Silver Nanocolloids Loaded with Betulinic Acid with Enhanced Antitumor Potential: Physicochemical Characterization and In Vitro Evaluation.

Betulinic acid (BA), a natural compound with various health benefits including selective antitumor activity, has a limited applicability in vivo due to its poor water solubility and bioavailability. Thus, this study focused on obtaining a BA nano-sized formulation with improved solubility and enhanced antitumor activity using silver nanocolloids (SilCo and PEG_SilCo) as drug carriers. The synthesis was performed using a chemical method and the physicochemical characterization was achieved applying UV-Vis absorption, transmission electron microscopy (TEM), Raman and photon correlation spectroscopy (PCS). The biological evaluation was conducted on two in vitro experimental models-hepatocellular carcinoma (HepG2) and lung cancer (A549) cell lines. The physicochemical characterization showed the following results: an average hydrodynamic diameter of 32 nm for SilCo_BA and 71 nm for PEG_SilCo_BA, a spherical shape, and a loading capacity of 54.1% for SilCo_BA and 61.9% for PEG_SilCo_BA, respectively. The in vitro assessment revealed a cell type- and time-dependent cytotoxic effect characterized by a decrease in cell viability as follows: (i) SilCo_BA (66.44%) < PEG_SilCo_BA (72.05%) < BA_DMSO (75.30%) in HepG2 cells, and (ii) SilCo_BA (75.28%) < PEG_SilCo_BA (86.80%) < BA_DMSO (87.99%) in A549 cells. The novel silver nanocolloids loaded with BA induced an augmented anticancer effect as compared to BA alone.

Bisphosphonates-induced osteonecrosis of the jaw - epidemiological, clinical and histopathological aspects.

INTRODUCTION: Osteonecrosis of the jaw (ONJ) is a multifactorial condition associated with bisphosphonates (BPs) treatment, head and neck irradiation, malignancy, chemotherapy, periodontal disease or trauma. The first cases of BPs-related ONJ (BRONJ) were reported over a decade ago. PATIENTS, MATERIALS AND METHODS: The study was retrospective and analyzed archived material. The study included 38 patients diagnosed and treated in the Clinic of Oral and Maxillofacial Surgery, Emergency City Hospital, Timisoara, Romania, for BRONJ, between 2013 and 2016. For all the cases were noted gender, age, localization of osteonecrosis, therapeutic indications for BPs (osteoporosis or malignancy), history of radiotherapy or chemotherapy, presence of bone metastases. If the treatment consisted in surgical removal of necrotic bone, the surgically removed specimens were sent to Service of Pathology of the same Hospital. The excised specimens were prepared with routine histological technique. RESULTS: All the patients included in the current study were diagnosed with BRONJ. The patient history and clinical characteristics were the most useful diagnostic methods. Radiographic changes are not significant in early stages of osteonecrosis. The prevalence of BPs-associated ONJ is higher between 55-74 years old. CONCLUSIONS: ONJ is an important complication of BPs medication. The majority of affected patients develop this complication after dentoalveorar surgery, especially after dental extraction. Therefore, a good state of dental health is one of the most important directives when dealing with potential candidates for BPs therapy.