Search

Multifunctional delivery systems capable of modulating drug release and exerting adjunctive pharmacological activity have attracted particular attention. Chitosan (CS) and pomegranate seed oil (PO) appear to be attractive bioactive components framing the strategy of complex therapy and multifunctional drug carriers. This research is aimed at evaluating the potential of CS in combination with PO in studies on topical emulgels containing hydrocortisone as a model anti-inflammatory agent. Its particular goal was to distinguish alterations in anti-inflammatory action followed with drug dissolution or penetrative behavior between the designed formulations that differ in CS/PO weight ratio. All formulations favored hydrocortisone release with up to a two-fold increase in the drug dissolution rate within first 5 h as compared to conventional topical preparations. The clear effect of CS/PO on the emulgel biological performance was observed, and CS was found to be prerequisite for the modulation of hydrocortisone absorption and accumulation. In turn, a greater amount of PO played the predominant role in the inhibition of hyaluronidase activity and enhanced the anti-inflammatory effect of preparation E-3. Emulgels showed a negligible reduction in mouse fibroblasts' L929 cell viability, confirming their non-irritancy with skin cells. Overall, the designed formulation with a CS/PO ratio of 6:4 appeared to be the most promising topical carrier for the effective treatment of inflammatory skin diseases among the tested subjects.

Centella asiatica extract is a valued plant material with known anti-inflammatory and anti-microbiological properties. Using the Design of Experiment (DoE) approach, it was possible to obtain an optimized water/alcoholic extract from Centella asiatica , which allowed the preparation of the final material with biological activity in the wound healing process. Studies on the novel applications of Centella asiatica in conjunction with the multifunctional chitosan carrier have been motivated by the plant's substantial pharmacological activity and the need to develop new and effective methods for the treatment of chronic wounds. The controlled release of asiaticoside was made possible by the use of chitosan as a carrier. Based on the findings of investigations using the PAMPA skin assay, which is a model imitating the permeability of actives through skin, this compound, characterized by sustained release from the chitosan delivery system, was identified as being well able to permeate biological membranes such as skin. Chitosan and the lyophilized extract of Centella asiatica worked synergistically to block hyaluronidase, exert efficient microbiological activity and take part in the wound healing process, as proven in an in vitro model. A formulation containing 3% extract with 3% medium-molecular-weight chitosan was indicated as a potentially new treatment with high compliance and effectiveness for patients. Optimization of the chitosan-based hydrogel preparation ensured the required rheological properties necessary for the release of the bioactive from the chitosan delivery system and demonstrated a satisfactory antimicrobial activity.

Orange peel, which is a rich source of polyphenolic compounds, including hesperidin, is produced as waste in production. Therefore, optimization of the extraction of hesperidin was performed to obtain its highest content. The influence of process parameters such as the kind of extraction mixture, its temperature and the number of repetitions of the cycles on hesperidin content, the total content of phenolic compounds and antioxidant (DPPH scavenging assay) as well as anti-inflammation activities (inhibition of hyaluronidase activity) was checked. Methanol and temperature were key parameters determining the efficiency of extraction in terms of the possibility of extracting compounds with the highest biological activity. The optimal parameters of the orange peel extraction process were 70% of methanol in the extraction mixture, a temperature of 70 °C and 4 cycles per 20 min. The second part of the work focuses on developing electrospinning technology to synthesize nanofibers of polyvinylpyrrolidone (PVP) and hydroxypropyl-β-cyclodextrin (HPβCD) loaded with hesperidin-rich orange peel extract. This is a response to the circumvention of restrictions in the use of hesperidin due to its poor bioavailability resulting from low solubility and permeability. Dissolution studies showed improved hesperidin solubility (over eight-fold), while the PAMPA-GIT assay confirmed significantly better transmucosal penetration (over nine-fold). A DPPH scavenging assay of antioxidant activity as well as inhibition of hyaluronidase to express anti-inflammation activity was established for hesperidin in prepared electrospun nanofibers, especially those based on HPβCD and PVP. Thus, hesperidin-rich orange peel nanofibers may have potential buccal applications to induce improved systemic effects with pro-health biological activity.

Hot Melt Extrusion (HME) technology was developed to obtain blends containing lyophilized Scutellariae baicalensis root extract and chitosan in order to improve the rheological properties of the obtained blends, including tableting and compressibility properties. (Hydroxypropyl)methyl cellulose (HPMC) in 3 different ratios was used as amorphous matrix formers. The systems were characterized using X-ray powder diffraction (PXRD), Fourier Transform Infrared Spectroscopy with Attenuated Total Reflectance (FTIR-ATR), and in vitro release, permeability, and microbiological activity studies. Then, the extrudates were used to prepare tablets in order to give them the appropriate pharmaceutical form. HPMC-based systems released baicalin more slowly, resulting in delayed peaks in the acceptor fluid. This behavior can be explained by the fact that HPMC swells significantly, and the dissolved substance must have diffused through the polymer network before being released. The best tabletability properties are provided by the formulation containing the extrudate with lyophilized extract HPMC 50:50 w / w . These tablets offer a valuable baicalin release profile while maintaining good mucoadhesive properties that condition the tablet's retention in the application site and the effectiveness of therapy.

Progressive increase in bacterial resistance has caused an urgent need to introduce new antibiotics, one of them being oxazolidinones with their representative tedizolid. Despite the broad spectrum of activity of the parent tedizolid, it is characterized by low water solubility, which limits its use. The combination of the active molecule with a multifunctional excipient, which is cyclodextrins, allows preservation of its pharmacological activity and modification of its physicochemical properties. Therefore, the aim of the study was to change the dissolution rate and permeability through the model membrane of tedizolid by formation of solid dispersions with a cyclodextrin. The research included identification of tedizolid-hydroxypropyl-β-cyclodextrin (tedizolid/HP-β-CD) inclusion complex by thermal method (Differential Scanning Colorimetry), spectroscopic methods (powder X-ray diffraction, Fourier-Transform Infrared spectroscopy), and molecular docking. The second part of the research concerned the physicochemical properties (dissolution and permeability) and the biological properties of the system in terms of its microbiological activity. An increase in the dissolution rate was observed in the presence of cyclodextrin, while maintaining a high permeation coefficient and high microbiological activity. The proposed approach is an opportunity to develop drug delivery systems used in the treatment of resistant bacterial infections, in which, in addition to modifying the physicochemical properties caused by cyclodextrin, we observe a favorable change in the pharmacological potential of the bioactives.