RGD peptide grafted polybutylene adipate-co-terephthalate/gelatin electrospun nanofibers loaded with a matrix metalloproteinase inhibitor drug for alleviating of wounds: an in vitro/in vivo study.

The objective of the present study was the fabrication of a wound dressing membrane based on RGD modified polybutylene adipate-co-terephthalate (PBAT)/gelatin nanofibrous structures loaded with doxycycline (DOX). This type of nanofiber for wound healing has not been reported so far and is quite novel. PBAT and gelatin nanofibers were separately electrospun using double needles electrospinning setup. Electrospinning variables were optimized to obtain bead-free thin nanofibers. The amount of drug loaded and release were measured in different concentrations of DOX and PBAT. MMPs inhibition was studied by polyacrylamide gel-zymography. Then, surface of the nanofibers was modified with RGD peptide, and their antimicrobial effect was investigated on Staphylococcus aureus and Pseudomonas aeruginosa. Effect of developed nanofibrous membranes on L929 fibroblast cells proliferation, adhesion and closure of excised wounds in rat were also studied. PBAT/gelatin nanofibrous structures with average fiber diameter of 75-529 nm were developed successfully. Drug release study revealed that about 65% of DOX was released from the optimized formulation (P17D1.6) after 20 h. The developed DOX loaded membrane inhibited the MMPs activity and showed no cytotoxicity. RGD surface-modified PBAT/gelatin nanofibers significantly improved the wound closure and histopathological results (re-epithelialization, collagen deposition, and angiogenesis) in rats compared to the control groups. Overall, RGD immobilized PBAT/gelatin nanofibrous membrane may have a potential application for wound healing.

Poly (butylene adipate-co-butylene terephthalate) nanoparticles prepared by electrospraying technique for docetaxel delivery in ovarian cancer induced mice.

OBJECTIVE: Ovarian cancer is still a major cause of morbidity and mortality. Docetaxel (DTX) is one of the most notable cytotoxic agents for treatment of ovarian cancer. However, its side effects proposed considerable problems to the patients. SIGNIFICANCE: Polymeric nanoparticles (NPs) of poly (butylene adipate-co-butylene terephthalate) (Ecoflex®), a biodegradable and biocompatible polymer, were prepared for the first time by the upgradeable electrospraying technique. METHODS: The formulation and procedure variables were optimized using Design Expert software, and effect of each variable on particle size, particle size distribution, drug entrapment efficiency, and drug release of the NPs were evaluated. Then, in vitro cytotoxicity, cellular uptake, X-ray diffraction pattern, and morphological characteristics of the optimized NPs were evaluated. Finally, in vivo efficacy of the DTX-loaded NPs was evaluated on tumor bearing nude mice. RESULTS: The optimum condition for production of NPs included voltage of 20 kV, 12 cm distance between electrodes, feeding rate of 1 mL/hr, polymer to drug ratio of 3:1, 1 w/v% of Pluronic-F127 and dichloromethane to dimethyl formamide ratio of 2.7:1. Fluorescent microscopy test showed the NPs were successfully up-taken by ovarian cancer cells. In vitro cytotoxicity test confirmed no cytotoxic effect caused by blank NPs, while cell viability of the DTX loaded NPs was significantly lower than the free DTX (p < .05). The NPs significantly enhanced anti-tumor efficacy of the drug in nude mice (p < .05). CONCLUSION: The Ecoflex® NPs could potentially provide a suitable alternative for currently available formulations of DTX.

Enhancement of solubility and antidiabetic effects of Repaglinide using spray drying technique in STZ-induced diabetic rats.

The purpose of the study was to enhance the solubility of the poorly water-soluble drug, Repaglinide using spray drying based solid dispersion technique by different carriers including Eudragit E100, hydroxyl propyl cellulose Mw 80 000 and poly vinyl pyrollidone K30. Optimization of the best formulation was carried out according to drug solubility, release profile, particle size and angle of repose of the solid dispersions. The optimized sample was characterized using X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The morphology of the dispersions was studied by SEM. The blood glucose lowering effect of spray dried solid dispersions was studied in normal and streptozocin-induced diabetic rats. The results showed that Eudragit E100 in 1:3 ratio could enhance drug solubility by 100-fold. DSC studies indicated a marked change in melting point of the drug possibly due to strong hydrogen bonds between the drug and Eudragit, while FT-IR study did not show obvious interactions between them. According to XRPD results Repaglinide converted to an amorphous state in the spray dried dispersions. Spray dried Repaglinide reduced the blood glucose level significantly during the 8 h of obtaining blood samples in comparison with untreated drug (p < 0.05).

Optimization and comparison of unidirectional lidocaine-loaded buccal patch with the articaine-loaded buccal patch to reduce injection pain and increment of patients' compliance in dental procedures: A double-blind randomized controlled trial.

Introduction: Nervous patients often postpone dental visits until they are in severe pain, exacerbating anxiety. Buccal patches provide a noninvasive method of delivering drugs between the upper gum and cheek, offering local and systemic effects. Prior research has demonstrated the effectiveness, safety, and reliability of topical lidocaine or articaine patches for oral anesthesia. Consequently, this study aimed to develop a three-layered buccal drug delivery system for topical anesthetics. Methods: The first step was preparing and optimizing lidocaine-loaded three-layer patches using Design-expert software. The effects of ethylcellulose, Eudragit, and carbopol concentrations were investigated on patch characteristics, including mucoadhesion, Young's modulus, and Elongation-at-break. Subsequently, patches were fabricated according to the optimized formulation determined by the software, and their efficacy was studied in a randomized, double-blind clinical trial. Participants received either lidocaine or articaine-loaded compared with placebo in a split-mouth study. They evaluated their pain levels using the Visual Analogue Scale (VAS), and the onset and duration of action were recorded for each treatment. Results: According to the results, increasing ethyl cellulose and Eudragit concentrations improved mucoadhesion force (p < 0.05) while increasing ethyl cellulose and reducing Eudragit concentrations increased Young's modulus (p < 0.05). Increasing Carbopol and decreasing Eudragit concentrations also raised elongation at break significantly in the patch (p < 0.05). Treatment with lidocaine-loaded patches resulted in lower VAS scores and faster onset of action in patients than articaine-loaded patches. However, the duration of the effect was longer in the former(p < 0.001). Conclusion: Based on the responses' analysis, the formulation of the 3-layered buccal patch was optimized. This formulation comprised 4.72 % ethyl cellulose, 2 % Carbopol, and 5 % eudragit. Clinical evaluation results showed that loading the optimized formulation with lidocaine was more efficient in controlling the injection pain than articaine. Trial registration: This trial was prospectively registered with irct.behdasht.gov.ir (registration number: IRCT20210118050067N2) on Aug 19, 2022.

Design and preparation of an electromechanical implant prototype for an on-demand drug delivery.

INTRODUCTION: A bio-implant is a drug-delivery system that is implanted in the human body for a period of more than 30 days. Electromechanical systems are one type of bio-implant that has recently been introduced as a new generation of targeted drug delivery methods. The overarching goal of utilizing these systems is to integrate electrical and mechanical features in order to benefit from the numerous applications of these two systems when used together. The current study aimed to design a prototype of an electromechanical system using Fused Deposition Modeling (FDM), Selective Laser Sintering (SLS), and MultiJet Fusion (MJF) techniques for drug delivery that can release a specific drug dosage in the patient's body by connecting to a sensor or under the control of a signal sent by the physician. METHODS: Initially, the implant chambers were created in the form of a hollow cylinder, closed at one end, using three different types of 3D printers: FDM, SLS, and MJF. Each implant was then filled with a model drug (pentoxifylline) and sealed with a thin gold membrane. To achieve the lowest voltage required to melt the gold membrane, an electric circuit with controllable DC voltage generator was designed. Finally, the mechanical resistance, drug release rate, and surface morphology of the designed implants were evaluated. RESULTS: The MJF 3D printer, overally, had higher printing precision and repeatability than other printers; however, the implants printed by the FDM 3D printer were more accurate than other techniques (P value < 0.001), similar to the dimensions of the designed file. The mechanical resistance of the implants was also evaluated, and the polylactic acid implants printed by FDM had the highest value of Young's modulus in both the standard samples and the designed implants. During the 3-month drug leakage study, FDM 3D printed implant had a greater ability to store the desired drug load (P value < 0.001), Furthermore, the SEM micrographs revealed that the polylactic acid implants printed by FDM had minimal porosity in their structure and the layers were well adhered together. The gold membrane with a middle diameter of 2 mm required the lowest voltage of 6 V. As a result, the final electrical circuit was designed with smaller dimensions in order to achieve the voltage required to melt the gold membrane. CONCLUSION: Due to the lack of drug leakage and other mechanical studies, the electromechanical implant produced by the FDM 3D printer was chosen as the optimal electromechanical implant in this study. Along with the designed small circuit, this implant can release a drug dosage in the patient's body at the physician's demand.

Magnetophoretic Intranasal Drug-loaded Magnetic Nano-aggregates as a Platform for Drug Delivery in Status Epilepticus.

BACKGROUND: Status epilepticus is associated with substantial morbidity and neuronal necrosis, and the duration of the seizure would affect its following complications. Eliminating the duration would have valuable outcomes; however, the presence of BBB is an obstacle. The purpose of the current study was to achieve a nose-to-brain magnetic drug delivery system to accelerate the onset of action, and to reduce the mucociliary clearance via implementing the magnetic field. MATERIALS AND METHODS: The drug-entrapped magnetic nanoaggregates were prepared via a 2-step method, synthesis of the magnetic nanoparticles and drug loading. Optimization of the variables, including ammonium hydroxide:water ratio, beta-cyclodextrin%, duration of the mixing time, amount of Pluronic, and drug:magnetic nanoaggregates mass ratio was performed according to particle size, PDI, zeta potential, release profile and entrapment efficiency. The efficacy of optimized formulation was assessed in the animal model. RESULTS: According to the analysis performed by the software, drug-to-nanoparticle ratio and the duration of mixing time were found to be significantly effective (p < 0.05) for entrapment efficiency and particle size distribution, respectively. The optimum formulation with an approximate average size of 581 nm and 61% entrapment efficiency was obtained, which released about 80% of its drug content within the first 20 minutes. The in vivo efficacy was significantly improved (p < 0.05) by administration of magnetic nanoaggregates in the presence of a simple external magnet placed on the glabellar region of the animals, compared to the control groups. CONCLUSION: This drug delivery system could be suggested as a fast-acting alternative for seizure cessation in status epilepticus emergencies.

The Effectiveness of Perovskia abrotanoides Extract Topical Formulation on the Cutaneous Leishmaniasis: A Randomized Controlled Clinical Trial.

Objective: Despite many attempts to treat leishmaniasis, new approaches are necessary to reduce the burden of disease. Perovskia abrotanoides (Brazambel) has shown significant effects against Leishmania parasites in some studies. This study aimed to investigate the effects of P. abrotanoides extract topical formulation on cutaneous leishmaniasis. Methods: In this randomized controlled clinical trial, patients with cutaneous leishmaniasis were assigned to experimental (n = 18) and control (n = 18) groups. Both groups received intralesional meglumine antimoniate (Glucantime®). The experimental group also received 5% Brazambel extract ointment once a day. The interventions continued until the complete healing of the lesions (reepithelialization) for a maximum of 8 weeks. The clinical response, defined as complete response (reepithelialization >75%), partial response (reepithelialization 50%-75%), or treatment failure (reepithelialization <50%), was compared between the groups. Findings: The percentage of reepithelialization in the experimental group (4th week: 64.44 ± 25.13; 8th week: 83.85 ± 11.54) was higher than the control group (4th week: 53.97 ± 25.88; 8th week: 76.27 ± 21.67); however, the differences were not statistically significant (P = 0.252 and 0.494, respectively). Moreover, there was no significant difference between the experimental and control groups regarding the rate of complete healing (88.9% vs. 72.2%, respectively). Conclusion: The use of P. abrotanoides extract 5% topical formulation does not affect the healing of cutaneous leishmaniasis.

Fabrication and optimization of electrospun polymeric nanofibers loaded with 5-fluorouracil and rosemary extract.

BACKGROUND: Topical 5-fluorouracil [5FU] is one of the mostly prescribed medications for different types of skin cancer; however, it is associated with drug resistance and adverse effects. Rosemary extract has promising dose-dependent antitumor effects, as well as a synergistic effect in combination with 5-fluorouracil besides sensitizing the 5-FU-resistant cells. OBJECTIVE: Polymeric nanofibers loaded with 5FU and rosemary extract were optimized to combine both ingredients in one controlled release drug delivery system, aiming to enhance the efficacy while retaining the adverse effects. METHOD: Polymeric nanofibers loaded with 5-FU and rosemary were fabricated via electrospinning technique. Design expert software was utilized to study the effect of independent variables including polymer concentration, voltage, and feeding rate on the characteristics of the resulting nanofibers. Afterwards, the FTIR spectrum and release kinetic of the drug and extract from the optimized nanofibers and their cytotoxic effect against A375 cell line were investigated. RESULTS: The formulation composed of 6.65% PVA electrospun at 1 mL.h-1 and 17.5kV was chosen as the optimum fabrication condition. The mean diameter of the optimized nanofibers was 755 nm. The drug and rosemary extract contents were 75.38 and 93.42%, respectively. The fabrication yield was 100%, bioadhesion force was 1.28 N, and bead abundance was 10 per field. The cytotoxicity of the optimized formulation was significantly higher than the control groups. CONCLUSION: According to the appropriate loading percent, release efficiency and release kinetics, bioadhesion force, and cytotoxicity, these nanofibers could be further investigated as a topical treatment option to increase the efficacy of 5-FU.

HER-2 aptamer-targeted Ecoflex® nanoparticles loaded with docetaxel promote breast cancer cells apoptosis and anti-metastatic effect.

Breast cancer is a major cause of cancer mortality. Regarding the advantages of polymeric nanoparticles as drug delivery systems with targeting potential, in this study the antitumor mechanism of targeted docetaxel polymeric nanoparticles of Ecoflex® was exploited. Since the overexpression of HER-2 receptor in breast cancer cases is associated with poor prognosis and more aggressive disease, the proposed nanoparticles were conjugated to HER-2 specific aptamer molecules. In vitro cytotoxicity was evaluated by MTT assay. Flow-cytometry analysis was performed to evaluate the cellular uptake of nanoparticles loaded with a fluorescent probe. Anti-migration effects of samples were studied. Annexin IV-FITC and propidium iodide were implemented to investigate apoptosis induction and cell cycle analysis. Enhanced cytotoxicity compared with free docetaxel was explained considering improved cellular uptake of the nanoparticles and induced apoptosis in a larger portion of cells. Lower relative migration demonstrated enhanced anti-migration effect of nanoparticles, and cell cycle was arrested in G2/M phase using both formulations so the anti-microtubule mechanism of the drug was not altered. Therefore, this system could offer a potential substitute for the currently marketed docetaxel formulations, which may reduce adverse effects of the drug, while further in vivo and clinical investigations are required.

Biodistribution, Safety and Organ Toxicity of Docetaxel-Loaded in HER-2 Aptamer Conjugated Ecoflex® Nanoparticles in a Mouse Xenograft Model of Ovarian Cancer.

BACKGROUND: Docetaxel is a notably efficient anticancer drug administered for several types of malignancies including ovarian cancer. However, various side effects caused either by the nonspecific distribution of the active ingredient or by high contents of Tween 80 and ethanol in the currently marketed formulations, could even deprive the patients of the treatment. OBJECTIVES: In the current study, a novel targeted delivery system composed of Ecoflex® polymeric nanoparticles loaded with docetaxel and equipped with HER-2 specific aptamer molecules was evaluated regarding blood and tissue toxicity, and biodistribution. METHOD: The tumor-bearing nude mice, achieved by subcutaneous injection of SKOV-3 cells, were divided into four groups treated with normal saline, Taxotere®, targeted docetaxel nanoparticles, and non-targeted docetaxel nanoparticles. Few patents were alos cied in the article. RESULTS: According to the results of hematologic evaluations, almost all hematologic parameters were in normal range with no significant difference among the four groups. Histopathological studies revealed that treatment with targeted nanoparticles caused a remarkable reduction in mitosis in tumor sections and overall reduced organ toxicity compared with Taxotere®. The only exception was spleen in which more damage was caused by the nanoparticles. The results of the biodistribution study were also in accordance with pathological assessments, with significantly lower drug concentration in non-tumor tissues, except for spleen, when targeted nanoparticles were used compared with Taxotere®. CONCLUSION: These results could evidence the efficiency of the targeted delivery system in concentrating the drug cargo mostly in its site of action leading to the elimination of its adverse effects caused by exposure of other tissues to the cytotoxic agent.

Trastuzumab-conjugated nanoparticles composed of poly(butylene adipate-co-butylene terephthalate) prepared by electrospraying technique for targeted delivery of docetaxel.

Human epidermal growth factor receptor 2 (HER-2) is overexpressed in 20-30% of human breast cancers, associated with poor prognosis and tumour aggression. The aim of this study was the production of trastuzumab-targeted Ecoflex nanoparticles (NPs) loaded with docetaxel and in vitro evaluation of their cytotoxicity and cellular uptake. The NPs were manufactured by electrospraying and characterised regarding size, zeta potential, drug loading, and release behaviour. Then their cytotoxicity was evaluated by MTT assay against an HER-2-positive cell line, BT-474, and an HER-2-negative cell line, MDA-MB-468. The cellular uptake was studied by flow cytometry and fluorescent microscope. The particle size of NPs was in an appropriate range, with relatively high drug entrapment and acceptable release efficiency. The results showed no cytotoxicity for the polymer, but the significant increment of cytotoxicity was observed by treatment with docetaxel-loaded NPs in both HER-2-positive and HER-2-negative cell lines, in comparison with the free drug. The trastuzumab-targeted NPs also significantly enhanced cytotoxicity against BT-474 cells, compared with non-targeted NPs.

Redox Sensitive Polysaccharide Based Nanoparticles for Improved Cancer Treatment: A Comprehensive Review.

BACKGROUND: Among the numerous bio-responsive polymeric drug delivery systems developed recently, redox-triggered release of molecular payloads have gained great deal of attention, especially in the field of anticancer drug delivery. In most cases, these systems rely on disulfide bonds located either in the matrix crosslinks, or in auxiliary chains to achieve stimuli-responsive drug release. These bonds keep their stability in extracellular environments, yet, rapidly break by thiol-disulfide exchange reactions in the cytosol, due to the presence of greater levels of glutathione. Polysaccharides are macromolecules with low cost, natural abundance, biocompatibility, biodegradability, appropriate physical and chemical properties, and presence of numerous functional groups which facilitate chemical or physical cross-linking. METHODS: With regards to the remarkable advantages of polysaccharides, in the current study, various polysaccharide-based redox-responsive drug delivery systems are reviewed. In most cases the in vitro/in vivo effects of the developed system were also evaluated. RESULTS: Considering the hypoxic and reducing nature of the tumor microenvironment, with several folds higher glutathione levels than the systemic tissues, redox-sensitive polymeric systems could be implemented for tumorspecific drug delivery and the results of the previous researches in this field indicated satisfactory achievements. CONCLUSION: According to the reviewed papers, the efficiency of diverse redox-responsive polysaccharide-based nanoparticles with therapeutic payloads in cancer chemotherapy could be concluded. Nevertheless, more comprehensive studies are required to understand the exact intracellular and systemic fate of these nano-carriers, as well as their clinical efficacy for cancer treatment.

Crystal Engineering for Enhanced Solubility and Bioavailability of Poorly Soluble Drugs.

BACKGROUND: Crystal engineering is dealing with the creation of new structures and new properties in drug molecules through inter-molecular interactions. Researchers of pharmaceutical sciences have used this knowledge to alter the structure of crystalline medications in order to remedy the problems of more than 40% of the new designed drugs which suffer from low solubility and consequently, low bioavailability which have limited their clinical application. METHODS: This review covers a broad spectrum of aspects of the application of crystal engineering in pharmaceutics and includes a comprehensive wide range of different techniques used in crystal engineering of active pharmaceutical ingredients (API) to compensate the low water solubility and bioavailability of drugs related specially to class II of biopharmaceutical classification system (BCS). RESULTS: These techniques include; crystalline habit modification, polymorphism, solvates and hydrates, cocrystals, surface modification, crystallization, spherical agglomeration, liquisolid crystals and solid dispersions which are introduced and discussed in this review article. CONCLUSION: Each of these techniques has advantages and limitations which are emphasized on them.

Pharmacokinetics and in vitro/in vivo antitumor efficacy of aptamer-targeted Ecoflex® nanoparticles for docetaxel delivery in ovarian cancer.

PURPOSE: Epithelixal ovarian cancer is the fourth cause of cancer death in developed countries with 77% of ovarian cancer cases diagnosed with regional or distant metastasis, with poor survival rates. Docetaxel (DTX) is a well-known anticancer agent, with clinically proven efficacy in several malignancies, including ovarian cancer. However, the adverse effects caused by the active ingredient or currently marketed formulations could even deprive the patient of the advantages of treatment. Therefore, in the current study, polymeric nanoparticles (NPs) equipped with aptamer molecules as targeting agents were proposed to minimize the adverse effects and enhance the antitumor efficacy through directing the drug cargo toward its site of action. MATERIALS AND METHODS: Electrospraying technique was implemented to fabricate poly (butylene adipate-co-butylene terephthalate) (Ecoflex®) NPs loaded with DTX (DTX-NPs). Afterward, aptamer molecules were added to the DTX-NPs, which bound via covalent bonds (Apt-DTX-NPs). The particle size, size distribution, zeta potential, entrapment efficiency, and release profile of the NPs were characterized. Using MTT assay and flow-cytometry analysis, the in vitro cytotoxicity and cellular uptake of the NPs were compared to those of the free drug. Following intravenous administration of Taxotere®, DTX-NPs, and Apt-DTX-NPs (at an equivalent dose of 5 mg/kg of DTX), pharmacokinetic parameters and antitumor efficacy were compared in female Balb/c and HER-2-overexpressing tumor-bearing B6 athymic mice, respectively. RESULTS: The obtained results demonstrated significantly enhanced in vitro cytotoxicity and cellular uptake of Apt-DTX-NPs in a HER-2-overexpressing cell line, comparing to DTX-NPs and the free drug. The results of in vivo studies indicated significant increment in pharmacokinetic parameters including the area under the plasma concentration-time curve, mean residence time, and elimination half-life. Significant increment in antitumor efficacy was also observed, probably due to the targeted delivery of DTX to the tumor site and enhanced cellular uptake as evaluated in the aforementioned tests. CONCLUSION: Hence, the proposed drug delivery system could be considered as an appropriate potential substitute for currently marketed DTX formulations.

Supramolecular Self-Assembled Nanogels a New Platform for Anticancer Drug Delivery.

Polymer micellar nanogels are a group of core-shell polymeric micelles with swelling properties in aqueous media. Nanogel systems have proven their potential in controlled, sustained and targetable drug delivery area with no immunological responses. This review includes a comprehensive wide range of self-assembly of polymeric nanogels as delivery systems for anticancer drugs. Nanogels are nanoparticulate drug delivery systems which are specially designed for enhanced target oriented and cellular uptake of drugs with emphasis on chemotherapeutic agents studied in this review. Self-assembling nanogels are based on natural substances or synthetic polymers including: hyaluronic acid, heparin, alginate, cyclodextrins, chondroeitin sulfate, starch, mannan, chitosan, pullulan, poly(N-isopropylacrylamide), polyvynil alcohol, Pluronic F127, polyacrylic acid, poly(hydroxylethyl methacrylate), poly[2- (dimethylamino)ethyl methacrylate and polylactide-co-glycolide-polyethylen glycol amphiphilic di or tri block copolymer used to deliver anticancer drugs are introduced and discussed.

Lipoprotein Like Nanoparticles Used in Drug and Gene Delivery.

BACKGROUND: Native lipoproteins as nanoparticulate drug delivery systems have gained considerable attention in recent years. This is due to their biocompatibility, being endogenous, no triggering the immunological responses, relatively long half-life in the circulation, simple diffusion from vascular to extravascular compartments due to their nanometric particle size, potentially targeting capability to cellular receptors, simple preparative processes in the reconstituted forms, easy functionalization and high capacity for drug loading. Clinical application of many therapeutic agents like anticancer drugs and genes is hampered due to their susceptibility to degradation and difficult delivery into cells. Several nanoparticle platforms for siRNA delivery have been developed to overcome the major limitations facing the therapeutic uses of bioactive therapeutic agents. METHODS: This review covers a broad spectrum of lipoproteins as non-viral drug and gene delivery systems. These nanoparticles are developed for enhanced cellular uptake and specially targeted gene silencing in vitro and in vivo and their characteristics and opportunities for clinical applications of therapeutic agents are discussed in this article. Various types of lipoprotein nanovectors including: natural and modified lipoproteins used to deliver drugs, bioactive and genetic materials are introduced and the development of theranostics and combinational treatments are also discussed. RESULTS: The unique physicochemical properties of lipoproteins as natural nanostructures in biological systems and their structural diversity, including chylomicrons, VLDL, LDL and HDL, has caused their utility as potent pharmaceutical carriers. CONCLUSION: According to the literatures, different lipoproteins especially the artificial lipoproteins, reconstituted and modified ones have potential to be used in targeted delivery of therapeutic agents to the tumors and effective delivery of the corresponding genetic and other bioactive components involving in diseases.

Evaluation of cytotoxicity of Moringa oleifera Lam. callus and leaf extracts on Hela cells.

BACKGROUND: There are considerable attempts worldwide on herbal and traditional compounds to validate their use as anti-cancer drugs. Plants from Moringaceae family including Moringa oleifera possess several activities such as antitumor effect on tumor cell lines. In this study we sought to determine if callus and leaf extracts of M. oleifera possess any cytotoxicity. MATERIALS AND METHODS: Ethanol-water (70-30) extracts of callus and leaf of M. oleifera were prepared by maceration method. The amount of phenolic compounds of the extracts was determined by Folin Ciocalteu method. The cytotoxicity of the extracts against Hela tumor cells was carried out using MTT assay. Briefly, cells were seeded in microplates and different concentrations of the extract were added. Cells were incubated for 48 h and their viability was evaluated by addition of tetrazolium salt solution. After 3 h medium was aspirated, dimethyl sulfoxide was added and absorbance was determined at 540 nm with an ELISA plate reader. Cytotoxicity was considered when more than 50% reduction on cell survival was observed. RESULTS: Callus and leaf extracts of M. oleifera significantly decreased the viability of Hela cells in a concentration-dependent manner. However, leaf extract of M. oleifera were more potent than that of callus extract. CONCLUSION: As the content of phenolic compounds of leaf extract was higher than that of callus extract, it can be concluded that phenolic compounds are involved in the cytotoxicity of M. oleifera.