Clindamycin phosphate and bone morphogenetic protein-7 loaded combined nanoparticle-graft and nanoparticle-film formulations for alveolar bone regeneration - An in vitro and in vivo evaluation.

Commonly utilized techniques for healing alveolar bone destruction such as the use of growth factors, suffering from short half-life, application difficulties, and the ability to achieve bioactivity only in the presence of high doses of growth factor. The sustained release of growth factors through a scaffold-based delivery system offers a promising and innovative tool in dentistry. Furthermore, it is suggested to guide the host response by using antimicrobials together with growth factors to prevent recovery and achieve ideal regeneration. Herein, the aim was to prepare and an in vitro - in vivo evaluation of bone morphogenetic protein 7 (BMP-7) and clindamycin phosphate (CDP) loaded polymeric nanoparticles, and their loading into the alginate-chitosan polyelectrolyte complex film or alloplastic graft to accelerate hard tissue regeneration. PLGA nanoparticles containing CDP and BMP-7, separately or together, were prepared using the double emulsion solvent evaporation technique. Through in vitro assays, it was revealed that spherical particles were homogeneously distributed in the combination formulations, and sustained release could be achieved for >12 weeks with all formulations. Also, results from the micro-CT and histopathological analyses indicated that CDP and BMP-7 loaded nanoparticle-film formulations were more effective in treatment than the nanoparticle loaded grafts.

Preparation and evaluation of clindamycin phosphate loaded chitosan/alginate polyelectrolyte complex film as mucoadhesive drug delivery system for periodontal therapy.

In this study, Clindamycin phosphate loaded adhesive polyelectrolyte complex films for local periodontal therapy were prepared with alginate and chitosan. The thickness, drug content, structure, swelling, adhesion and in vitro drug release with release kinetics of formulations were evaluated. The effects of the varying concentration and molecular weight of polymers used and the volume of the polymer solutions on the characteristics of the films were investigated. Increasing the concentration of sodium alginate in total content of polymer mixture caused to higher adhesiveness. Chitosan molecular weight also affected to adhesiveness of complex films. The release rate of drug and release kinetics was affected from the complexation. The best complexation was obtained with the three times higher concentration and volume of alginate in combination with low molecular weight chitosan. Thus polyelectrolyte films that have delayed release together with high swelling ability and adhesiveness and high drug content were formed. Due to the heterogeneous structure of complex film, the release profiles of the formulations fitted to the anomalous transport mechanism. 3D structure of the drug loaded complex film was analyzed by Micro-CT imaging in this study and it was showed that using this method would be very advantageous for further studies about the investigation of complexation than the other imaging methods in order to determine the volume and the size of the formed complexes within the structure at the same time.

In situ forming implants for the delivery of metronidazole to periodontal pockets: formulation and drug release studies.

This study was performed to obtain prolonged drug release with biodegradable in situ forming implants for the local delivery of metronidazole to periodontal pockets. The effect of polymer type (capped and uncapped PLGA), solvent type (water-miscible and water-immiscible) and the polymer/drug ratio on in vitro drug release studies were investigated. In situ implants with sustained metronidazole release and low initial burst consisted of capped PLGA and N-methyl-2-pyrolidone as solvent. Mucoadhesive polymers were incorporated into the in situ implants in order to modify the properties of the delivery systems towards longer residence times in vivo. Addition of the polymers changed the adhesiveness and increased the viscosity and drug release of the formulations. However, sustained drug release over 10 days was achievable. Biodegradable in situ forming implants are therefore an attractive delivery system to achieve prolonged release of metronidazole at periodontal therapy.

Preparation and characterization of chitosan-based spray-dried microparticles for the delivery of clindamycin phosphate to periodontal pockets.

Biodegradable spray-dried chitosan microparticles loaded with clindamycin phosphate (CDP) were formulated to deliver drugs locally into the periodontal pocket. The effects of spray dryer conditions, drug/polymer ratio, and added amounts of glutaraldehyde (GA) solution on the characterization of microparticles were investigated by determining process yield, encapsulation efficiency, particle size and size distribution, surface morphology, drug release, release kinetics, thermal analysis, and antimicrobial efficacy of formulations. Burst release was obtained for all formulations due to the water solubility of the drug, but the increased amount of chitosan decreased the drug release rates. Microparticles with a more wrinkled surface were obtained by increasing the amount of the drug. Incorporation efficiencies higher than 80% were obtained for all preparation conditions. The addition of GA caused higher viscosity of the chitosan solution, leading to larger particles with more spherical and smooth surface characteristics. However, the increased GA amount did not significantly influence the drug release. The data obtained from in vitro release experiments were best fitted to the Weibull and Higuchi models. The amorphous nature of the drug-loaded microparticles was detected by differential scanning calorimetric (DSC) thermographs. A delayed drug release of more than one week could be obtained by loading the drug into the chitosan microparticles. Antimicrobial efficacy studies reflected a positive drug release profile. These results indicate that spray-dried clindamycin-loaded microparticles with sustained antimicrobial efficacy appear to be a promising periodontal therapy for drug delivery into the periodontal pocket.

Poly (epsilon-caprolactone) microparticles containing Levobunolol HCl prepared by a multiple emulsion (W/O/W) solvent evaporation technique: effects of some formulation parameters on microparticle characteristics.

The aim of this study was to prepare poly (epsilon-caprolactone) (PCL) microparticles of Levobunolol HC1 (L-HC1) for use as an anti-glaucomatous drug to the eye. The double emulsion (W/O/W) solvent evaporation technique was used for encapsulating L-HC1 as a hydrophilic drug. The study examined the impact of different factors including the pH and volume of the external aqueous phase, the concentration of polyvinylalcohol (PVA) and Pluronic F68 (PF68) used as stabilizers and drug/polymer ratios on the characteristics of the microparticles. Scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) were used to identify the physical state of the drug and polymer. The zeta potential of the particles was also identified. Entrapment efficiency was found to be highest with a 0.5% PVA concentration and 100 mL volume of external aqueous phase at pH 12. The high efficiency was due to a reduction in the degree of drug ionization. The microparticles were spherical and appropriately sized for ophthalmic application. Drug release from the microparticles appears to consist of two components, with an initial rapid release followed by a slower stage. Drug release was slower when the microparticle was incorporated into the thermally reversible gel (Pluronic F127) in comparison to drug release from the free drug incorporated into the gel and drug release from the free microparticle.

In vitro and in vivo transdermal studies of atenolol using iontophoresis.

Matrix formulations of Eudragit E 100: NE 40D polymers (100:0, 70:30, 60:40, 50:50% w/w) with 20% w/w of triacetine and 5% w/w of atenolol were prepared by film casting method with different solvents (methanol, 2-propanol and acetone). In vitro release of atenolol from the films were studied by vertical Franz diffusion cells in HEPES buffer (pH 7.4) for 78 h. Direct currents of 0.1 and 0.5 mA/cm2 were applied for 6 h to the formulations with Ag/AgCl electrodes. Also, transdermal application for the Eudragit E 100: NE 40 D (70:30% w/w) formulation was compared by iontophoresis or oleic acid (2.5% w/v) with control group on Wistar rats. As a result, the in vitro release rate of atenolol from films were increased with iontophoresis by increasing the current density (from 0.240 to 0.424 mg/cm2 for 70:3% w/w formulation) and also increased with the amount of Eudragit NE 40D (from 0.646 to 1.30 mg/cm2 at the end of 78 h). It is obtained from the in vivo studies that oleic acid provided a higher plasma and skin concentration (0.825 mg/mL and 12.5 mg/cm2, respectively) than iontophoresis treatment (0.399 mg/mL and 1.81 mg/cm2, respectively) due to the different mechanisms. However, the results showed that iontophoresis is a good alternative for enhancing the transdermal delivery of atenolol.

Influence of aluminum tristearate and sucrose stearate as the dispersing agents on physical properties and release characteristics of Eudragit RS microspheres.

The purpose of this research was to investigate the effects of different concentrations of polymer and sucrose stearate, aluminum tristearate as dispersing agents on microsphere properties and performance. The yield values of microspheres were over the 78%, and the encapsulation efficiencies were found to be ∼735. Particle sizes of microspheres prepared with aluminum tristearate were between 76 and 448 µm, while that of the microspheres containing sucrose stearate were between 521 and 2000 µm. Morphological and physicochemical properties of microspheres were investigated by scanning electron micrography and differential scanning calorimetry (DSC). DSC analysis indicated that verapamil hydrochloride formed a solid solution with acrylic polymers. In vitro release studies were performed using the flow-through cell method. While ∼80% of drug was released from the microspheres containing aluminum tristearate in 480 minutes, the same amount of drug was released from microspheres containing sucrose stearate in only 60 minutes. Chemical structures and concentrations of the dispersing agents were clearly effective on the physical properties of microspheres and their drug-release characteristics.

The effect of the drug/polymer ratio on the properties of the verapamil HCl loaded microspheres.

In this study, the microspheres containing verapamil hydrochloride (VRP) were prepared with Eudragit RS 100 by solvent evaporation method. In the solvent evaporation method one of the parameters which affect to the formation and properties of the microspheres is the variations of drug/polymer ratios. The aim of our study is to examine the effects of this parameter on the VRP loaded microspheres. To achieve this purpose, only drug/polymer ratio was altered while the other formulation parameters were kept constant and percentage yield value, incorporation efficiency, particle size and distribution of the microspheres were analyzed and micrographs of the microspheres were taken to determine the effects of the increase in the polymer amount of formulations. All the dispersed phase viscosities were evaluated by comparing them with the variations in particle size and distribution of the microspheres. In vitro dissolution tests were done by using dissolution media with three different pH in sequence as half-change method with flow through cell and the effect of the variation in polymer ratio on drug dissolution was evaluated according to dissolution test results. As a result of our study, it is thought that the variation in drug/polymer ratios might have an influence on the physical characteristics of the microspheres and the increasing amount of polymer might be result in decreased drug dissolve.