Advanced Pharmaceutical Bulletin
Volume:11 Issue: 2, Feb 2021

In recent years, high atomic number nanoparticles (NPs) have emerged as promising radio-enhancer agents for cancer radiation therapy due to their unique properties. Multi-disciplinary studies have demonstrated the potential of NPs-based radio-sensitizers to improve cancer therapy and tumor control at cellular and molecular levels. However, studies have shown that the dose enhancement effect of the NPs depends on the beam energy, NPs type, NPs size, NPs concentration, cell lines, and NPs delivery system. It has been believed that radiation dose enhancement of NPs is due to the three main mechanisms, but the results of some simulation studies failed to comply well with the experimental findings. Thus, this study aimed to quantitatively evaluate the physical, chemical, and biological factors of the NPs. An organized search of PubMed/Medline, Embase, ProQuest, Scopus, Cochrane and Google Scholar was performed. In total, 77 articles were thoroughly reviewed and analyzed. The studies investigated 44 different cell lines through 70 in-vitro and 4 in-vivo studies. A total of 32 different types of single or core-shell NPs in different sizes and concentrations have been used in the studies.

Parkinson’s disease (PD) is a neurodegenerative disorder which is characterized by typical symptoms including gradual progressive muscle rigidity, tremor and loss of motor skills. Although there is no definitive cure for PD, the extract of some medicinal plants and their ingredients have been suggested to relieve its symptoms and to prevent disability in patients. This review is focused on therapeutic effects of some medicinal plants and their ingredients on PD. The findings presented in this review were collected from experimental and clinical studies in databases including PubMed, Web of Science and Google Scholar until the end of May 2019. The keywords "neurotoxicity " or "Parkinson’s disease" or "neuroprotective" and "Medicinal plants" and "Flavonoids" were searched. Based on the results of animal and clinical studies, the extract of medicinal plants and their components which are discussed in this review have neuro-protective effects against PD. These protective properties mainly are mediated through inhibition of dopamine metabolizing enzymes, reduction oxidant markers, increase of antioxidant agents and suppression of neuro-inflammation.

Colorectal cancer is one of the most disseminated diseases across the globe engaging the digestive system. Various therapeutic methods from traditional to the state-of-the-art ones have been applied in CRC patients, however, the attempts have been unfortunate to lead to a definite cure. MiRNAs are a smart group of non-coding RNAs having the capabilities of regulating and controlling coding genes. By utilizing this stock-in-trade biomolecules, not only disease’s symptoms can be eliminated, there may also be a good chance for the complete cure of the disease in the near future. Herein, we provide a comprehensive review delineating the therapeutic relationship between miRNAs and colorectal cancer. To this, various clinical aspects of miRNAs which act as a tumor suppressor and/or an oncogene, their underlying cellular processes and clinical outcomes, and, in particular, their effects and expression level changes in patients treated with chemo- and radiotherapy are discussed. Finally, based on the results deducted from scientific research studies, therapeutic opportunities based on targeting/utilizing miRNAs in the preclinical as well as clinical settings are highlighted.

The topical delivery offers numerous benefits, such as the ability to deliver drugs specifically on site selectively, prevents fluctuations in the levels of the drug, improved compliance, and improved self-medication capacity. Skin is the main route of the administration of the drug delivery system and burns mainly cause skin damage. A burn is a kind of damage caused to skin and tissues by fire, ice, electrical energy, pollutants, friction, and radiation. There are three different types of burns, including superficial epidermis burns, partial-thickness dermis that stretch to the papillary and reticular dermis, and full-thickness burns that cover the dermis whole. The objective of the present review article is to focus on fabrication techniques of medical textiles, different types of polymers used for designing medicated textiles, skin burn conditions, and application of medicated textiles for treatment of burn along with other applications. Cream, ointment, and gel are the dosage forms used in burns. Intravenous fluids, wound care, assorted antibiotics, surgical and alternative medicines, burned creams and salami, dressings can be used to treat wounds. Nanofibers are nanometer-specific fibers that encapsulate drugs inside them and cure wounds. Nanofibers have all the properties that speed up wound healing. The properties are mechanical integrity, proper timing of wound addiction, temperature homeostasis facilitation and gas exchange, absorption of exudates. The nanofibers have been used in burn care and have been highly efficient and non-toxic.

Followed by developing modern medicine, leeches did not have extensive use as before; however, in the late 19th century, they were still used in most countries all over the world. Thus far, leeches were utilized in treating various diseases like skin disorders, arthritis, and cancer. In Egypt, using leeches for treatment dates back to early 1500 BC. A medical leech’s salivary glands involve over 100 bioactive proteins and the salivary gland secretion contains bacteriostatic, analgesic, and anticoagulation influences; with resolving activity, it causes microcirculation disorders elimination, restoring the hurt vascular permeability of organs and tissues, removing hypoxia, decreasing blood pressure and detoxifying the organism by antioxidant paths. The current work reviews the innovative treatment with medical leech, especially proteins in leech saliva extraction (LSE) with high potential in medicine. The virtue of salivary gland secretions which are proteinaceous enzymes, leech acts on various diseases such as venous congestion in reconstructive and plastic surgery, osteoarthritis, cardiovascular diseases caused by blood coagulation disorders, pain management, priapism, macroglossia, cancer complications, wounds and many other. To confirm the potential therapeutic impacts of leech treatment, more studies are required in more extensive areas with more exact methodologies.

This study aimed to evaluate the role of magnetic liposome nanoparticles (ML NPs) as a carrier for paclitaxel (PTX) for the treatment of ovarian cancer in vitro.

Magnetic NPs (MNPs) were synthesized by chemical co-precipitation method. The resulting NPs were characterized in terms of size, size distribution, zeta potential, drug encapsulation efficiency, drug release pattern, and cytotoxicity effects.

The size and zeta potential of PTX-PEG-L and PTX-PEG-ML NPs were determined to be 296, 198 nm; -20, and -19 mV, respectively. Also, their drug encapsulation efficiencies were determined to be 97 and 96%, respectively. It was found that PTX-PEG-ML NPs, compared to PTX-PEG-L NPs, caused a reduction (11 %) in the rate of drug release. The cytotoxicity of the drug-loaded NPs was assessed using 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay against human ovarian epithelial cancer (A2780CP) cells, and the results demonstrated that PTX-PEG-ML NPs caused higher cytotoxicity (by 14%) compared to PTX-PEG-L NPs (IC50: 1.88 ± 0.09 and 2.142 ± 0.1 µM, respectively).

Overall, the results of this study suggest that PTX-PEG-ML NPs could be considered as a therapeutic candidate for the treatment of ovarian cancer.

Microemulsion (ME) achieved progressing consequences on both the research and industry levels due to their distinctive properties. ME based-limonene system is considered as a surrogate to the traditional microemulsion composed of conventional oils. Thus, a novel microemulsion based on D-limonene and Gelucire®44/12 had been designed and evaluated with assessing the factors affecting its physicochemical characteristics and in vivo skin irritation.

The impact of microemulsion components and ratios on the isotropic region of the pseudo-ternary phase diagram was investigated. The optimal formula was evaluated in terms of percentage transmittance, average globule size, size distribution, zeta potential, microscopical morphology, stability under different storage conditions and its effect on the mice ear skin.

The results demonstrated that Labrasol® and Labrafil® M 1944 CS had been selected as surfactant and co-surfactant, respectively, due to their emulsifying abilities. The largest isotropic area in the pseudo-ternary phase diagram was at a weight ratio of 4:1 for Labrasol® and Labrafil® M 1944 CS. The optimized microemulsion with 25% w/w of the lipid phase and 58.3% w/w of the aqueous phase displayed an optical transparency of 96.5±0.88 %, average globule size of 125±0.123 nm, polydispersity index of 0.272±0.009, zeta potential of -18.9± 2.79 mV with rounded globules morphology and high stability. The in vivo skin irritation and the histopathological evaluation of microemulsion elucidated its safety profile when applied on the skin.

The formulated microemulsion is a prospective aid for an essential oil to minimize its volatility, enhance its stability, and mask its dermal irritant

The prevalent types of idiopathic inflammatory bowel disease (IBD) are ulcerative colitis and Crohn’s disease, which affects a large number of populations. Budesonide (BUD) is a glucocorticoid with potent anti-inflammatory activity but low systemic efficacy because of high receptor affinity and rapid diversion. To overcome low efficacy and availability, a novel Budesonide nano-sponges was formulated using quasi- solvent diffusion and Eudragit S-100 as polymer. It was then investigated for the effect of process variables using Box-Behnken design.

The BUD Nano sponges were evaluated for particle size, particle size, polydispersity, percent drug entrapment, drug release pattern. The formulation was evaluated by an in vivo study using male Wistar rats and parameters such as clinical activity score (CAS), colon/body weight ratio (C/B ratio), macroscopic ulceration (damage score) activity were performed. Finally, histopathological examination was performed on colon tissue samples.

The formulation showed better efficacy and availability as compared with the available formulations of budesonide, which indicates the good efficacy of the formulated nanosponges. The clinical activity score was attenuated by the formulated nanosponges in the Wistar rats. The colon to body weight ratio was significantly reduced as compared with the control formulation. The histopathology of colon treated with nanosponges showed normal structure and architecture of the colon.

The results of the present work confirmed the utility of Budesonide nano-sponges as novel carriers in management inflammatory bowel disease.

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.

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.

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.

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.

Propolis is a resinous material obtained by honeybees with many biological and pharmacological properties which can be used for treatment of various diseases. Current study aims to formulate and characterize propolis-loaded solid lipid nanoparticles (SLNs) carrier system.

The prepared SLNs, composed of glyceryl monostearate (GMS), Soy lecithin, Tween 80 and polyethylene glycol 400 (PEG 400), were fabricated employing solvent emulsification-evaporation technique. In addition, the impact of several variables including concentration ratios of GMS/Soy lecithin and PEG 400/Tween 80 along with emulsification time were evaluated on the size, polydispersity index (PDI) and zeta potential of particles. SLN formulations were optimized using Box-Behnken design. The particles were freeze dried and morphologically studied by scanning electron microscopy (SEM). The in-vitro release profile of propolis entrapped in the optimized nanoparticles was investigated.

The mean particle size, PDI, zeta potential, entrapment efficiency (EE) and loading efficiency (LE) of optimized propolis-loaded SLNs were found to be 122.6±22.36 nm, 0.28±0.06, -26.18±3.3 mV, 73.57±0.86% and 3.29±0.27%, respectively. SEM images exhibited nanoparticles to be non-aggregated and in spherical shape. The in-vitro release study showed prolonged release of propolis from nanoparticles.

The results implied that the proposed way of SLN preparation could be considered as a proper method for production of propolis loaded colloidal carrier system.

the present study aimed to formulate PLGA and PLGA-PEG-Galactosamine NPs loaded with amphotericin B with appropriate physicochemical properties and antifungal activity. PLGA was functionalized with GalN to increase the adhesion and antifungal activity of NPs against Candida albicans.

the physicochemical properties of NPs were characterized by particle size determination, zeta potential, drug crystallinity, loading efficiency, dissolution studies, DSC, XRPD, and FT-IR. Antifungal activity of the NPs at different drug/polymer ratios was examined by determining MICs.

the FT-IR and 1HNMR analysis successfully confirmed the formation of PLGA- PEG-GalN NPs. The PLGA NPs were in the size range of 174.1 ± 3.49 to 238.2±7.59 nm while PLGA-GalN NPs were 255.6 ±4.08 nm in size, respectively. Loading efficiency was in the range of 67%±2.4 to 77%±1.6, and entrapment efficiency in the range of 68.185%±1.9 to 73.05%±0.6. Zeta potential and loading efficiency for PLGA-GalN NPs were –0.456, 71%. The NPs indicated an amorphous status according to XRPD patterns and DSC thermograms. The PLGA-PEG-GalN NPs showed higher fungistatic activity than PLGA NPs.

the results demonstrated that the antifungal activity of PLGA-PEG-GalN NPs was higher than pure amphotericin B and PLGA NPs.

The main objective of the present study was to develop the colonic delivery system for 5-Aminosalicylic acid (5-ASA) as an anti-inflammatory drug.

Matrix pellets containing various proportions of alginate, calcium and Eudragit® RS were prepared by Extrusion-Spheronization technique. Thermal treatment was used to investigate the effect of the curing process on the surface morphology, mechanical and physicochemical properties and in vitro drug release profile of pellets. Based on the obtained results optimal formulations were selected to coating by the Eudragit® RS and subjected to a subsequent continuous dissolution test.

Image analysis and also scanning electron microscopy results proved acceptable morphology of the pellets. The fourier transform infrared spectroscopy and differential scanning calorimetry studies ruled out any interactions between the formulation’s components. Curing process did not alter the mechanical properties of pellets. The release rate of the drug from matrices was prolonged due to the decreased porosity of cured pellets. Furthermore, selected cured pellets which coated with Eudragit® RS, prevented undesired premature drug release.

Formulation containing 17.5% calcium, 17.5% alginate, and a coating level of 10% demonstrated enhanced drug release so that provided resistance to acidic conditions, allowing complete drug release in alkaline pH, mimicking colonic environment. The slow and consistent drug release from this formulation could be used for treatment of a broader range of IBD patients especially in whom colonic pH levels have been measured at lower than pH 7.0.

Foodborne diseases are still a serious problem in public health and natural compounds are being widely considered for their potential industrial protective additive in food products. Origanum vulgare L. has been known as an antimicrobial effective herb. This present study was carried out to examine the antimicrobial effect of O. vulgare essential oil nanoemulsion in comparison with conventional emulsion.

The essential oil was obtained by hydrodistillation, analyzed by GC-Mass and formulated as a nanoemulsion to improve water dispersion by high-energy emulsification method. The antimicrobial activity of the prepared formulation was assessed by measuring the minimum inhibitory concentration (MIC), minimum bactericidal/fungicidal concentration (MBC/MFC) and zone of inhibition against some main foodborne pathogen microorganisms.

The main component of the oregano essential oil was carvacrol (78%) and the selected nanoemulsion formulation demonstrated low polydispersity (0.11) and mean droplet (72.26 nm) and it was stable even after 30 days of storage. The nanoemulsion form displayed significant activity against the S. aureus, C. albicans and A. niger with inhibition zones ranging from 8.7–22.3mm. The MIC of nanoemulsion against the tested bacteria was within the range of 0.156 to 0.312 (mg/ml) and against the tested fungi were in the range of 0.078 to 0.156 (mg/ml). The MBC/MFC of nanoemulsion against the tested microorganisms were in the range of 0.312 to 5 (mg/ml).

The study's results demonstrated the possibility of using the nanoemulsion form of oregano essential oil as a food additive to inhibit the growth of some foodborne microorganisms and extending the shelf life of food products.

Transfusion of red blood cells (RBCs) is a supportive and common treatment in surgical care, trauma, and anemia. However, in vivo production of RBC seems to be a suitable alternative for blood transfusions due to the limitation of blood resources, the possibility of disease transmission, immune reactions, and the presence of rare blood groups. Cell cultures require serum-free or culture media supplemented with highly expensive animal serum, which can transmit xenoviruses. Platelet lysate (PL) can be considered as a suitable alternative containing a high level of growth factors and a low production cost.

Three-step culture media supplemented with PL or fetal bovine serum (FBS) were used for proliferation and differentiation of CD34+ umbilical cord blood stem cells to erythrocytes in co-culture with bone marrow mesenchymal stem cells (BM-MSCs). The cells were cultivated for 15 days and cell proliferation and expansion were assessed using cell counts at different days. Erythroid differentiation genes, CD71 and glycophorin A expression levels were evaluated.

Maximum hematopoietic stem cells (HSCs) proliferation was observed on day 15 in PL-containing medium (99±17×103-fold). Gene expression and surface markers showed higher differentiation of cells in PL-containing medium.

The results of this study indicate that PL can enhance erythroid proliferation and differentiation of CD34+ HSCs. PL can also be used as a proper alternative for FBS in the culture medium and HSCs differentiation.

CRISPR/Cas9 gene editing technology has revolutionized gene manipulation by providing the opportunity of gene knock out/in, transcriptional modification and base editing. The application of this system extended into different eras of biology, from cell development to animal modeling. Various generations of CRISPR technology have been developed to make genome editing easy which resulted in rapid protocols for amelioration of a large genome.

we established a simple protocol for gene manipulation in Chinese hamster ovary (CHO) cells to achieve a Caspase 7 deficient cell line by using combination of all-in-one CRISPR technology and CRISPR/ Cas9 homology-independent targeted integration (CRISPR HITI).

the findings of this study indicated that using CRISPR knocking in/out technology facilitates genomic manipulation in CHO cells. Integration of EGFP in target locus of caspase 7 gene made the selection of knockout CHO cell line easy which achieved by cell sorting and single-cell cloning.

this system introduces an effective targeting strategy for multiplex genome engineering, coinciding gene integration which simplified the selection of desired genomic characteristics.

The failure of chemotherapy in breast cancer is caused by breast cancer stem cells (BCSCs), a minor population of cells in bulk mammary tumors. Previously, hesperetin, a citrus flavonoid, showed cytotoxicity in several cancer cells and increased cytotoxicity of doxorubicin and cisplatin. Hesperetin also inhibited osteogenic and adipocyte differentiation, however, a study of the effect of hesperetin on BCSCs has not yet been performed.

In this study, we combined bioinformatics and in vitro works. A bioinformatic approach was performed to identify molecular targets, key proteins, and molecular mechanisms of hesperetin targeted at BCSCs, and genetic alterations among key genes. In addition, an in vitro study was carried out to measure the effects of hesperetin on BCSCs using the spheroids model of MCF-7 breast cancer cells (mammospheres).

Using a bioinformatics approach, we identified P53, PPARG, and Notch signaling as potential targets of hesperetin in inhibition of BCSCs. The in vitro study showed that hesperetin exhibits cytotoxicity on mammospheres, inhibits mammosphere and colony formation, and inhibits migration. Hesperetin modulates the cell cycle and induces apoptosis in mammospheres. Moreover, hesperetin treatment modulates the expression of p53, PPARG, and NOTCH1.

Taken together, hesperetin has potential for the treatment of BCSC by targeting p53, PPARG and Notch signaling. Further investigation of the molecular mechanisms involved is required for the development of hesperetin as a BCSC-targeted drug.

Reovirus type 3 Dearing (ReoT3D), a wild type oncolytic virus (OV) from the Reoviridae family, kills KRAS mutant cancer cells. However, the use of oncolytic viruses (OVs) has faced with some limitations such as immune responses, and delivery of OVs to the tumor sites in systemic therapy. To solve this, and also to increase the anti-cancer effects of these OVs, mesenchymal stem cells (MSCs) might be used as an effective vehicle for OVs delivery. In this study, we examined the anti-cancer effects of human Adipose Derived-MSCs (AD-MSCs) as a vehicle of ReoT3D against human gliobastoma cells.

Here, AD-MSCs were characterized and toxicity of ReoT3D on them was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Then, capability of AD-MSCs for virus production was assessed by real-time PCR, and different in vitro anti-cancer experiments were applied for our anti-cancer purposes.

Our results from toxicity assay revealed that the isolated and provoked AD-MSCs were resistant to nontoxic concentration multiplicity of infection (MOI) >1 pfu/cells of ReoT3D. In addition, the results indicated that AD-MSCs were susceptible for virus life cycle complementation and were capable for production of virus progenies. Furthermore, our results showed that AD-MSCs had oncolysis effects and increased the anti-cancer effects of ReoT3D.

AD-MSCs as a susceptible host for oncolytic reovirus could increase the anti-cancer activity of this OV against glioblastoma multiforme (GBM) cell line.

Type 1 diabetes mellitus (T1DM) has dramatically increased in recent years, especially in young people, and limits the life quality of the patients involved. Thus, many researchers are performing extensive studies to find alternative treatments for DM.

Here, we evaluated the improvement effects of the heat-killed Actinomycetales species, including Gordonia bronchialis, and Tsukamurella inchonensis in streptozotocin-diabetic rats by biochemical, immunological, and histopathological examinations.

The present findings exhibited a dramatic and progressive alteration in the serum levels of IL-6, IL-10 and TNF-α in the diabetic group, which were related to the blood glucose and insulin levels, oxidative stress defense (evaluated by TAC and MDA activities), and the pancreas biochemical indicators (such as amylase and lipase). More importantly, the present results were consistent with the histopathological findings, which included cellular degeneration, vascular congestion, hemorrhage, focal necrosis associated with mononuclear cell infiltration. Interestingly, all of the diabetic changes in the blood serum and tissues improved remarkably in the treated groups by Actinomycetales species.

Surprisingly, most of the current diabetic complications effectively attenuated after oral administration of both Actinomycetales species, particularly with a high dose of T. inchonensis. Thus, it is concluded that the heat-killed Actinomycetales species can prevent and improve the progression of T1DM and its various complications profoundly.

There are number of reports available regarding defensins activity against mammalian cells besides their antimicrobial and immune regulatory activities. This study aims to investigate anticancer and apoptosis activity of the purified defensins from leukodepletion filters alone or in synergism with bacterial peptide, nisin, on prostate and colorectal cancer.

Leucoflex LCR-5 filters were backflushed by an optimized elution system. Isolated granulocytes were sonicated and the supernatant treated before further purification by HPLC. SDS-PAGE and western blot testing verified the fraction. Cell culture on PC-3 (human prostate adenocarcinoma), and HCT-116 (human colorectal carcinoma) were conducted following by MTT assays in addition to annexin flow cytometry for sole and synergistic effects with peptide nisin.

Viable and active neutrophils could recover, and α-defensins were extracted and purified. Combinations of an optimal dose of α-defensins and nisin showed a remarkable synergistic effect on cancer cell lines (over 90% and 70% for PC-3 and HCT-116, respectively).

It also observed that less than 40% of both cells could survive after co-treatment with optimal dose. Also, apoptosis was increased after treatment by these peptides together. Annexin Vpositive populations significantly increased in percentage in comparison with control.

Tumor vascular targeting (TVT) appeared as an appealing approach to fight cancer, though, the results from the clinical trials and drugs in the market were proved otherwise. The promise of anti-angiogenic therapy as the leading TVT strategy was negatively affected with the discovery that tumor vascularization can occur non-angiogenic mechanisms such as co-option. An additional strategy is induction of tumor vascular infarction and ischemia.

Such that we used truncated coagulase (tCoa) coupled to tumor endothelial targeting moieties to produce tCoa-NGR fusion proteins. We showed that tCoa-NGR can bypass coagulation cascade to induce selective vascular thrombosis and infarction of mild and highly proliferative solid tumors in mice. Moreover, combination therapy can be used to improve the potential of cancer vascular targeting modalities. Herein, we report combination of tCoa-NGR with vascular disrupting agent, Vadimezan.

Our results show that synergistic work of these two agents can significantly suppress growth of B16-F10 melanoma tumors in C57/BL6 mice.

For the first time, we used the simultaneous benefits of two strategies for inducing thrombosis and destruction of tumor vasculature as spatial co-operation. The tCoa-NGR induce thrombosis which reduces blood flow in the peripheral tumor region. And combined with the action of DMXAA, which target inner tumor mass, growth and proliferation of melanoma tumors can be significantly suppressed.