Bioadhesive Nanoparticles as Potent Drug Delivery Carriers.

BACKGROUND: In recent years, numerous scientists have gained interest in nanotechnology- based systems, especially for biomedical applications. Then, nanocarriers present tunable abilities and can be easily functionalized to target specific epithelial cells, tissues, and organs, while various materials can be chosen and generate nanosized particles. At present, nanoparticles that possess bioadhesion have been studied as potent drug carriers since they can easily penetrate and target organs. OBJECTIVE: Aim of this study was to explore the various applications of the bioadhesive nanoparticles found in the literature. METHODS: Authors have studied the literature finding that bioadhesive nanoparticles can be administered via routes such as oral, topical, ocular, dermal, vaginal, etc., according to the clinician's opinion and treatment choice. Therefore, the knowledge of general characteristics of bioadhesive nanoparticles, the bioadhesion theory, and other properties of nanoparticles should be known for developing innovative bioadhesive drug nanocarriers. RESULTS: In this review article, the authors state the current knowledge of theories. In addition, the present categories of nanoparticles and their basic characteristics are also discussed. Finally, the biomedical applications of bioadhesive nanocarriers and the several administration routes are extensively reviewed. CONCLUSION: The review article aims to cover the most current bioadhesive nanoparticles for drug delivery to assist any scientist who desires to study or develop innovative bioadhesive formulations.

IL-1ß, IL-6 and TNF-α expression levels of macrophage cells induced by benzydamine hydrochloride, benzydamine hydrochloride with chitosan, calcium hydroxide and chlorhexidine medicaments: An ELISA study.

The aim of the present study was to evaluate IL-1ß, IL-6 and TNF-α expression levels of macrophage cells induced by benzydamine hydrochloride (BNZ), BNZ with chitosan, calcium hydroxide (CH) and chlorhexidine (CHX) medicaments. Half maximal inhibitory concentrations (IC50) were assessed on THP-1, Saos-2, and CRL-2014 cells using MTT assay. THP-1 cells were differentiated into macrophages with phorbol12-myristate13-acetate and activated with lipopolysaccharide. IL-1ß, IL-6 and TNF-α levels in supernatants were determined using enzyme-linked immunosorbent assay (ELISA). The data were examined with one-way ANOVA and Tukey's multiple comparison test (p=0.05). At the selected concentrations, the cell viability was higher than 50% for chitosan and CH, whereas CHX presented lower IC50 values than BNZ and BNZ+chitosan. According to ELISA results, the lowest IL-1ß, IL-6 and TNF-α values were observed with BNZ+Chitosan 50 µg/mL and BNZ 50 µg/mL. BNZ+chitosan 50 µg/mL combination has revealed promising anti-inflammatory effects. Nevertheless, these findings need to be examined in clinical conditions.

Development of novel mucoadhesive gels containing nanoparticle for buccal administration of dexamethasone

Abstract This study aimed to develop promising and innovative mucoadhesive gel systems containing dexamethasone-loaded nanoparticle to increase the effectiveness of treatment for oral precancerous lesions and to reduce side effects. In this respect, a dexamethasone-loaded nanoparticle formulation was prepared by using emulsification/solvent evaporation method. The nanoparticle has high zeta potential (-10.3±0.5 mV), low particle size (218.42±2.1), low polydispersity index (0.070±0.014) and high encapsulation efficiency (95.018±2.982%). To improve the mucosal retention time, the dexamethasone-loaded nanoparticle was dispersed in mucoadhesive gel using gellan gum. The developed gels offered appropriate pH value, high drug content, suitable mechanical and mucoadhesive performance and appropriate viscosity for mucosal administration. All formulations exhibited plastic flow and typical gel-type mechanical spectra after the determined frequency value. The developed formulations exhibited extended drug release as intended for these systems. Cytotoxicity was tested by MTT assay in human epithelioid carcinoma cell (HeLa) in vitro. The MTT assay showed that the blank formulations were non-toxic to cells. It was observed that the bioactivity of the free dexamethasone was potentiated by mucoadhesive gels containing dexamethasone-loaded nanoparticle in HeLa cells. Results from this study indicate that mucoadhesive gels are effective for the local treatment of precancerous lesions. Our findings showed that the developed formulations were worthy of further studies.

Design and Evaluation of Topical Antioxidant Nanogel Formulations.

Transdermal delivery of an active substance is promising, but a challenging option is available for local and systemic effects. The prolonged residence of formulation in the skin is important for topical delivery. In this study, it was aimed to develop a formulation that can overcome the stability and absorption problems of the vitamin C active substance by preparing nanogels. Nanogel-based materials have high drug loading capacity, biocompatibility, stability, and biodegradability, which are the key points to design a topical drug delivery system. Bovine serum albumin (BSA) and chitosan (CS) were used to prepare nanogels by a simple green self-assembly technique. Prepared nanogels were successfully used to entrap vitamin C, with an entrapment ratio between 86.08% ± 1.29% and 107.93% ± 1.04%. The studies started with vitamin C analysis and continued with characterization studies such as homogeneity, pH, viscosity, rheological properties, zeta potential, polydispersity index, particle size, and in vitro dissolution studies of nanogels. The antioxidant activities of the formulations were also tested by cell culture studies. The antioxidant activities of the nanogels were also tested by in vitro 2,2-diphenyl-1-picrylhydrazyl assay. Although topical vitamin C is effective in many ways, it has a risk of serious stability and absorption problems. The present work was aimed at developing pharmaceutically optimized topical nanogel formulations of vitamin C for antioxidant effect. An optimum nanogel formulation was composed of a 1:4 ratio of CS:BSA with (F19 formulation) in terms of entrapping vitamin C, formulation homogeneity, pH, viscosity, rheological properties, zeta potential, PI, particle size, in vitro dissolution and cell culture studies. The optimized formulation showed higher antioxidant efficacy in vitro than vitamin C. In conclusion, prepared topical nanogel of vitamin C was stable and could be used with promising potential for topical application.

Dexamethasone loaded PLGA nanoparticles for potential local treatment of oral precancerous lesions.

The aim of this study was to develop dexamethasone loaded nanoparticles for the local treatment of oral precancerous lesions. Dexamethasone loaded nanoparticles were prepared using the emulsification/solvent evaporation method. The prepared nanoparticles were characterized for pH, particle size, polydispersity index, zeta potential, morphology, encapsulation efficiency and drug loading. Furthermore, in vitro drug release, stability, ex vivo drug diffusion, and cell culture studies were undertaken. The particle size, polydispersity index, zeta potential, and encapsulation efficiency were found to be approximately 200 nm, 0.2, -10 mV, and 95%, respectively. Atomic Force Microscopy results showed that the formulated nanoparticles had uniform and spherical shape. In vitro release studies demonstrated 80% release of dexamethasone from nanoparticles; the nanoparticles were stable for 6 months. The ex vivo studies revealed no drug diffusion into the receptor media phase which suggests a possible local effect. Cytotoxicity studies showed that nanoparticles were non-cytotoxic against the HK-2 and NIH-3T3 cell lines. Findings of this study suggest that dexamethasone loaded PLGA nanoparticles are promising and can be further investigated as potential treatment of oral precancerous lesions.

Development and in vitro Evaluation of Voriconazole Nanoparticle Formulation for Mucosal Application.

OBJECTIVES: This study aimed to prepare and evaluate mucoadhesive nanoparticle formulations of voriconazole, an antifungal drug, for mucosal application. It was also aimed to develop and validate a HPLC method of voriconazole. MATERIALS AND METHODS: In this study, mucoadhesive nanoparticles containing voriconazole were prepared using a coating polymer of chitosan. The obtained nanoparticles were characterized via particle size, polydispersity index, zeta potential measurement, and mucoadhesion studies. Drug loading capacity was tested for determination of the voriconazole amount in the nanoparticles. In vitro drug release was also examined. The HPLC method was validated for linearity, accuracy, precision (repeatability and reproducibility), specificity, stability, limits of detection (LOD), and limit of quantification (LOQ). RESULTS: In vitro characterization results of the mucoadhesive nanoparticle formulation containing voriconazole was found to be appropriate with a small particle size of 217.1±4.2 nm, a narrow polydispersity index of 0.335±0.042, 99.052±0.424% drug loading, and a positive zeta potential value of +26.82±0.4 mV. Accor-ding to a mucoadhesive study, it can be concluded that the nanoparticle was able to interact with mu-cin due to ionic interaction. Also, the turbidity of nanoparticle/mucin dispersion was higher than the turbidity of mucin dispersion itself. Based on the in vitro drug release, no burst effect was observed, indicating that voriconazole was homogeneously dispersed in the nanoparticle dispersion and that no significant amount of drug was adsorbed onto the nanoparticle surface. The release was found to fol-low a non Fickian diffusion mechanism with first order drug release. The proposed HPLC method was simple, highly sensitive with good linearity, accurate, precise, specific, and stable, showing that the method is useful for routine quality control. CONCLUSION: This study has shown that the mucoadhesive nanoparticle formulation containing voriconazole repor-ted here is a promising candidate for the local treatment of mucosal diseases. The developed HPLC method can be succesfully applied to pharmaceutical preparations containing voriconazole.

Mucoadhesive in situ gel formulation for vaginal delivery of clotrimazole: formulation, preparation, and in vitro/in vivo evaluation.

The purpose of this study was to develop a suitable mucoadhesive in situ gel formulation of clotrimazole (CLO) for the treatment of vaginal candidiasis. For this aim, the mixture of poloxamer (PLX) 407 and 188 were used to prepare in situ gels. Hydroxypropyl methylcellulose (HPMC) K100M or E50 was added to in situ gels in 0.5% ratio to improve the mucoadhesive and mechanical properties of formulations and to prolong the residence time in vaginal cavity. After the preparation of mucoadhesive in situ gels; gelation temperature/time, viscosity, mechanical, mucoadhesive, syringeability, spreadibility and rheological properties, in vitro release behavior, and anticandidal activities were determined. Moreover vaginal retention of mucoadhesive in situ gels was investigated with in vivo distribution studies in rats. Based on the obtained results, it was found that gels prepared with 20% PLX 407, 10% PLX 188 and 0.5% HPMC K100M/E50 might be suitable for vaginal administration of CLO. In addition, the results of in vivo distribution studies showed that gel formulations remained on the vaginal mucosa even 24 h after application. In conclusion, the mucoadhesive in situ gels of CLO would be alternative candidate for treatment of vaginal candidiasis since it has suitable gel properties with good vaginal retention.

Development, characterization, and in vivo assessment of mucoadhesive nanoparticles containing fluconazole for the local treatment of oral candidiasis.

This study aimed to develop a suitable buccal mucoadhesive nanoparticle (NP) formulation containing fluconazole for the local treatment of oral candidiasis. The suitability of the prepared formulations was assessed by means of particle size (PS), polydispersity index, and zeta potential measurements, morphology analysis, mucoadhesion studies, drug entrapment efficiency (EE), in vitro drug release, and stability studies. Based on the optimum NP formulation, ex vivo drug diffusion and in vitro cytotoxicity studies were performed. Besides, evaluation of the antifungal effect of the optimum formulation was evaluated using agar diffusion method, fungicidal activity-related in vitro release study, and time-dependent fungicidal activity. The effect of the optimum NP formulation on the healing of oral candidiasis was investigated in an animal model, which was employed for the first time in this study. The zeta potential, mucoadhesion, and in vitro drug release studies of various NP formulations revealed that chitosan-coated NP formulation containing EUDRAGIT(®) RS 2.5% had superior properties than other formulations. Concerning the stability study of the selected formulation, the formulation was found to be stable for 6 months. During the ex vivo drug diffusion study, no drug was found in receptor phase, and this is an indication of local effect. The in vitro antifungal activity studies showed the in vitro efficacy of the NP against Candida albicans for an extended period. Also, the formulation had no cytotoxic effect at the tested concentration. For the in vivo experiments, infected rabbits were successfully treated with local administration of the optimum NP formulation once a day. This study has shown that the mucoadhesive NP formulation containing fluconazole is a promising candidate with once-a-day application for the local treatment of oral candidiasis.

A new approach to the treatment of recurrent aphthous stomatitis with bioadhesive gels containing cyclosporine A solid lipid nanoparticles: in vivo/in vitro examinations.

AIM: To develop a suitable buccal bioadhesive gel formulation containing cyclosporine A solid lipid nanoparticles (CsA SLNs) for the treatment of recurrent aphthous stomatitis. METHODS: The suitability of the prepared formulations for buccal application was assessed by means of rheological studies, textural profile analysis, and ex vivo drug-release studies. Plastic flows, typical gel-like spectra, and suitable mechanical properties were obtained from prepared formulations. The retention time was explored in in vivo distribution studies and the effect of the gel containing CsA SLNs on the healing of oral mucosal ulceration was investigated in an animal model. In vivo distribution studies are a very important indicator of the retention time of formulations at the application site. RESULTS: Distribution studies showed that 64.76% ± 8.35% of the formulation coded "F8+SLN" remained on the buccal mucosa 6 hours after application. For the second part of the in vivo experiments, 36 rabbits were separated into three groups: the first group was treated with the gel formulation without the active agent; the second group with the gel formulation containing CsA SLNs; and the third group, used as the control group, received no treatment. Wound healing was established by scoring of the rate of wound healing on Days 3, 6, 9, and 12. Histological observations were made on the same days as the scoring studies. The bioadhesive gel formulation that included CsA SLNs increased the rate of mucosal repair significantly. CONCLUSION: This study has shown that the bioadhesive gel formulation containing CsA SLNs reported here is a promising candidate for the topical treatment of recurrent aphthous stomatitis.