Improving Solubility and Permeability of Hesperidin through Electrospun Orange-Peel-Extract-Loaded Nanofibers.

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-ß-cyclodextrin (HPßCD) 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 HPßCD and PVP. Thus, hesperidin-rich orange peel nanofibers may have potential buccal applications to induce improved systemic effects with pro-health biological activity.

Screening of the Anti-Neurodegenerative Activity of Caffeic Acid after Introduction into Inorganic Metal Delivery Systems to Increase Its Solubility as the Result of a Mechanosynthetic Approach.

The proven anti-neurodegenerative properties of caffeic acid in vivo are limited due to its poor solubility, which limits bioavailability. Therefore, caffeic acid delivery systems have been developed to improve caffeic acid solubility. Solid dispersions of caffeic acid and magnesium aluminometasilicate (Neusilin US2-Neu) were prepared using the ball milling and freeze-drying techniques. The solid dispersions of caffeic acid:Neu obtained by ball milling in a 1:1 mass ratio turned out to be the most effective. The identity of the studied system in comparison to the physical mixture was confirmed using the X-Ray Powder Diffractionand Fourier-transform infrared spectroscopy techniques. For caffeic acid with improved solubility, screening tests were carried out to assess its anti-neurodegenerative effect. The obtained results on the inhibition of acetylcholinesterase, butyrylcholinesterase, tyrosinase, and antioxidant potential provide evidence for improvement of caffeic acid's anti-neurodegenerative activity. As a result of in silico studies, we estimated which caffeic acid domains were involved in interactions with enzymes showing expression relevant to the neuroprotective activity. Importantly, the confirmed improvement in permeability of the soluble version of caffeic acid through membranes simulating the walls of the gastrointestinal tract and blood-brain barrier further strengthen the credibility of the results of in vivo anti-neurodegenerative screening tests.

Hot Melt Extrusion as an Effective Process in the Development of Mucoadhesive Tablets Containing Scutellariae baicalensis radix Extract and Chitosan Dedicated to the Treatment of Oral Infections.

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.

Amorphous System of Hesperetin and Piperine-Improvement of Apparent Solubility, Permeability, and Biological Activities.

The low bioaccessibility of hesperetin and piperine hampers their application as therapeutic agents. Piperine has the ability to improve the bioavailability of many compounds when co-administered. The aim of this paper was to prepare and characterize the amorphous dispersions of hesperetin and piperine, which could help to improve solubility and boost the bioavailability of both plant-origin active compounds. The amorphous systems were successfully obtained by means of ball milling, as confirmed by XRPD and DSC studies. What's more, the FT-IR-ATR study was used to investigate the presence of intermolecular interactions between the systems' components. Amorphization enhanced the dissolution rate as a supersaturation state was reached, as well as improving the apparent solubility of both compounds by 245-fold and 183-fold, respectively, for hesperetin and piperine. In the in vitro permeability studies simulating gastrointestinal tract and blood-brain barrier permeabilities, these increased by 775-fold and 257-fold for hesperetin, whereas they were 68-fold and 66-fold for piperine in the GIT and BBB PAMPA models, respectively. Enhanced solubility had an advantageous impact on antioxidant as well as anti-butyrylcholinesterase activities-the best system inhibited 90.62 ± 0.58% of DPPH radicals and 87.57 ± 1.02% butyrylcholinesterase activity. To sum up, amorphization considerably improved the dissolution rate, apparent solubility, permeability, and biological activities of hesperetin and piperine.

Zein as an Effective Carrier for Hesperidin Delivery Systems with Improved Prebiotic Potential.

Hesperidin is a polyphenol derived from citrus fruits that has a broad potential for biological activity and the ability to positively modify the intestinal microbiome. However, its activity is limited by its low solubility and, thus, its bioavailability-this research aimed to develop a zein-based hesperidin system with increased solubility and a sustained release profile. The study used triple systems enriched with solubilizers to maximize solubility. The best system was the triple system hesperidin-zein-Hpß-CD, for which the solubility improved by more than six times. A significant improvement in the antioxidant activity and the ability to inhibit α-glucosidase was also demonstrated, due to an improved solubility. A release profile analysis was performed in the subsequent part of the experiments, confirming the sustained release profile of hesperidin, while improving the solubility. Moreover, the ability of selected probiotic bacteria to metabolize hesperidin and the effect of this flavonoid compound on their growth were investigated.

Preparation of Thin Films Containing Modified Hydroxyapatite Particles and Phospholipids (DPPC) for Improved Properties of Biomaterials.

The main aims of thin biofilm synthesis are to either achieve a new form to promote the transport of drugs in oral delivery systems or as a coating to improve the biocompatibility of the implant's surface. In this study, the Langmuir monolayer technique was employed to obtain films containing Mg-doped hydroxyapatite with 0.5%, 1.0%, and 1.5% Mg(II). The obtained modified HA particles were analysed via the FT-IR, XRD, DLS, and SEM methods. It was shown that the modified hydroxyapatite particles were able to form thin films at the air/water interface. BAM microscopy was employed to characterized the morphology of these films. In the next step, the mixed films were prepared using phospholipid (DPPC) molecules and modified hydroxyapatite particles (HA-Mg(II)). We expected that the presence of phospholipids (DPPC) in thin films improved the biocompatibility of the preparing films, while adding HA-Mg(II) particles will promote antibacterial properties and enhance osteogenesis processes. The films were prepared in two ways: (1) by mixing DPPC and HA-Mg (II) and spreading this solution onto the subphase, or (2) by forming DPPC films, dropping the HA-Mg (II) dispersion onto the phospholipid monolayer. Based on the obtained π-A isotherms, the surface parameters of the achieved thin films were estimated. It was observed that the HA-Mg(II) films can be stabilized with phospholipid molecules, and a more stable structure was obtained from films synthesied via method (2).

The Systems of Naringenin with Solubilizers Expand Its Capability to Prevent Neurodegenerative Diseases.

BACKGROUND: Naringenin (NAR) is a flavonoid with excellent antioxidant and neuroprotective potential that is limited by its low solubility. Thus, solid dispersions with ß-cyclodextrin (ß-CD), hydroxypropyl-ß-cyclodextrin (HP-ß-CD), hydroxypropylmethylcellulose (HPMC), and microenvironmental pH modifiers were prepared. METHODS: The systems formation analysis was performed by X-Ray Powder Diffraction (XRPD) and Fourier-transform infrared spectroscopy (FT-IR). Water solubility and dissolution rates were studied with a pH of 1.2 and 6.8. In vitro permeability through the gastrointestinal tract (GIT) and the blood-brain barrier (BBB) was assessed with the parallel artificial membrane permeability assay (PAMPA) assay. The antioxidant activity was studied with the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and cupric ion reducing antioxidant capacity (CUPRAC) assays, while in vitro enzymes studies involved the inhibition of acetylcholinesterase, butyrylcholinesterase, and tyrosinase. For the most promising system, in silico studies were conducted. RESULTS: NAR solubility was increased 458-fold by the solid dispersion NAR:HP-ß-CD:NaHCO3 in a mass ratio of 1:3:1. The dissolution rate was elevated from 8.216% to 88.712% in a pH of 1.2 and from 11.644% to 88.843% in a pH of 6.8 (within 3 h). NAR GIT permeability, described as the apparent permeability coefficient, was increased from 2.789 × 10-6 cm s-1 to 2.909 × 10-5 cm s-1 in an acidic pH and from 1.197 × 10-6 cm s-1 to 2.145 × 10-5 cm s-1 in a basic pH. NAR BBB permeability was established as 4.275 × 10-6 cm s-1. The antioxidant activity and enzyme inhibition were also increased. Computational studies confirmed NAR:HP-ß-CD inclusion complex formation. CONCLUSIONS: A significant improvement in NAR solubility was associated with an increase in its biological activity.

Amorphous Form of Carvedilol Phosphate-The Case of Divergent Properties.

The amorphous form of carvedilol phosphate (CVD) was obtained as a result of grinding. The identity of the obtained amorphous form was confirmed by powder X-ray diffraction (PXRD), different scanning calorimetry (DSC), and FT-IR spectroscopy. The process was optimized in order to obtain the appropriate efficiency and time. The crystalline form of CVD was used as the reference standard. Solid dispersions of crystalline and amorphous CVD forms with hydrophilic polymers (hydroxypropyl-ß-cyclodextrin, Pluronic® F-127, and Soluplus®) were obtained. Their solubility at pH 1.2 and 6.8 was carried out, as well as their permeation through a model system of biological membranes suitable for the gastrointestinal tract (PAMPA-GIT) was established. The influence of selected polymers on CVD properties was defined for the amorphous form regarding the crystalline form of CVD. As a result of grinding (four milling cycles lasting 15 min with 5 min breaks), amorphous CVD was obtained. Its presence was confirmed by the "halo effect" on the diffraction patterns, the disappearance of the peak at 160.5 °C in the thermograms, and the changes in position/disappearance of many characteristic bands on the FT-IR spectra. As a result of changes in the CVD structure, its lower solubility at pH 1.2 and pH 6.8 was noted. While the amorphous dispersions of CVD, especially with Pluronic® F-127, achieved better solubility than combinations of crystalline forms with excipients. Using the PAMPA-GIT model, amorphous CVD was assessed as high permeable (Papp > 1 × 10-6 cm/s), similarly with its amorphous dispersions with excipients (hydroxypropyl-ß-cyclodextrin, Pluronic® F-127, and Soluplus®), although in their cases, the values of apparent constants permeability were decreased.

Hydroxypropyl-ß-cyclodextrin as an effective carrier of curcumin - piperine nutraceutical system with improved enzyme inhibition properties.

The nutraceutical system of curcumin-piperine in 2-hydroxypropyl-ß-cyclodextrin was prepared by using the kneading technique. Interactions between the components of the system were defined by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR). Application of hydroxypropyl-ß-cyclodextrin as a carrier-solubiliser improved solubility of the curcumin-piperine system, its permeability through biological membranes (gastrointestinal tract, blood-brain barrier) as well as the antioxidant, antimicrobial and enzyme inhibitory activities against acetylcholinesterase and butyrylcholinesterase.

Machine Learning Approach for Determining the Formation of ß-Lactam Antibiotic Complexes with Cyclodextrins Using Multispectral Analysis.

The problem of determining the formation of complexes of ß-lactam antibiotics with cyclodextrins (CDs) and the interactions involved in this process were addressed by machine learning on multispectral images. Complexes of ß-lactam antibiotics, including cefuroxime axetil, cefetamet pivoxil, and pivampicillin, as well as CDs, including αCD, ßCD, γCD, hydroxypropyl-αCD, methyl-ßCD, hydroxypropyl-ßCD, and hydroxypropyl-γCD, were prepared in all combinations. Thermograms confirming the formation of cyclodextrin complexes were obtained using differential scanning calorimetry. Transmission Fourier-transform infrared (tFTIR) and complementary attenuated total reflectance FTIR (ATR) coupled with machine learning were techniques chosen as a nondestructive alternative. The machine learning algorithm was used to determine the formation of complexes in samples using solely their tFTIR and ATR spectra at the prediction stage. Parameterized method 7 (PM7) was used to support the analysis by molecular modeling of the complexes. The model developed through machine learning properly distinguished samples with formed complexes form noncomplexed samples with a cross-validation accuracy of 90.4%. Analysis of the contribution of spectral bands to the model indicated interactions of ester groups of ß-lactam antibiotics with CDs, as well as some interactions of cephem ring in cefetamet pivoxil and penam moiety in pivampicillin. Molecular modeling with PM7 helped to explain experimental results and allowed to propose possible binding modes.

The Radiation Sterilization of Ertapenem Sodium in the Solid State.

For the first time, the influence of ionising radiation on the physicochemical properties of ertapenem in solid state was studied. During our studies, we evaluated the possibility of applying radiosterilization to obtain sterile ertapenem. Spectroscopic (Fourier Transform Infrared (FT-IR)), thermal (differential scanning calorimetry (DSC), chromatography (High-Performance Liquid Chromatography (HPLC) and HPLC-MS), and X-ray powder diffraction (XRPD) studies shown that irradiation of ertapenem with the 25 kGy, the dose required to achieve sterility, does not change the physicochemical properties of the studied compound. The antimicrobial activity of ertapenem irradiated with the dose of 25 kGy was only reduced for one species. Based on the received results, we can conclude that radiostelization is a promising alternative method of obtaining sterile ertapenem. In our studies, ertapenem was also exposed to e-beam radiation with a dose of 400 kGy. It was determined that two novel degradation products that are structurally differently to degradants formed during hydrolysis and thermolysis.

Effects of inclusion of cetirizine hydrochloride in ß-cyclodextrin.

Following the preparation of inclusion complex of cetirizine (CTZ) and ß-cyclodextrin (ß-CD), the compound was investigated to assess the possibility of modifying the physicochemical properties (solubility, release, stability, permeability) of CTZ after complexation that are vital for subsequent formulation studies involving the said complex. Changes in FT-IR/Raman spectra, DSC thermograms and XRD diffractograms confirmed the formation of a CTZ-ß-CD system. Hydrophilic interaction chromatography with a DAD detector was employed to determine alterations of the CTZ concentration during studies following complexation. An analysis of a phase-solubility diagram of cCTZ = fcß-CD indicated a linear rise in the solubility of CTZ as the concentration of ß-CD increased. The inclusion of CTZ in a system with ß-CD significantly reduced the instability of CTZ in the presence of oxidizing factors. It was also found that regardless of the pH of the acceptor fluids used in the release studies an increase was observed in the concentration of CTZ in CD system compared to its free form. The ability to permeate artificial biological membranes manifested by CTZ after complexation was enhanced as well. In summary, CD has significant potential to mask the bitter taste of CTZ and to counter the instability induced by oxidizing factors.

The Analysis of the Physicochemical Properties of Benzocaine Polymorphs.

The study was a pioneering attempt to assess the influence of the structural polymorphism (forms I, II, III) of benzocaine on its solubility, apparent solubility, and chemical stability, which are vital parameters for preformulation and formulation work. The impact of differences in the solubility of selected polymorphs of benzocaine on their permeability through artificial biological membranes (PAMPA system) was evaluated. The polymorphs of benzocaine were obtained by means of techniques commonly used for the preparation of various pharmaceutical dosage forms: ball milling, micro milling, and cryogenic grinding, which allowed for the appearance or preservation of form III, the initial conformation of benzocaine. Ball milling resulted in the conversion of form III to I, whereas micro milling yielded form II. As a result of cryogenic grinding, form III of benzocaine was preserved. The identification of all polymorphic forms of benzocaine was confirmed via X-ray powder diffraction (PXRD) supported by FT-IR spectroscopy coupled with density functional theory (DFT) calculations. The differences in solubility, dissolution, and permeability through artificial biological membranes resulting from the polymorphic forms of benzocaine were established by using chromatographic determinations. Accelerated stability tests indicated that all polymorphic forms were chemically stable at a required level.

The Radiostability of Meropenem Trihydrate in Solid State.

The influence of ionising radiation on the physicochemical properties of meropenem trihydrate in solid state was studied for doses of e-beam radiation: 25 kGy and 400 kGy. In the first part of our studies, we evaluated the possibility of applying radiosterilization to obtain sterile meropenem. No changes for meropenem irradiated with a dose of 25 kGy, the dose required to attain sterility, was confirmed in the results of spectroscopic (FT-IR), thermal (DSC, TGA) and X-ray powder diffraction (XRPD) studies. The radiation dose of 25 kGy produces no more than about 1500 ppm of radical defects. The chromatographic studies of irradiated meropenem in solutions did not show any chemical degradation. Moreover, the antimicrobial activity of meropenem irradiated with the dose of 25 kGy was unchanged. Based on the received results, we can conclude that radiostelization is a promising, alternative method for obtaining sterile meropenem. In the second part of the research, meropenem was exposed to e-beam radiation at the 400 kGy dose rate. It was confirmed, that reducing of antimicrobial activity could be connected with the degradation of ß-lactam ring and changes in the trans-hydroxyethyl group. Apart from chemical changes, changes in the physical stability of irradiated meropenem (400 kGy) was also observed.

Solid-state stability studies of crystal form of tebipenem.

The aim of this study was to determine the kinetic and thermodynamic parameters of tebipenem degradation in the solid state. The process was analyzed based on the results obtained by a high performance liquid chromatography (HPLC) method using ultraviolet diode-array detector (DAD)/electrospray ionization tandem mass spectrometry (Q-TOF-MS/MS), Fourier transform infrared spectroscopy (FT-IR) and Raman spectroscopic (RS) studies. In dry air, the degradation of tebipenem was a first-order reaction depending on the substrate concentration while at an increased relative air humidity tebipenem was degraded according to the kinetic model of autocatalysis. The thermodynamic parameters: energy of activation (Ea), enthalpy (ΔH(≠a)) and entropy (ΔS(≠a)) of tebipenem degradation were calculated. Following a spectroscopic analysis of degraded samples of tebipenem, a cleavage of the ß-lactam bond was proposed as the main degradation pathway, next confirmation using HPLC-Q-TOF-MS/MS method.

Sweeteners Show a Plasticizing Effect on PVP K30-A Solution for the Hot-Melt Extrusion of Fixed-Dose Amorphous Curcumin-Hesperetin Solid Dispersions.

The co-administration of curcumin and hesperetin might be beneficial in terms of neuroprotective activity; therefore, in this study, we attempted to develop a fixed-dose formulation comprising these two compounds in an amorphous state. The aim of obtaining an amorphous state was to overcome the limitations of the low solubility of the active compounds. First, we assessed the possibility of using popular sweeteners (erythritol, xylitol, and sorbitol) as plasticizers to reduce the glass transition temperature of PVP K30 to prepare the polymer-excipient blends, which allowed the preparation of amorphous solid dispersions via hot-melt extrusion at a temperature below the original glass transition of PVP K30. Erythritol proved to be the superior plasticizer. Then, we focused on the development of fixed-dose amorphous solid dispersions of curcumin and hesperetin. Powder X-ray diffraction and thermal analysis confirmed the amorphous character of dispersions, whereas infrared spectroscopy helped to assess the presence of intermolecular interactions. The amorphous state of the produced dispersions was maintained for 6 months, as shown in a stability study. Pharmaceutical parameters such as dissolution rate, solubility, and in vitro permeability through artificial membranes were evaluated. The best improvement in these features was noted for the dispersion, which contained 15% of the total content of the active compounds with erythritol used as the plasticizer.

Prebiotic Systems Containing Anthocyanin-Rich Pomegranate Flower Extracts with Antioxidant and Antidiabetic Effects.

Pomegranate flower extract, rich in anthocyanins, demonstrates beneficial health-promoting properties such as an anti-diabetic and antioxidant effect, among others. However, the potential health-promoting properties may be hindered by the low stability of anthocyanins. Therefore, the aim of our study was to assess whether stabilizing carriers, namely HP-γ-cyclodextrin (HP-γ-CD), α-cyclodextrin (α-CD), Methyl-ß-cyclodextrin (Me-ß-CD), Inulin (Inu) and Arabic gum (AGu) affect the antioxidant and antidiabetic activity of lyophilized pomegranate flower extract, how they influence stability, release profile, and whether the systems exhibit prebiotic activity. Interactions between pomegranate flower extract and these factors were analyzed using FT-IR. The structures were examined through microscopic imaging while for the prepared prebiotic systems, antidiabetic activity was determined and confirmed by the inhibition of α-amylase and α-glucosidase; antioxidant activity was expressed by DPPH and CUPRAC assays. The content of pelargonidin-3,5-glucoside in these systems was assessed using the HPLC method. The release profiles of pelargonidin-3,5-glucoside were examined in a medium at pH = 6.8 and pH = 1.2, and the stability was assessed after subjecting the systems to high temperatures (T = 90 °C). The prebiotic potential was evaluated for 10 prebiotic bacterial strains (Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus brevis Lactobacillus rhamnosus gg, Lactobacillus reuteri, Pediococcus pentosaceus, Lactococcus lactis, Lactobacillus fermentum lf, Streptococcus thermophilus). As a result of the conducted research, better functionalities of the obtained systems containing Pomegranate flower extract were proven in terms of prebiotic and antidiabetic effects. The obtained delivery systems for pelargonidin-3,5-glucoside allow for better use of its health-promoting effects.

3D-Printed Chitosan-Based Scaffolds with Scutellariae baicalensis Extract for Dental Applications.

The plant material Scutellariae baicalensis radix, which is rich in flavones (baicalin), possesses antibacterial, antifungal, antioxidant, and anti-inflammatory properties. This work aimed to develop a 3D-printed chitosan-based hydrogel rich in Scutellariae baicalensis extract as an innovative approach for the personalized treatment of periodontal diseases. Chitosan-based hydrogels were prepared, and the printability of the prepared hydrogels was determined. The hydrogel with 2.5% w/v of high molecular-weight chitosan (CS), 2% w/v gelatin (Gel), and 10% w/w of extract (Ex) presented the best printability, producing smooth and uniform scaffolds. It was proved that the CS/Gel/Ex hydrogel was stabilized by hydrogen bonds and remained in amorphous dispersion in the 3D-printed structures (confirmed by ATR-FTIR and XRPD). Due to the amorphization of the active substance, a significant increase in the release of baicalin in vitro was observed. It was demonstrated that there was an initial burst release and a continuous release profile (n = 3). Higuchi kinetic was the most likely baicalin release kinetic. The second fit, the Korsmeyer-Peppas kinetics model, showed coupled diffusion of the active ingredient in the hydrated matrix and polymer relaxation regulated release, with n values ranging from 0.45 to 0.89. The anti-inflammatory properties of 3D-printed scaffolds were assessed as the ability to inhibit the activity of the hyaluronidase enzyme. Activity was assessed as IC50 = 63.57 ± 4.98 mg hydrogel/mL (n = 6). Cytotoxicity tests demonstrated the biocompatibility of the material. After 24 h of exposure to the 2.5CS/2Gel/10Ex scaffold, fibroblasts migrated toward the scratch, closed the "wound" by 97.1%, and significantly accelerated the wound healing process. The results render the 3D-printed CS/Gel/extract scaffolds as potential candidates for treating periodontal diseases.

Electrospun Nanofibers with Pomegranate Peel Extract as a New Concept for Treating Oral Infections.

Pomegranate peel extract is known for its potent antibacterial, antiviral, antioxidant, anti-inflammatory, wound healing, and probiotic properties, leading to its use in treating oral infections. In the first stage of this work, for the first time, using the Design of Experiment (DoE) approach, pomegranate peel extract (70% methanol, temperature 70 °C, and three cycles per 90 min) was optimized and obtained, which showed optimal antioxidant and anti-inflammatory properties. The optimized extract showed antibacterial activity against oral pathogenic bacteria. The second part of this study focused on optimizing an electrospinning process for a combination of polycaprolactone (PCL) and polyvinylpyrrolidone (PVP) nanofibers loaded with the optimized pomegranate peel extract. The characterization of the nanofibers was confirmed by using SEM pictures, XRPD diffractograms, and IR-ATR spectra. The composition of the nanofibers can control the release; in the case of PVP-based nanofibers, immediate release was achieved within 30 min, while in the case of PCL/PVP, controlled release was completed within 24 h. Analysis of the effect of different scaffold compositions of the obtained electrofibers showed that those based on PCL/PVP had better wound healing potential. The proposed strategy to produce electrospun nanofibers with pomegranate peel extract is the first and innovative approach to better use the synergy of biological action of active compounds present in extracts in a patient-friendly pharmaceutical form, beneficial for treating oral infections.

Electrospun Nanofibers Loaded with Marigold Extract Based on PVP/HPßCD and PCL/PVP Scaffolds for Wound Healing Applications.

Marigold flower is a traditionally used plant material topically applied on the skin due to its anti-inflammatory properties and antibacterial activity. This potential of action justifies the implementation of marigold extract in nanofiber scaffolds based on poly-vinylpyrrolidone/hydroxypropyl-ß-cyclodextrin (PVP/HPßCD) and polycaprolactone/polyvinylpyrrolidone (PCL/PVP) obtained by electrospinning for wound treatment. Using SEM, the morphology of electrospun scaffolds showed a fiber diameter in the range of 298-527 nm, with a uniform and bead-free appearance. ATR-FTIR spectroscopy confirmed the presence of marigold extracts in nanofibrous scaffolds. The composition of the nanofibers can control the release; in the case of PVP/HPßCD, immediate release of 80% of chlorogenic acid (an analytical and functional marker for marigold extract) was achieved within 30 min, while in the case of PCL/PVP, the controlled release was achieved within 24 h (70% of chlorogenic acid). All systems showed weak antibacterial activity against skin and wound-infecting bacteria Staphylococcus aureus (MIC 100 mg/mL), and Pseudomonas aeruginosa (MIC 200 mg/mL) and yeasts Candida albicans (MIC 100 mg/mL). Analysis of the effect of different scaffold compositions of the obtained electrofibers showed that those based on PCL/PVP had better wound healing potential. The scratch was closed after 36 h, compared to the 48 h required for PVP/HPßCD. Overall, the study shows that scaffolds of PCL/PVP nanofibers loaded with classic marigold extract have the best potential as wound dressing materials because of their ability to selectively modulate inflammation (via inhibition of hyaluronidase enzyme) and supportive antimicrobial properties, thereby aiding in the early stages of wound healing and repair.