ABSTRACT
Objective: This study aimed to evaluate a co-encapsulated pegylated nano-liposome system based on two herbal anti-tumor drugs, silibinin and glycyrrhizic acid, for delivery to a hepatocellular carcinoma [HCC] cell line [HepG2]
Materials and Methods: In this experimental study, co-encapsulated nano-liposomes by the thin layer film hydration method with HEPES buffer and sonication at 60% amplitude. Liposomes that co-encapsulated silibinin and glycyrrhizic acid were prepared with a specified molar ratio of dipalmitoylphosphatidylcholine [DPPC], cholesterol [CHOL], and methoxy-polyethylene glycol 2000 [PEG2000]-derived distearoyl phosphatidylethanolamine [mPEG2000-DSPE]. We used the MTT technique to assess cytotoxicity for various concentrations of co-encapsulated nano-liposomes, free silibinin [25% w/v] and glycyrrhizic acid [75% w/v] on HepG2 and fibroblast cell lines over a 48-hour period
Results: Formulation of pegylated nano-liposomes showed a narrow size distribution with an average diameter of 46.3 nm. The encapsulation efficiency [EE] for silibinin was 24.37%, whereas for glycyrrhizic acid it was 68.78%. Results of in vitro cytotoxicity showed significantly greater co-encapsulated nano-liposomes on the HepG2 cell line compared to the fibroblast cell line. The half maximal inhibitory concentration [IC50] for co-encapsulated pegylated nanoliposomal herbal drugs was 48.68 microg/ml and free silibinin with glycyrrhizic acid was 485.45 microg/ml on the HepG2 cell line
Conclusion: This in vitro study showed that nano-liposome encapsulation of silibinin with glycyrrhizic acid increased the biological activity of free drugs, increased the stability of silibinin, and synergized the therapeutic effect of silibinin with glycyrrhizic acid. The IC50 of the co-encapsulated nano-liposomes was lower than the combination of free silibinin and glycyrrhizic acid on the HepG2 cell line
ABSTRACT
Silver nanoparticles [Ag NPs] have been widely used as new potent antimicrobial agents in cosmetic and hygienic products. Present study compares the tissue levels of Ag NPs in different organs of Guinea Pigs quantitatively after dermal application and analysis the morphological changes and pathological abnormalities on the basis of the Ag NPs tissue levels. Before toxicological assessments, the size of colloidal nanosilver was recorded by X-Ray Diffraction and Transmission Electron Microscope tests and the sizes of samples were recorded in sizes less than 100 nm. For toxicological evaluation, male guinea pigs were exposed to three concentrations of Ag NPs [100, 1000 and 10000 ppm] according to acute pretests for further assessments in subchronic model in a period of 13 weeks. A close correlation between dermal exposure and tissue levels of Ag NPs was found [p < 0.05] and tissue uptakes happened in dose dependent manner with the following ranking: kidney>muscle>bone>skin>liver>heart >spleen. In histopathological studies, severe proximal convoluted tubule degeneration and distal convoluted tubule were seen in the kidneys of the middle and high-dose animals. Separated lines and marrow space narrow were determined as two major signs of bone toxicities which observed in three different dose levels of Ag NPs. Increased dermal dose of Ag NPs caused cardiocyte deformity, congestion and inflammation. The three different Ag NPs concentration gave comparable results for several endpoints measured in heart, bone and kidney, but differed in tissue concentrations and the extent of histopathological changes. It seems that Ag ions could be detected in different organs after dermal exposure, which has the potential to provide target organ toxicities in a time and dose dependent manner
Subject(s)
Animals , Male , Nanostructures/toxicity , Skin/drug effects , Guinea Pigs , Dose-Response Relationship, Drug , Microscopy, Electron, Transmission , Toxicity Tests, AcuteABSTRACT
Antibiotic resistance to microorganisms is one of the major problems faced in the field of wound care in burns patients. Silver nanoparticles have come up as potent antimicrobial agent and are being evaluated in diverse medical applications ranging from silver based dressings to silver coated medical devices. We aimed in present study to test the release of nanosilver from nanosilver wound dressing and compare the dermal and systemic toxicity of nanosilver dressings in a repeated dose [21 days] model. Under general anesthesia, a limited standard 2nd degree burns were provided on the back of each rat in all treatment, negative control [simple dressing] and 5% silver nitrate groups, each contained 5 male wistar rats. According to the analysis made by atomic absorption spectrometry, the wound dressings released 0.599 +/- 0.083 ppm of nanosilver during first 24 hrs of study. Daily observations were recoded and wounds were covered with new dressings each 24 hrs. Burn healing was observed in nanosilver wound dressing group in shorter time periods than the control groups. In toxicity assessment, this dressing didn't cause any hematological and histopathological abnormalities in treatment group but biochemical studies showed significant rise of plasma transaminase [ALT] at the endpoint [21 days] of the study [P=0.027]. Portal mononuclear lymphoid and polymorphonuclear leukocyte infiltrations in three to four adjacent foci were recognized around the central hepatic vein in treatment group. Mild hepatotoxic effects of nanosilver wound dressing in wistar rat emphasize the necessity of more studies on toxicity potentials of low dose nanosilver by dermal applications