-based carriers have played a central role in improving the dissolution and bioavailability of poorly water-soluble anticancer agents, while also enabling modified release profiles through rational formulation design. Increasing structural complexity, including ternary systems and supramolecular assemblies, reflects a shift toward more controllable delivery platforms. In recent years, MOFs have emerged as highly adaptable porous materials capable of supporting controlled and stimuli-responsive release. The integration of imaging agents, magnetic components, and photothermal functionalities has further enabled the design of multifunctional and theranostic platforms. Taken together, these technologies reflect a shift from conventional solubility enhancement toward structurally engineered systems designed to achieve predictable and controlled drug release. Continued advances in material design and formulation strategies are expected to further refine release kinetics and support the development of next-generation anticancer therapies aligned with the growing demand for precision medicine.

Dasatinib (DAS) je djelatna tvar koja se upotrebljava u liječenju kronične mijeloične i akutne limfoblastične leukemije. Tu djelatnu tvar karakteriziraju dobra intestinalna permeabilnost te loša topljivost u vodenom mediju, što može dovesti do smanjene oralne apsorpcije djelatne tvari i niske bioraspoloživosti lijeka. U svrhu modifikacije oslobađanja DAS-a, mehanokemijski su pripravljene čvrste disperzije DAS-a i poli(vinil-pirolidona) (PVP) (uz maseni udio DAS-a od 25 %) u planetarnom kugličnom mlinu pri četiri različita seta procesnih uvjeta. Čvrste disperzije pripravljene su bez otapala, poštujući načela zelene kemije. Pripravljene disperzije karakterizirane su diferencijalnom pretražnom kalorimetrijom, rendgenskom difrakcijskom analizom praha i infracrvenom spektroskopijom s Fourierovim transformacijama da bi se detektirala toplinska svojstva i fazni sastav čvrstih disperzija te potencijalne interakcije između DAS-a i PVP-a. Izrađene su četiri vrste tableta koje sadrže: ishodni DAS, mehanokemijski tretiran DAS, fizikalnu mješavinu DAS-a i PVP-a te čvrstu disperziju DAS-a i PVP-a pripravljenu pri naknadno utvrđenim optimalnim procesnim uvjetima. U pripravi svih vrsta tableta upotrijebljen je granulat pomoćnih tvari: manitola, natrijeve kroskarmeloze i poli(etilen-glikola). Tablete su testirane na ujednačenost mase i sadržaja djelatne tvari, čvrstoću i raspadljivost. Profili oslobađanja DAS-a određeni su testovima otapanja in vitro. Mehanokemijskom pripravom amorfnih čvrstih disperzija modificiran je profil oslobađanja DAS-a.

Dasatinib (DAS) is a second‐generation tyrosine kinase inhibitor used in the treatment of Philadelphia chromosome‐positive chronic myeloid leukemia and acute lymphoblastic leukemia. Nevertheless, this drug is hindered by poor gastrointestinal absorption and limited bioavailability, primarily attributable to its low aqueous solubility. To improve its properties, solid dispersions of DAS within a matrix of the hydrophilic polymer polyvinylpyrrolidone (PVP) are prepared by cogrinding in a vibrational ball mill at various drug‐to‐polymer ratios. The prepared solid dispersions are thoroughly characterized by several methods to verify the drug's amorphization and enhanced wettability as a result of successful mechanochemical activation. Fluidized bed melt granulation and traditional tableting are used to prepare tablets of 8 mm diameter with strictly defined aimed properties. Characterization of tablets includes testing their hardness, disintegration, and in vitro dissolution. The in vitro release profiles reveal a significant improvement in the release rate of DAS from tablets containing solid dispersion with the highest polymer ratio when compared with those containing untreated DAS or solid dispersions with a low polymer ratio. The results confirm the significant effect of the PVP ratio in solid dispersions on the surface characteristics and dissolution rate of DAS.

Dasatinib (DAS), a potent anticancer drug, has been subjected to formulation enhancements due to challenges such as significant first-pass metabolism, poor absorption, and limited oral bioavailability. To improve its release profile, DAS was embedded in a matrix of the hydrophilic polymer polyvinylpyrrolidone (PVP). Drug amorphization was induced in a planetary ball mill by solvent-free co-grinding, facilitating mechanochemical activation. This process resulted in the formation of amorphous solid dispersions (ASDs). The ASD capsules exhibited a notable enhancement in the release rate of DAS compared to capsules containing the initial drug. Given that anticancer drugs often undergo limited metabolism in the body with unchanged excretion, the ecotoxicological effect of the native form of DAS was investigated as well, considering its potential accumulation in the environment. The highest ecotoxicological effect was observed on the bacteria Vibrio fischeri, while other test organisms (bacteria Pseudomonas putida, microalgae Chlorella sp., and duckweed Lemna minor) exhibited negligible effects. The enhanced drug release not only contributes to improved oral absorption but also has the potential to reduce the proportion of DAS that enters the environment through human excretion. This comprehensive approach highlights the significance of integrating advances in drug development while considering its environmental implications.

Dental caries and periodontitis are the most common diseases of the oral cavity and can develop into life-threatening health conditions. Both diseases are multifactorial chronic diseases in which pathogenic microorganisms play an important role in disease progression. Several studies suggest that probiotics may play an important role in preventing of such diseases. In this study, lactic acid bacteria isolated from mare and donkey milk were evaluated for their potential as dental probiotics. The ability to survive and form biofilms in the oral cavity, as well as the antimicrobial and coaggregative abilities against cariogenic streptococci and periodontitis-related P. gingivalis and A. actinomycetemcomitans were investigated. Two L. plantarum strains showed high probiotic potential. Together with high aggregation and antimicrobial activity, investigated strains displayed the ability to prevent biofilm formation of the tested pathogens. Our results suggest that there are several ways to exert antimicrobial activity and that the tested probiotic characteristics are strain-dependent. This study characterizes for the first time naturally occurring bacteria from mare and donkey milk for use in the preservation of dental health. Equid milk appears to be a potent new source of probiotic bacteria that can be used to reduce or prevent dental disease.