Formulation Development of Mucoadhesive Microparticle-Laden Gels for Oral Mucositis: An In Vitro and In Vivo Study

In order to relieve pain due to oral mucositis, we attempted to develop mucoadhesive microparticles containing indomethacin (IM) and gel preparations with IM microparticles that can be applied to the oral cavity. The mucoadhesive microparticles were prepared with a simple composition consisting of IM and polyvinyl alcohol (PVA). Two kinds of PVA with different block properties were used, and microparticles were prepared by heating-filtration and mixing-drying. From the X-ray powder diffraction patterns, differential scanning calorimetry thermograms, and morphological features of the IM microparticles, IM should exist as polymorphic forms in the microparticles. Rapid drug release properties were observed in the IM microparticles. Increased drug retention was observed in IM microparticles containing PVA, and the IM-NK(50) gel, using a common block character PVA and heating-filtration, showed good long-term drug retention properties. In vivo experiments showing significantly higher drug concentrations in the oral mucosa were observed with IM microparticles prepared by heating-filtration, and the IM-NK(50) gel maintained significantly higher drug concentrations in the oral mucosa. From these results, the IM-NK(50) gel may be useful as a preparation for relieving oral mucositis pain.

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A Comparative Study of Bioceramics In Vitro and In Vivo

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.284-286.11 ◽

2005 ◽

Vol 284-286 ◽

pp. 11-14 ◽

Cited By ~ 2

Author(s):

Yang Leng ◽

Ren Long Xin ◽

Ji Yong Chen

Keyword(s):

Calcium Phosphates ◽

Glass Ceramics ◽

Octacalcium Phosphate ◽

Rabbit Muscle ◽

In Vivo Experiments ◽

Transmission Electron ◽

Diffraction Patterns ◽

Dental Applications

Bioactive calcium phosphate (Ca-P) formation in bioceramics surfaces in simulated body fluid (SBF) and in rabbit muscle sites was investigated. The examined bioceamics included most commonly used bioglass®, A-W glass-ceramics and calcium phosphates in orthopedic and dental applications. The Ca-P cyrstal structures were examined with single crystal diffraction patterns in transmission electron microscopy, which reduced possibility of misidentifying Ca-P phases. The experimental results show that capability of Ca-P formation considerably varied among bioceramics, particularly in vivo. Octacalcium phosphate (OCP) was revealed on the all types of bioceramics in vitro and in vivo experiments. This work leads us to rethink how to evaluate bioactivity of bioceramics and other orthopedic materials which exhibit capability of osteoconduction by forming direct bonding with bone.

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Development and Characterization of the Neuroregenerative Xanthohumol C/Hydroxypropyl-β-cyclodextrin Complex Suitable for Parenteral Administration

Planta Medica ◽

10.1055/a-1013-1276 ◽

2019 ◽

Vol 85 (16) ◽

pp. 1233-1241

Author(s):

Michael Kirchinger ◽

Lara Bieler ◽

Julia Tevini ◽

Michael Vogl ◽

Elisabeth Haschke-Becher ◽

...

Keyword(s):

Water Solubility ◽

Pharmaceutical Research ◽

Water Soluble ◽

Complexing Agents ◽

Cyclodextrin Complex ◽

Scanning Calorimetry ◽

In Vivo Experiments ◽

Strong Candidate

AbstractThe chroman-like chalcone Xanthohumol C, originally found in hops, was demonstrated to be a potent neuroregenerative and neuroprotective natural product and therefore constitutes a strong candidate for further pharmaceutical research. The bottleneck for in vivo experiments is the low water solubility of this chalcone. Consequently, we developed and validated a suitable formulation enabling in vivo administration. Cyclodextrins were used as water-soluble and nontoxic complexing agents, and the complex of Xanthohumol C and 2-hydroxypropyl-β-cyclodextrin was characterized using HPLC, HPLC-MS, NMR, and differential scanning calorimetry. The water solubility of Xanthohumol C increases with increasing concentrations of cyclodextrin. Using 50 mM 2-hydroxypropyl-β-cyclodextrin, solubility was increased 650-fold. Furthermore, in vitro bioactivity of Xanthohumol C in free and complexed form did not significantly differ, suggesting the release of Xanthohumol C from 2-hydroxypropyl-β-cyclodextrin. Finally, a small-scaled in vivo experiment in a rat model showed that after i. p. administration of the complex, Xanthohumol C can be detected in serum, the brain, and the cerebrospinal fluid at 1 and 6 h post-administration. Mean (± SD) Xanthohumol C serum concentrations after 1, 6, and 12 h were determined as 463.5 (± 120.9), 61.9 (± 13.4), and 9.3 (± 0.8) ng/mL upon i. v., and 294.3 (± 22.4), 45.5 (± 0.7), and 13 (± 1.0) ng/mL after i. p. application, respectively. Accordingly, the formulation of Xanthohumol C/2-hydroxypropyl-β-cyclodextrin is suitable for further in vivo experiments and further pharmaceutical research aiming for the determination of its neuroregenerative potential in animal disease models.

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Efficacious Treatment of Experimental Leishmaniasis with Amphotericin B-Arabinogalactan Water-Soluble Derivatives

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.43.9.2209 ◽

1999 ◽

Vol 43 (9) ◽

pp. 2209-2214 ◽

Cited By ~ 33

Author(s):

Jacob Golenser ◽

Shoshana Frankenburg ◽

Tirtsa Ehrenfreund ◽

Abraham J. Domb

Keyword(s):

Amphotericin B ◽

Leishmania Major ◽

Water Soluble ◽

In Vivo Experiments ◽

Drug Concentrations ◽

Efficacious Treatment ◽

Lipid Formulations ◽

Established Infection

ABSTRACT In this study, we tested the efficacy of amphotericin B (AmB)-arabinogalactan (AmB-AG) conjugates for the treatment of experimental leishmaniasis. Chemical conjugation of AmB to a water-soluble, biodegradable, and biocompatible polymer could present many advantages over presently available AmB formulations. Two conjugates were tested, a reduced (rAmB-AG) form and an unreduced (uAmB-AG) form. In vitro, the drug concentrations which lower the values of parasites (for promastigotes) or infected macrophages (for amastigotes) to 50% of the untreated values (ED50s) of uAmB-AG and rAmB-AG were 0.19 and 0.34 μg/ml, respectively, forLeishmania major promastigotes and 0.17 and 0.31 μg/ml, respectively, for amastigotes. The effect on Leishmania infantum-infected macrophages was more marked, with ED50s of 0.035 μg/ml for rAmB-AG and 0.027 μg/ml for uAmB-AG. In in vivo experiments, BALB/c mice injected with L. major were treated from day 2 onwards on alternate days for 2 weeks. Both conjugates, as well as liposomal AmB (all at 6 mg/kg of body weight) and Fungizone (1 mg/kg), significantly delayed the appearance of lesions compared to that in untreated mice. In addition, both conjugates, but not liposomal AmB, were significantly more effective than Fungizone. Subcutaneous injection of the conjugates (6 mg/kg) was significantly more effective than liposomal AmB in delaying the appearance of lesions. Higher AmB concentrations of up to 12 mg/kg could be administered by this route. When an established infection was treated, uAmB-AG was somewhat more effective than liposomal AmB. In summary, water-soluble polymeric AmB derivatives were found effective and safe for the treatment of leishmanial infections. The conjugates, which are stable and can be produced relatively cheaply (compared to lipid formulations), can be used in the future for the treatment of leishmaniasis infections.

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Applying Supercritical Fluid Technology to Prepare Ibuprofen Solid Dispersions with Improved Oral Bioavailability

Pharmaceutics ◽

10.3390/pharmaceutics11020067 ◽

2019 ◽

Vol 11 (2) ◽

pp. 67 ◽

Cited By ~ 5

Author(s):

Fei Han ◽

Wei Zhang ◽

Ying Wang ◽

Ziyue Xi ◽

Lu Chen ◽

...

Keyword(s):

Binding Energy ◽

Supercritical Fluid ◽

Solid Dispersions ◽

Physical Stability ◽

In Vitro Dissolution ◽

Scanning Calorimetry ◽

Drug Concentrations ◽

Supercritical Fluid Technology

In this study, supercritical fluid (SCF) technology was applied to prepare reliable solid dispersions of pharmaceutical compounds with limited bioavailability using ibuprofen (IBU) as a model compound. Solid-state characterization of the dispersions was conducted by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The PXRD and DSC results suggested that the amorphous form of IBU was maintained in the solid dispersions. Furthermore, in vitro dissolution and in vivo pharmacokinetic (PK) studies in rats were also performed. The dissolution performance of the SCF-prepared IBU dispersions was significantly improved compared to that of the physical mixtures of crystalline IBU and a polymer. In addition, the PK results revealed that the SCF-prepared IBU dispersions produced remarkably high blood drug concentrations (both the AUC and Cmax) and a rapid absorption rate (Tmax). Finally, molecular modeling was used to evaluate the binding energy of interactions between IBU and the polymers. The negative binding energy suggests a relatively stable system. Hence, SCF technology can be used as a very effective approach to prepare IBU solid dispersions with good physical stability and enhanced in vitro and in vivo performance.

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In vitro activity of six antiviral drugs against equid alphaherpesvirus type 1 indicates ganciclovir as promising drug for in vivo studies

Ciência Rural ◽

10.1590/0103-8478cr20180085 ◽

2018 ◽

Vol 48 (12) ◽

Cited By ~ 2

Author(s):

Amanda Lovato de Oliveira ◽

Juliana Felipetto Cargnelutti ◽

Ana Paula Gnocato Mortari ◽

Eduardo Furtado Flores ◽

Rudi Weiblen

Keyword(s):

Specific Treatment ◽

Vitro Activity ◽

In Vivo Studies ◽

In Vitro Activity ◽

In Vivo Experiments ◽

Drug Concentrations ◽

Viral Plaque

ABSTRACT: Equid alphaherpesvirus type 1 (EHV-1) is distributed worldwide and is a major agent of abortion, respiratory and neurological disease in horses. No specific treatment is available for EHV-1 infection, yet the potential of antiviral therapy has been explored. In this study we investigated the in vitro activity of Acyclovir, Ganciclovir, Foscarnet, Famciclovir, Vidarabina and Cidofovir against EHV-1. For this, the MTT test was performed, in which all the tested drugs showed no toxicity up to 200μg/mL. Subsequently, different drug concentrations were submitted to viral plaque reduction assays in cell culture. The selectivity index (SI) of the compounds was determined using the cytotoxic concentration for 50% of cells (CC50), obtained by MTT, and effective drug concentration to inhibit by 50% the number of viral plaques (EC50). Ganciclovir (SI: 490; EC50: 1.9 μg/mL) was the most efficient and safest drug against EHV-1, followed by Cidofovir (SI: 150, EC50: 5.7μg/mL), Acyclovir (SI: 37.4, EC50: 22.2μg/mL), Famciclovir (SI: 25.1, EC50: 24.5μg/mL), Vidarabine (SI: 12.2, EC50: 40.9μg/mL) and Foscarnet (SI: 6.9, EC50: 49.5 μg/mL), respectively. These results indicated that Ganciclovir (followed by Cidofovir), is a promising candidate for use in in vivo experiments.

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Preparation of Curcumin-Eudragit® E PO Solid Dispersions with Gradient Temperature through Hot-Melt Extrusion

Molecules ◽

10.3390/molecules26164964 ◽

2021 ◽

Vol 26 (16) ◽

pp. 4964

Author(s):

Wenling Fan ◽

Xiaotong Zhang ◽

Wenjing Zhu ◽

Xinyi Zhang ◽

Liuqing Di

Keyword(s):

Solid Dispersions ◽

Hot Melt Extrusion ◽

Solubility Parameters ◽

Sprague Dawley ◽

Melt Extrusion ◽

Scanning Calorimetry ◽

In Vivo Experiments ◽

Hot Melt

Hot-melt extrusion (HME) has great advantages for the preparation of solid dispersion (SD), for instance, it does not require any organic solvents. Nevertheless, its application to high-melting-point and thermosensitive drugs has been rarely reported. In this study, thermally unstable curcumin (Cur) was used as a drug model. The HME process was systematically studied by adjusting the gradient temperature mode and residence time, with the content, crystallinity and dissolution of Cur as the investigated factors. The effects of barrel temperature, screw speed and cooling rate on HME were also examined. Solubility parameters and the Flory–Huggins method were used to evaluate the miscibility between Cur and carriers. Differential scanning calorimetry, X-ray diffraction, Fourier transform infrared spectroscopy, equilibrium solubility and in vitro and in vivo experiments were used to characterize and evaluate the results. An amorphous Cur SD was successfully obtained, increasing the solubility and release of Cur. In the optimal process, the mass ratio of Cur to Eudragit® E PO (EPO) was 1:4 and the barrel temperature was set at a gradient heating mode (130 °C–135 °C–140 °C–145 °C–150 °C–155 °C–160 °C) at 100 rpm. Related pharmacokinetic test results also showed the improved bioavailability of the drug in rats. In a pharmacodynamic analysis of Sprague–Dawley rats, the Cmax and the bioavailability of the Cur-EPO SD were 2.6 and 1.5 times higher than those of Cur, respectively. The preparation of the amorphous SD not only provided more solubility but also improved the bioavailability of Cur, which provides an effective way to improve the bioavailability of BCS II drugs.

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Formulation Development of Mouth Dissolving Film of Etoricoxib for Pain Management

Advances in Pharmaceutics ◽

10.1155/2015/702963 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 5

Author(s):

K. Senthilkumar ◽

C. Vijaya

Keyword(s):

Pain Management ◽

Immediate Release ◽

Rapid Onset ◽

Ease Of Use ◽

Taste Masking ◽

Formulation Development ◽

Scanning Calorimetry ◽

Onset Of Action

Etoricoxib is a potent, orally active, and highly selective COX-2 inhibitor that exhibits anti-inflammatory, analgesic, and antipyretic activities. The present research was undertaken to develop mouth dissolving films of etoricoxib to have rapid onset of action. Mouth dissolving film (MDF) is a better alternate to oral disintegrating tablets due to its novelty, ease of use, and the consequent patient compliance. Solubility enhancement and taste masking of etoricoxib were the two challenges solved by formulating drug-inclusion complex with beta-cyclodextrin (BCD). MDF prepared by solvent casting etoricoxib-BCD complex along with HPMC as film forming polymer was found to possess desirable physicomechanical properties. In vitro release of etoricoxib from MDF in simulated salivary fluid and 0.1 N HCl was more than 95% within 2 minutes. Taste masking and in vivo disintegration were in acceptable range as assessed by human volunteers. Etoricoxib MDF was further characterized by differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy. The index of analgesia shown by etoricoxib MDF was comparable to that of immediate release tablets (100% activity within 40 minutes) in animal studies. Conclusively, the present study documents the development of a commercially viable formula for an MDF of etoricoxib with rapidity in pain management.

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Totally Biodegradable and Osteoconductive Composite Material Consisting of Polyhydroxybutyrate and Tricalcium Phosphate for Bone Tissue Repair

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.47-50.1395 ◽

2008 ◽

Vol 47-50 ◽

pp. 1395-1398

Author(s):

Ya Liu ◽

Min Wang

Keyword(s):

Composite Material ◽

Bone Tissue ◽

Tricalcium Phosphate ◽

Tissue Repair ◽

Scanning Calorimetry ◽

Electron Microscopic ◽

In Vivo Experiments ◽

Composite Production

Totally biodegradable and osteoconductive composite material consisting of polyhydroxybutyrate (PHB) and β-tricalcium phosphate (β-TCP) was manufactured for bone tissue repair. The composite production process was optimized with the help of differential scanning calorimetry (DSC) analyses. Thermogravimetric analyses (TGA) indicated that intended compositions for TCP/PHB composite could be achieved through this manufacturing route. Scanning electron microscopic (SEM) examinations revealed that TCP/PHB composite containing up to 40 vol.% of β-TCP had satisfactory distribution of micron-sized TCP particles in the composite. The good-quality composite will be further investigated in in vitro and in vivo experiments.

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Polyglycerol Ester-Based Low Energy Nanoemulsions with Red Raspberry Seed Oil and Fruit Extracts: Formulation Development toward Effective In Vitro/In Vivo Bioperformance

Nanomaterials ◽

10.3390/nano11010217 ◽

2021 ◽

Vol 11 (1) ◽

pp. 217

Author(s):

Ana Gledovic ◽

Aleksandra Janosevic Lezaic ◽

Ines Nikolic ◽

Marija Tasic-Kostov ◽

Jelena Antic-Stankovic ◽

...

Keyword(s):

Seed Oil ◽

Human Keratinocytes ◽

Formulation Development ◽

Red Raspberry ◽

Scanning Calorimetry ◽

Visual Appearance ◽

Fruit Extracts ◽

Polyglycerol Ester

This study focuses on the development of biocompatible oil-in-water (O/W) nanoemulsions based on polyglycerol esters, as promising carriers for natural actives: red raspberry seed oil—RO and hydro-glycolic fruit extracts from red raspberry—RE and French oak—FE. Nanoemulsions were obtained via phase inversion composition (PIC) method at room temperature by dilution of microemulsion phase, confirmed by visual appearance, percentage of transmittance, microscopic, rheological and differential scanning calorimetry (DSC) investigations. The results have shown that the basic RO-loaded formulation could be further enriched with hydro-glycolic fruit extracts from red raspberry or French oak, while keeping a semi-transparent appearance due to the fine droplet size (Z-ave: 50 to 70 nm, PDI value ≤ 0.1). The highest antioxidant activity (~92% inhibition of the DPPH radical) was achieved in the formulation containing both lipophilic (RO) and hydrophilic antioxidants (FE), due to their synergistic effect. The nanoemulsion carrier significantly increased the selective cytotoxic effect of RO towards malignant melanoma (Fem-X) cells, compared to normal human keratinocytes (HaCaT). In vivo study on human volunteers showed satisfactory safety profiles and significant improvement in skin hydration during 2 h after application for all nanoemulsions. Therefore, polyglycerol ester-based nanoemulsions can be promoted as effective carriers for red raspberry seed oil and/or hydro-glycolic fruit extracts in topical formulations intended for skin protection and hydration.

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Induction and Differentiation of Dental Epithelium in Vivo and in Vitro

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053425 ◽

1982 ◽

Vol 40 ◽

pp. 142-145

Author(s):

E. J. Kollar

Keyword(s):

Connective Tissue ◽

Oral Mucosa ◽

Basal Lamina ◽

Functional Derivatives ◽

Specific Source ◽

Dental Epithelium ◽

Connective Tissue Stroma

The differentiation and maintenance of many specialized epithelial structures are dependent on the underlying connective tissue stroma and on an intact basal lamina. These requirements are especially stringent in the development and maintenance of the skin and oral mucosa. The keratinization patterns of thin or thick cornified layers as well as the appearance of specialized functional derivatives such as hair and teeth can be correlated with the specific source of stroma which supports these differentiated expressions.

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