Preparation and In Vitro Characterization of Enoxaparin Nano-liposomes through Different Methods.

Purpose: Enoxaparin has been widely used as a choice drug for treatment and prevention of different coagulation disorders. Orally administered enoxaparin encounters with gastrointestinal barrier because of its high water solubility, high molecular weight and significant negative charge. Since, the nano-liposomes has gained great interest for oral drug delivery, we decided to introduce the best protocol for preparing enoxaparin nano-liposomes through in vitro characterization. Methods: Nano-liposomes were prepared by ethanol injection, thin film hydration, and double emulsion/solvent evaporation methods. Size distribution, zeta potential, loading efficiencies, and in vitro drug release of nano-liposomes were also studied. Results: The mean vesicle size was obtained under 100 nm, and the zeta potential was highly negative through all preparation methods. Nano-liposomes prepared by double emulsion/ solvent evaporation (DE) technique could entrap more of this hydrophilic drug (43 ± 7.1 %), but through thin layer hydration (TL) and ethanol injection (EI) only 28.4± 3.2% and 17.3 ± 2.5% of drug could be loaded into synthesized carriers. Drug release from these carriers was also obtained 42.17±1.72%, 29.43±0.34% and 32.27±0.14%, in 24 hours for EI, TL, and DE methods, respectively. Conclusion: Here, we can introduce double emulsion/solvent evaporation method as an acceptable method for enoxaparin loading, although some toxicity and in-vivo tests are also necessary to fully understand the potential of this formulation.

Preparation and characterization of cyclodextrin nanosponges for bortezomib delivery.

BACKGROUND: Bortezomib (BTZ) as an anticancer drug has been used through the injection pathway. RESEARCH DESIGN AND METHODS: Two types of Cyclodextrin nanosponges (CDNSs) were synthesized and studied by DLS, TEM, FTIR, and DSC instruments for BTZ delivery. Both carriers were analyzed for loading efficiencies and in-vitro release. Cell studies and intestinal permeability of selected CDNS were determined using MTT and SPIP method, respectively. RESULTS: Both types of CDNSs, encapsulated BTZ in their nano-porous structure, but better loading was shown in CDNS 1:4. FTIR and DSC results proved considerable encapsulation of BTZ into CDNSs. The slow and prolonged release profile was observed for CDNS 1:4 in comparison with CDNS 1:2. Based on in-vitro results, BTZ-CDNS 1:4 was chosen as a selected nanosystem for further analysis. This nontoxic carrier revealed considerable uptake (93.9% in 3 h) against the MCF-7 cell line but indicated higher IC50 in comparison with the plain drug. This carrier also could improve the rat intestinal permeability of BTZ almost 5.8 times. CONCLUSION: CDNS 1:4 has the ability to be introduced as a nontoxic carrier for BTZ delivery with its high loading, controlled release manner, high cellular uptake, and permeability improvement characteristics.

Axial pharmaceutical properties of liposome in cancer therapy: Recent advances and perspectives.

Evaluation of axial properties including preparation, surface functionalization, and pharmacokinetics for delivery of pharmacologically active molecules and genes lead to pharmaceutical development of liposome in cancer therapy. Here, analysis of effects of the axial properties of liposome based on cancer treatment modalities as individually and coherently is vital and shows deserving further investigation for the future. In this review, recent progress in the analysis of preparation approaches, optimizing pharmacokinetic parameters, functionalization and targeting improvement and modulation of biological factors and components resulting in a better function of liposome in cancer for drug/gene delivery and immunotherapy are discussed. Here, recent developments on liposome with vaccines and immunoadjuvant carriers, and antigen-carrier system to cancer immunotherapy are introduced.

Cyclodextrin-based nanosponges as promising carriers for active agents.

INTRODUCTION: In recent years, new drug delivery systems have attempted to overcome the undesirable pharmacokinetic problems of various drugs. Among them, cyclodextrin nanosponges (CDNSs) attract great attention from researchers for solving major bioavailability problems such as inadequate solubility, poor dissolution rate, and the limited stability of some agents, as well as increasing their effectiveness and decreasing unwanted side effects. This novel system can also be prepared as different dosage forms. AREAS COVERED: This review will give an insight into the effects of CDNSs on the pharmacokinetic parameters and permeability of active agents. Different classes of drugs delivered by this system are mentioned and we designate which CD is used most widely in their production process. We also inform why this carrier can be introduced as a versatile carrying system in pharmaceutical fields. Registered patents about this novel system in various fields are also mentioned. EXPERT OPINION: The readers will be informed on CDNSs as a novel carrier especially for the delivery of drugs. Versatile characteristics and applications of them can also be known by this review. Finally, CDNSs may be introduced as a remarkable vehicle in the pharmaceutical market in coming years.

Methanolic Extract of Ficus carica Linn. Leaves Exerts Antiangiogenesis Effects Based on the Rat Air Pouch Model of Inflammation.

The antiangiogenesis effect of Ficus carica leaves extract in an air pouch model of inflammation was investigated in rat. Inflammation was induced by injection of carrageenan into pouches. After antioxidant capacity and total phenolic content (TPC) investigations, the extract was administered at 5, 25, and 50 mg/pouch, and then the volume of exudates, the cell number, TNFα, PGE2, and VEGF levels were measured. Angiogenesis of granulation tissues was determined by measuring hemoglobin content. Based on the DPPH assay, the extract had significant antioxidant activity with TPC of 11.70 mg GAE/100 g dry sample. In addition, leukocyte accumulation and volume of exudate were significantly inhibited by the extract. Moreover, it significantly decreased the production of TNFα, PGE2, and VEGF, while angiogenesis was significantly inhibited by all administered doses. Interestingly, attenuation of angiogenesis and inflammatory parameters (except leukocyte accumulation) by the extract was similar to that shown by diclofenac. The extract has anti-inflammatory effects and ameliorated cell influx and exudation to the site of the inflammatory response which may be related to the local inhibition of TNFα, PGE2, and VEGF levels as similarly shown by diclofenac. The antiangiogenesis and anti-VEGF effects of Ficus carica may be correlated with its significant antioxidant potentials.

Evaluation of general toxicity, anti-oxidant activity and effects of ficus carica leaves extract on ischemia/reperfusion injuries in isolated heart of rat.

PURPOSE: This study was aimed to evaluate general toxicity, anti-oxidant activity and effects of Ficus carica leaves extract on ischemia/reperfusion injuries. METHODS: Antioxidant activity, total phenolic and flavonoid compounds of 70% methanolic extract of Ficus carica leaves were measured. The general toxicity test was carried out by brine shrimp lethality assay. Isolated hearts of male rats were mounted on a Langendorff apparatus and perfused with modified Krebs-Henseleit solution. In control group, the hearts were perfused with normal Krebs solution, however, treatment groups received enriched solution with the extract (0.04, 0.2 and 1 mg/ml) during stabilization and reperfusion (after 30 min global ischemia), respectively. Cardiac arrhythmias were analyzed and TTC method was used for infarct size determination. RESULTS: The extract displayed antioxidant activity in the DPPH assay (RC50=0.06666 mg/ml). Total phenolic content was 12.29 mg GAE/100 g dry sample and the amount of flavonoids was calculated 40.729 mg/g. LD50 value by brine shrimp test was 0.158 mg/ml. The extract decreased number of VEBs, incidence and duration of Rev VF with clear reduction in infarct size and infarct volume (P<0.001). CONCLUSION: Ficus carica decreased ischemia/reperfusion-induced injuries. These protections are probably due to antioxidant capacity and the existence of flavonoid and phenolic compounds in the extract.