Fatal Candida albicans infections in the mucosal system can occur in association with immune-compromised diseases and dysbacteriosis. Currently, amphotericin B (AmB) is considered to be the most effective antibiotic in the treatment of C. albicans infections, but its clinical application is limited by side effects and poor bioavailability. In order to use AmB in the local treatment of oral C. albicans infections, AmB/MPEG-PCL-g-PEI (monomethoxy poly(ethylene glycol)-poly(epsilon-caprolactone)-graft-polyethylenimine, MPP) micelles were prepared. A series of characterizations were performed. The micelles allowed a sustained in vitro release in both normal oral conditions (pH 6.8) and C. albicans infection conditions (pH 5.8). Then, buccal tablets containing freeze-dried powder of AmB/MPP micelles were produced by direct compression process and evaluated as regards to weight variation, hardness, and friability. In vitro drug release of the buccal tablets was measured in both the United States Pharmacopeia dissolution apparatus and the dissolution rate test apparatus, which was previously designed for simulating in vivo conditions of the oral cavity. The buccal tablets could sustainably release within 8 h and meet the antifungal requirements. Regarding safety assessment of AmB/MPP micelles, in vivo histopathological data showed no irritation toward buccal mucosa of the rats in both optical microscopy and ultrastructure observation of the tissues. MTT experiment proved that AmB/MPP micelles reduced the cytotoxicity of AmB. The micelles delivered through the gastrointestinal route were also found to be non-systemic toxicity by liquid chromatography-mass spectrometry analysis. Furthermore, the antifungal action of AmB/MPP micelles was evaluated. Although AmB/MPP had no obvious improvement as compared to AmB alone in the antifungal effect on planktonic C. albicans, the micelles significantly enhanced the antifungal activity against the biofilm state of C. albicans. Thus, it was concluded that AmB/MPP micelles represent a promising novel drug delivery system for the local treatment of oral C. albicans infections.

Naringenin-loaded monomethoxy poly(ethylene glycol)-poly (ε-caprolactone) (MPEG-PCL) nanoparticles (NARNP) and their formulation into buccal tablets using mucoadhesive polymers were developed to improve the solubility of naringenin and to treat oral inflammatory and ulcerative diseases. In our work, physicochemical characterizations of NARNP including particle size, zeta potential, transmission electron microscopy (TEM), differential scanning calorimetery, Fourier transform infrared spectroscopy and in vitro release were studied. NARNP buccal tablets and control buccal tablets containing MPEG-PCL copolymers and mannitol respectively were prepared and they were evaluated by weight variation, hardness, friability and in vitro release. NARNP had a small size (<100 nm), good encapsulation efficiency (95.26 ± 1.15%), and high drug loading (9.95 ± 0.15%). The lyophilized powder of NARNP showed good stability and re-solubility. For the in vitro release study of buccal tablets, Drug dissolution rate was investigated by the USP I method. To simulate in vivo conditions of the oral cavity, a new dissolution test apparatus was designed for assessment of drug release. Compared to control groups, buccal tablets containing NARNP showed more rapid and complete drug release (more than 80%) over 12 h using two dissolution test apparatuses. NARNP incorporated into buccal tablets effectively improved the release of naringenin. With desirable drug release and release time (12 h), NARNP buccal tablets may be an efficient vehicle for treatment of oral inflammatory and ulcerative diseases.

Corneal neovascularization (CNV) is one of the most important causes of visual impairment worldwide. Dasatinib, a poorly water-soluble tyrosine kinase inhibitor with dual Src family kinase and platelet derived growth factor receptor inhibiting capability, has great potential in the treatment of CNV. In this study, dasatinib was successfully encapsulated into a nanostructured lipid carrier (Dasa-NLC) and the size was approximately 78 nm with a small polydispersity index. The NLC increased the solubility of dasatinib by more than 1220 times, sustained the drug release, reduced the ocular toxicity and facilitated its penetration into the cornea. Dasa-NLC significantly inhibited the proliferation, migration and tube formation of HUVEC cells, the three most important angiogenesis-related cellular changes of the CNV. Next, the in vivo anti-CNV effect of Dasa-NLC was evaluated using an alkaline burned mice CNV model, in which the development of the CNV and pathological changes of the cornea were significantly inhibited. The immunohistochemistry analysis indicated that Dasa-NLC could inhibit both the expression and activation of Src family kinase, a key component in the angiogenesis cascade. Therefore, Dasa-NLC showed considerable promise in the treatment of CNV.