Self-Nanoemulsion Intrigues the Gold Phytopharmaceutical Chrysin: In Vitro Assessment and Intrinsic Analgesic Effect.

Chrysin is a natural flavonoid with a wide range of bioactivities. Only a few investigations have assessed the analgesic activity of chrysin. The lipophilicity of chrysin reduces its aqueous solubility and bioavailability. Hence, self-nanoemulsifying drug delivery systems (SNEDDS) were designed to overcome this problem. Kollisolv GTA, Tween 80, and Transcutol HP were selected as oil, surfactant, and cosurfactant, respectively. SNEDDS A, B, and C were prepared, loaded with chrysin (0.1%w/w), and extensively evaluated. The optimized formula (B) encompasses 25% Kollisolv GTA, 18.75% Tween 80, and 56.25% Transcutol HP was further assessed. TEM, in vitro release, and biocompatibility towards the normal oral epithelial cell line (OEC) were estimated. Brain targeting and acetic acid-induced writhing in a mouse model were studied. After testing several adsorbents, powdered SNEDDS B was formulated and evaluated. The surfactant/cosurfactant (S/CoS) ratio of 1:3 w/w was appropriate for the preparation of SNEDDS. Formula B exhibited instant self-emulsification, spherical nanoscaled droplets of 155.4 ± 32.02 nm, and a zeta potential of - 12.5 ± 3.40 mV. The in vitro release proved the superiority of formula B over chrysin suspension (56.16 ± 10.23 and 9.26 ± 1.67%, respectively). The biocompatibility of formula B towards OEC was duplicated (5.69 ± 0.03 µg/mL). The nociceptive pain was mitigated by formula B more efficiently than chrysin suspension as the writhing numbers reduced from 8.33 ± 0.96 to 0 after 60 min of oral administration. Aerosil R972 was selected as an adsorbent, and its chemical compatibility was confirmed. In conclusion, our findings prove the therapeutic efficacy of chrysin self-nanoemulsion as a potential targeting platform to combat pain.

Enhanced oral delivery of hesperidin-loaded sulfobutylether-ß-cyclodextrin/chitosan nanoparticles for augmenting its hypoglycemic activity: in vitro-in vivo assessment study.

Hesperidin (Hsd), a bioactive phytomedicine, experienced an antidiabetic activity versus both Type 1 and Type 2 Diabetes mellitus. However, its intrinsic poor solubility and bioavailability is a key challenging obstacle reflecting its oral delivery. From such perspective, the purpose of the current study was to prepare and evaluate Hsd-loaded sulfobutylether-ß-cyclodextrin/chitosan nanoparticles (Hsd/CD/CS NPs) for improving the hypoglycemic activity of the orally administered Hsd. Hsd was first complexed with sulfobutylether-ß-cyclodextrin (SBE-ß-CD) and the complex (CX) was found to be formed with percent complexation efficiency and percent process efficiency of 50.53 ± 1.46 and 84.52 ± 3.16%, respectively. Also, solid state characterization of the complex ensured the inclusion of Hsd inside the cavity of SBE-ß-CD. Then, Hsd/CD/CS NPs were prepared using the ionic gelation technique. The prepared NPs were fully characterized to select the most promising one (F1) with a homogenous particle size of 455.7 ± 9.04 nm, a positive zeta potential of + 32.28 ± 1.12 mV, and an entrapment efficiency of 77.46 ± 0.39%. The optimal formula (F1) was subjected to further investigation of in vitro release, ex vivo intestinal permeation, stability, cytotoxicity, and in vivo hypoglycemic activity. The results of the release and permeation studies of F1 manifested a modulated pattern between Hsd and CX. The preferential stability of F1 was observed at 4 ± 1 °C. Also, the biocompatibility of F1 with oral epithelial cell line (OEC) was retained up to a concentration of 100 µg/mL. After oral administration of F1, a noteworthy synergistic hypoglycemic effect was recorded with decreased blood glucose level until the end of the experiment. In conclusion, Hsd/CD/CS NPs could be regarded as a hopeful oral delivery system of Hsd with enhanced antidiabetic activity.

Carvacrol-Loaded Phytosomes for Enhanced Wound Healing: Molecular Docking, Formulation, DoE-Aided Optimization, and in vitro/in vivo Evaluation.

Background: Despite recent advances in wound healing products, phytochemicals have been considered promising and attractive alternatives. Carvacrol (CAR), a natural phenolic compound, has been reported to be effective in wound healing. Purpose: This work endeavored to develop novel CAR-loaded phytosomes for the enhancement of the wound healing process. Methods: Molecular docking was performed to compare the affinities of the different types of phospholipids to CAR. Phytosomes were prepared by three methods (thin-film hydration, cosolvency, and salting out) using Lipoid S100 and Phospholipon 90H with three levels of saturation percent (0%, 50%, and 100%), and three levels of phospholipid molar percent (66.67%, 75%, and 80%). The optimization was performed using Design Expert where particle size, polydispersity index, and zeta potential were chosen as dependent variables. The optimized formula (F1) was further investigated regarding entrapment efficiency, TEM, 1H-NMR, FT-IR, DSC, X-RD, in vitro release, ex vivo permeation, and stability. Furthermore, it was incorporated into a hydrogel formulation, and an in vivo study was conducted to investigate the wound-healing properties of F1. Results: F1 was chosen as the optimized formula prepared via the thin-film hydration method with a saturation percent and a phospholipid molar percent of zero and 66.67, respectively. TEM revealed the spherical shape of phytosomal vesicles with uniform size, while the results of 1H-NMR, FT-IR, DSC, and X-RD confirmed the formation of the phytosomal complex. F1 demonstrated a higher in vitro release and a slower permeation than free CAR. The wound area of F1-treated animals showed a marked reduction associated with a high degree of collagen fiber deposition and enhanced cellular proliferation. Conclusion: F1 can be considered as a promising remedy for the enhancement of wound healing and hence it would be hoped to undergo further investigation.

Crucial Role of PLGA Nanoparticles in Mitigating the Amiodarone-Induced Pulmonary Toxicity.

BACKGROUND: Amiodarone (AMD) is a widely used anti-arrhythmic drug, but its administration could be associated with varying degrees of pulmonary toxicity. In attempting to circumvent this issue, AMD-loaded polymeric nanoparticles (AMD-loaded NPs) had been designed. MATERIALS AND METHODS: AMD was loaded in NPs by the nanoprecipitation method using two stabilizers: bovine serum albumin and Kolliphor® P 188. The physicochemical properties of the AMD-loaded NPs were determined. Among the prepared NPs, two ones were selected for further investigation of spectral and thermal analysis as well as morphological properties. Additionally, in vitro release patterns were studied and kinetically analyzed at different pH values. In vitro cytotoxicity of an optimized formula (NP4) was quantified using A549 and Hep-2 cell lines. In vivo assessment of the pulmonary toxicity on Sprague Dawley rats via histopathological and immunohistochemical evaluations was applied. RESULTS: The developed NPs achieved a size not more than 190 nm with an encapsulation efficiency of more than 88%. Satisfactory values of loading capacity and yield were also attained. The spectral and thermal analysis demonstrated homogeneous entrapment of AMD inside the polymeric matrix of NPs. Morphology revealed uniform, core-shell structured, and sphere-shaped particles with a smooth surface. Furthermore, the AMD-loaded NPs exhibited a pH-dependent and diffusion-controlled release over a significant period without an initial burst effect. NP4 demonstrated a superior cytoprotective efficiency by diminishing cell death and significantly increasing the IC50 by more than threefold above the pure AMD. Also, NP4 ameliorated AMD-induced pulmonary damage in rats. Significant downregulation of inflammatory mediators and free radicle production were noticed in the NP4-treated rats. CONCLUSION: The AMD-loaded NPs could ameliorate the pulmonary injury induced by the pure drug moieties. Cytoprotective, anti-fibrotic, anti-inflammatory, and antioxidant properties were presented by the optimized NPs (NP4). Future studies may be built on these findings for diminishing AMD-induced off-target toxicities.

Appraisal of amiodarone-loaded PLGA nanoparticles for prospective safety and toxicity in a rat model.

AIMS: Amiodarone (AM) is a highly efficient drug for arrhythmias treatment, but its extra-cardiac adverse effects offset its therapeutic efficacy. Nanoparticles (NPs)-based delivery system could provide a strategy to allow sustained delivery of AM to the myocardium and reduction of adverse effects. The primary purpose was to develop AM-loaded NPs and explore their ameliorative effects versus off-target toxicities. MATERIALS AND METHODS: Polymeric NPs were prepared using poly lactic-co-glycolic acid and their physicochemical properties were characterized. Animal studies were conducted using a rat model to compare exposure to AM versus that of the AM-loaded NPs. Biochemical evaluation of liver enzymes, lipid profile, and thyroid hormones was achieved. Besides, histopathological changes in liver and lung were studied. KEY FINDINGS: Under optimal experimental conditions, the AM-loaded NPs had a size of 186.90 nm and a negative zeta potential (-14.67 mV). Biochemical evaluation of AM-treated animal group showed a significant increase in cholesterol, TG, LDL, T4, and TSH levels (ρ < 0.05). Remarkably, the AM-treated group exhibited a significant increase of liver enzymes (ρ < 0.05) coupled with an obvious change in liver architecture. The AM-loaded NPs displayed a reduction of liver damage and enzyme levels. Lung sections of the AM-treated group demonstrated thickening of interalveolar septa, mononuclear cellular infiltration with congested blood vessels, and heavy collagenous fibers deposition. Conversely, less cellular infiltration and septal thickening were observed in the animal lungs treated with the AM-loaded NPs-treated. SIGNIFICANCE: Our findings demonstrate the competence of the AM-loaded NPs to open several exciting avenues for evading the AM-induced off-target toxicities.

Egyptian Propolis-Loaded Nanoparticles as a Root Canal Nanosealer: Sealing Ability and in vivo Biocompatibility.

BACKGROUND: Successful endodontic therapy is mainly governed by the satisfactory sealing ability of the applied root canal sealer. Also, tolerability of root canal structure to accommodate the presence of a sealer participates in the efficiency of the treatment. Hence, this study was aimed to extrapolate our previous one that was concerned with the preparation and evaluation of novel nature-based root canal sealers. Our current work is focused on the evaluation of sealing ability and in vivo biocompatibility. MATERIALS AND METHODS: Egyptian propolis was extracted (ProE) and encapsulated in polymeric nanoparticles (ProE-loaded NPs). Two root sealers, PE sealer and PE nanosealer, were fabricated by incorporating ProE and ProE-loaded NPs, respectively. The sealing ability of the developed sealers was tested by a dye extraction method. An in vivo biocompatibility study was conducted using a subcutaneous implantation method for two and four weeks. At the same time, a model sealer (AH Plus®) was subjected to the same procedures to enable accurate and equitable results. RESULTS: The teeth treated with PE sealer exhibited weak sealing ability which did not differ from that of unfilled teeth. PE nanosealer enhanced the sealing ability similarly to the model sealer with minimal apical microleakage. Studying in vivo biocompatibility indicated the capability of the three tested sealers to induce cell proliferation and tissue healing. However, PE nanosealer had superior biocompatibility, with higher potential for cell regeneration and tissue proliferation. CONCLUSION: PE nanosealer can be presented as an innovative root canal sealer, with enhanced sealing ability as well as in vivo biocompatibility. It can be applied as a substitute for the currently available sealers that demonstrate hazardous effects.

Design, Evaluation And Antimicrobial Activity Of Egyptian Propolis-Loaded Nanoparticles: Intrinsic Role As A Novel And Naturally Based Root Canal Nanosealer.

BACKGROUND: Propolis is a unique natural adhesive product collected by honeybees. It contains a diversity of bioactive compounds with reported functional properties such as antioxidants, antibacterial, antifungal, anti-inflammatory, antiviral and anticancer activity. Dental caries is a worldwide problem that caused by microbial growth usually progress from tooth enamel to the underlying pulpal tissues and root canal. This situation could be controlled by a sequence of steps to remove microorganisms and fill root canal with a suitable long-lasting root canal sealer. Unfortunately, leachable and degradation products of the currently used sealers compromised their antimicrobial activity by inflammatory modulation associated with irritation and toxicity of periapical tissues. MATERIALS AND METHODS: Hence, propolis was selected to be designed as a natural root canal sealer due to its amazing functional properties. Moreover, its handling properties were enhanced and potentiated by its incorporation in polymeric nanoparticles (NPs). Frist, propolis was collected, extracted and analyzed for its bioactive compounds. After that, propolis-loaded NPs of PLGA (ProE-loaded NPs) were developed and fully characterized regarding physicochemical properties, in vitro release and in vitro cytotoxicity. Then, root canal sealers were fabricated and assayed for their antimicrobial activity. Both cytotoxicity and antimicrobial activity were compared to those of a model sealer; AH Plus®. RESULTS: The results revealed that spherical nanoscopic NPs with narrow size distribution were obtained. ProE-loaded NPs exhibited accepted entrapment efficiency (>80) and prolonged release. In vitro cytotoxicity study confirmed the safety of ProE-loaded NPs. Also, the developed sealers showed antimicrobial activity versus bacterial strains of Enterococcus faecalis and Streptococcus mutans and antifungal activity against Candida albicans. CONCLUSION: ProE-loaded NPs could be incorporated in and represented as a root canal sealer with prolonged release and enhanced cytocompatibility as well as antimicrobial activities.