Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences最新文献

Drug-induced Stevens-Johnson syndrome (SJS) is a rare but life-threatening hypersensitivity reaction. Drug desensitization might be considered in drug-allergic patients with no therapeutic alternative. A 29-year-old man with a recent diagnosis of HIV and HBV (CD4 count: 4 cells/mm3) who has been receiving Trimethoprim/sulfamethoxazole (TMP/SMX) for Pneumocystis pneumonia (PCP) prophylaxis was admitted at Imam Khomeini hospital complex affiliated to Tehran University of Medical Sciences, with the diagnosis of SJS due to TMP/SMX. After 45 days of supportive care, the patient was a candidate for TMP/SMX desensitization due to our region's unavailability of alternative agents. A 9-day desensitization protocol was used, but the patient complained about diarrhea with severe pain in the rectal mucosa, and macules developed over his lips again on the third day. As a result, the desensitization process immediately stopped, and after the signs and symptoms were resolved, the patient was discharged with Clindamycin tablet 600 mg TDS. Unfortunately, two weeks after discharge, the patient experienced acute kidney injury (AKI) and expired after two dialysis sessions.

Purpose: Non-Alcoholic fatty liver disease is characterized by the accumulation of excess fat in the liver, chronic inflammation, and cell death, ranging from simple steatosis to fibrosis, and finally leads to cirrhosis and hepatocellular carcinoma. The effect of Fibroblast growth factor 2 on apoptosis and ER stress inhibition has been investigated in many studies. In this study, we aimed to investigate the effect of FGF2 on the NAFLD in-vitro model in the HepG2 cell line.

Methods: The in-vitro NAFLD model was first induced on the HepG2 cell line using oleic acid and palmitic acid for 24 h and evaluated by ORO staining and Real-time PCR. The cell line was then treated with various concentrations of fibroblast growth factor 2 for 24 h, total RNA was extracted and cDNA was consequently synthesized. Real-time PCR and flow cytometry was applied to evaluate gene expression and apoptosis rate, respectively.

Results: It was shown that fibroblast growth factor 2 ameliorated apoptosis in the NAFLD in-vitro model by reducing the expression of genes involved in the intrinsic apoptosis pathway, including caspase 3 and 9. Moreover, endoplasmic reticulum stress was decreased following upregulating the protective ER-stress genes, including SOD1 and PPARα.

Conclusions: FGF2 significantly reduced ER stress and intrinsic apoptosis pathway. Our data suggest that FGF2 treatment could be a potential therapeutic strategy for NAFLD.

Background: Cystic fibrosis is a severe, autosomal recessive disease that shortens life expectancy. According to studies, approximately 27% of patients with CF aged 2-5 years and 60 to 70% of adult patients are infected with P. aeruginosa. The patients experience bronchospasm leading to a persistent contracted state of the airways.

Objectives: The current work explores the possibility of combining ivacaftor and ciprofloxacin to combat the bacteria. A third drug L-salbutamol would be coated onto the surface of the drug-entrappped microparticles to instantaneously provide relief from bronchoconstriction.

Methods: The microparticles were prepared using bovine serum albumin and L-leucine using the freeze-drying approach. The process and formulation parameters were optimized. The prepared microparticles were surface coated by L-salbutamol using the dry-blending method. The microparticles were subjected to rigorous in-vitro characterization for entrapment, inhalability, antimicrobial activity, cytotoxicity study and safety. The performance of the microparticles to be loaded into a inhaler was checked by the Anderson cascade impactor.

Results: The freeze-dried microparticles had a particle size of 817.5 ± 5.6 nm with a polydispersity ratio of 0.33. They had a zeta potential of -23.3 ± 1.1 mV. The mass median aerodynamic diameter of the microparticles was 3.75 ± 0.07 μm, and the geometric standard diameter was 1.66 ± 0.033 μm. The microparticles showed good loading efficiency for all three drugs. DSC, SEM, XRD, and FTIR studies confirmed the entrapment of ivacaftor and ciprofloxacin. SEM and TEM scans observed the shape and the smooth surface. Antimicrobial synergism was proven by the agar broth, and dilution technique and the formulation was deemed safe by the results of the MTT assay.

Conclusion: Freeze-dried microparticles of ivacaftor, ciprofloxacin, and L-salbutamol could pave way to a hitherto unexplored combination of drugs as a novel approach to treat P. aeruginosa infcetions and bronchoconstriction commonly associated with cystic fibrosis.

Background: Recently biodegradable nanoparticles are the center of attention for the development of drug delivery systems. Molecularly imprinted polymer (MIP) is an interesting candidate for designing drug nano-carriers. MIP-based nanoparticles could be used for cancer treatment and exhibited the potential to fill gaps regarding to ligand-based nanomaterials. Also, the presence of a cross-linker can play an essential role in nanoparticle stability and physicochemical properties of nanoparticles after synthesis.

Objectives: In this research, a biodegradable drug delivery system based on MIP nanoparticles was prepared using a biodegradable cross-linker (dimethacryloyl hydroxylamine, DMHA) for methotrexate (MTX). A hydrolysable functional group CO-O-NH-CO was added to the crosslinking agent to increase the final biodegradability of the polymer.

Methods: Firstly, a biodegradable cross-linker was synthesized. Then, the non-imprinted polymers were prepared through mini-emulsion polymerization in the absence of a template; and efficient particle size distribution was determined. Finally, methotrexate was placed in imprinted polymers to achieve the desired MIP. Different types of MIPs were synthesized using different molar ratios of template, cross-linker, and functional monomer, and the optimal molar ratio was obtained at 1:4:20, respectively.

Results: HNMR successfully confirmed the chemical structure of the cross-linker. According to SEM images, nanoparticles had a spherical shape with a smooth surface. The imprinted nanoparticles showed a narrow size distribution with an average of 120 nm at a high ratio of cross-linker. The drug loading and entrapment efficiency were 6.4% and 92%, respectively. The biodegradability studies indicated that the nanoparticles prepared by DMHA had a more degradability rate than ethylene glycol dimethacrylate as a conventional cross-linker. Also, the polymer degradation rate was higher in alkaline environments. Release studies in physiological and alkaline buffer showed an initial burst release of a quarter of loaded MTX during the day and a 70% release during a week. The Korsmeyer-Peppas model described the release pattern. The cytotoxicity of MTX loaded in nanoparticles was studied on the MCF-7 cell line, and the IC₅₀ was 3.54 μg/ml.

Conclusion: It was demonstrated that nanoparticles prepared by DMHA have the potential to be used as biodegradable drug carriers for anticancer delivery. Synthesis schema of molecular imprinting of methotrexate in biodegradable polymer based on dimethacryloyl hydroxylamine cross-linker, for use as nanocarrier anticancer delivery to breast tumor.

Purpose: Association between vitamins C (VC)/ E (VE) and cancer survival is inconsistent. This systematic review is aimed to summarize trials for effects of VC/VE on cancer survival.

Methods: Relevant English trials were retrieved from PubMed, Cochrane Library, Embase, Web of Science, Scopus databases, and Clinicaltrials.gov through 21/June/2022. Inclusion criteria were all trials which assessed sole/combinations intake of VC/VE on survival rate, mortality, or remission of any cancer. Exclusion criteria were observational and animal studies.

Results: We reached 30 trials conducted on 38,936 patients with various cancers. Due to severe methodological heterogeneity, meta-analysis was impossible. High dose VC + chemotherapy or radiation was safe with an overall survival (OS) 182 days - 21.5 months. Sole oral or intravenous high dose VC was safe with non-significant change in OS (2.9-8.2 months). VE plus chemotherapy was safe, resulted in stabling diseases for 5 years in 70- 86.7% of patients and OS 109 months. It was found 60% and 16% non-significant reductions in adjusted hazard ratio (HR) deaths or recurrence by 200 mg/d tocotrienol + tamoxifen in breast cancer, respectively. Sole intake of 200-3200 mg/d tocotrienol before resectable pancreatic cancer was safe and significantly increased cancer cells' apoptosis. Combination VC and VE was non-significantly reduced 7% in rate of neoplastic gastric polyp.

Conclusion: Although our study is supported improvement of survival and progression rates of cancers by VC/VE, more high quality trials with large sample sizes are required to confirm.

Prospero registration number: CRD42020152795.

Background: Metabolic syndrome (MetS) is a risk factor for prostate cancer (PCa) progression. Thus, this life-threatening disease demands a proactive treatment strategy. Andrographis paniculata (AP) is a promising candidate with various medicinal properties. However, the bioactivity of AP is influenced by its processing conditions especially the extraction solvent.

Objective: In the present study, bioassay-guided screening technique was employed to identify the best AP extract in the management of MetS, PCa, and MetS-PCa co-disease in vitro.

Methods: Five AP extracts by different solvent systems; APE1 (aqueous), APE2 (absolute methanol), APE3 (absolute ethanol), APE4 (40% methanol), and APE5 (60% ethanol) were screened through their phytochemical profile, in-vitro anti-cancer, anti-obese, and anti-hyperglycemic properties. The best extract was further tested for its potential in MetS-induced PCa progression.

Results: APE2 contained the highest andrographolide (1.34 ± 0.05 mg/mL) and total phenolic content (8.85 ± 0.63 GAE/gDW). However, APE3 has the highest flavonoid content (11.52 ± 0.80 RE/gDW). APE2 was also a good scavenger of DPPH radicals (EC₅₀ = 397.0 µg/mL). In cell-based assays, among all extracts, APE2 exhibited the highest antiproliferative activity (IC₅₀ = 57.5 ± 11.8 µg/mL) on DU145 cancer cell line as well as on its migration activity. In in-vitro anti-obese study, all extracts significantly reduced lipid formation in 3T3-L1 cells. The highest insulin-sensitizing and -mimicking actions were exerted by both APE2 and APE3. Taken together, APE2 showed collectively good activity in the inhibition of PCa progression and MetS manifestation in vitro, compared to other extracts. Therefore, APE2 was further investigated for its potential to intervene DU145 progression induced with leptin (10-100 ng/mL) and adipocyte conditioned media (CM) (10% v/v). Interestingly, APE2 significantly diminished the progression of the cancer cell that has been pre-treated with leptin and CM through cell cycle arrest at S phase and induction of cell death.

Conclusion: In conclusion, AP extracts rich with andrographolide has the potential to be used as an alternative to ameliorate PCa progression induced by factors highly expressed in MetS.

Introduction: Super-paramagnetic iron oxide nanoparticles (SPIONs) are known as promising theranostic nano-drug carriers with magnetic resonance imaging (MRI) properties. Applying the herbaceous components with cytotoxic effects as cargos can suggest a new approach in the field of cancer-therapy. In this study mesoporous silica coated SPIONs (mSiO2@SPIONs) containing curcumin (CUR) and silymarin (SIL) were prepared and evaluated on breast cancer cell line, MCF-7.

Methods: Nanoparticles (NPs) were formulated by reverse microemulsion method and characterized by DLS, SEM and VSM. The in vitro drug release, cellular cytotoxicity, and MRI properties of NPs were determined as well. The cellular uptake of NPs by MCF-7 cells was investigated through LysoTracker Red staining using confocal microscopy.

Results: The MTT results showed that the IC50 of CUR + SIL loaded mSiO2@SPIONs was reduced about 50% in comparison with that of the free drug mixture. The NPs indicated proper MRI features and cellular uptake through endocytosis.

Conclusion: In conclusion the prepared formulation may offer a novel theranostic system for breast cancer researches.

Purpose: Affordable access to quality medicines is a critical target of global efforts to achieve universal health coverage. The aim of this study is to measure the affordability and accessibility of cardiovascular medicines in the city of Herat, Afghanistan.

Methods: The price, affordability, and availability data for 18 most sold generic (MSG) and lowest priced generic (LPG) products were collected from public and private pharmacies located in Herat city in Afghanistan in 2020, which in each area, six pharmacies were randomly selected from a combination of public and private ones based on the standardized methodology developed by WHO/HAI. According to this methodology on Medicine Prices, Accessibility, and Affordability, the minimum daily wage of an unskilled governmental worker, and the price of each type of cardiovascular medicines for one-month use were calculated separately. If the cost of the treatment was more than the minimum daily wage, the medicine was considered unaffordable.

Results: The mean availability score for lowest price generic (LPG) in public and private pharmacies and based on the countries of origin including Iran, Pakistan, and India was 60%, 46%, and 31%, respectively. Of the 18 medicines surveyed, just Atenolol (Iranian brand) was found in all 30 pharmacies on the day of data collection. All Indian- brand medicines were less than fifty percent available in any of the surveyed public and private pharmacies. Among the medicines exported to Afghanistan, the population of Herat used more medicines made by Pakistan compared to India and Iran (MSG). Indian medicines were the most expensive ones and the Iranian medicines were the cheapest. A wage of less than one day was enough to afford one-month supply of generic medicines at the lowest price.

Conclusion: Access of patients to cardiovascular medicines in Afghanistan was 46% in this study which is regarded as low access. Most of available cardiovascular medicines in the market of this country were made in Iran, Pakistan and India. Although the Iranian ones were the cheapest, but people used more Pakistani medicines. LPG products were affordable to the studied population.

Objectives: Scutellaria baicalensis (SB) has been traditionally used to combat a variety of conditions ranging from ischemic heart disease to cancer. The protective effects of SB are due to the action of two main flavonoids baicalin (BA) and baicalein (BE). This paper aimed to provide a narrative review of the protective and antidotal effects of SB and its main constituents against natural toxicities and physical hazards.

Evidence acquisition: Scientific databases Medline, Scopus, and Web of Science were thoroughly searched, based on different keywords for in vivo, in vitro and clinical studies which reported protective or therapeutic effects of SB or its constituents in natural and physical toxicities.

Results: Numerous studies have reported that treatment with BE, BA, or total SB extract prevents or counteracts the detrimental toxic effects of various natural compounds and physical hazards. The toxic agents include mycotoxins, lipopolysaccharide, multiple plants and animal-derived substances as well as physical factors which negatively affected vital organs such as CNS, liver, kidneys, lung and heart. Increasing the expression of radical scavenging enzymes and glutathione content as well as inhibition of pro-inflammatory cytokines and pro-apoptotic mediators were important mechanisms of action.

Conclusion: Different studies on the Chinese skullcap have exhibited that its total root extract, BA or BE can act as potential antidotes or protective agents against the damage induced by natural toxins and physical factors by alleviating oxidative stress and inflammation. However, the scarcity of high-quality clinical evidence means that further clinical studies are required to reach a more definitive conclusion.

Objectives: With increasing awareness of the potential adverse impact of conventional surfactants on the environment and human health, there is mounting interest in the development of bio-based surfactants (which are deemed to be safer, more affordable, are in abundance, are biodegradable, biocompatible and possess scalability, mildness and performance in formulation) in personal care products.

Method: A comprehensive literature review around alkyl polyglucosides (APGs) and sucrose esters (SEs) as bio-based surfactants, through the lens of the 12 green chemistry principles was conducted. An overview of the use of bio-based surfactants in personal care products was also provided.

Results: Bio-based surfactants are derived primarily from natural sources (i.e. both the head and tail molecular group). One of the more common types of bio-based surfactants are those with carbohydrate head groups, where alkyl polyglucosides (APGs) and sucrose esters (SEs) lead this sub-category. As global regulations and user mandate for sustainability and safety increase, evidence to further support these bio-based surfactants as alternatives to their petrochemical counterparts is advantageous. Use of the green chemistry framework is a suitable way to do this. While many of the discussed principles are enforced industrially, others have only yet been applied at a laboratory scale or are not apparent in literature.

Conclusion: Many of the principles of green chemistry are currently used in the synthesis of APGs and SEs. These and other bio-based surfactants should, therefore, be considered suitable and sustainable alternatives to conventional surfactants. To further encourage the use of these novel surfactants, industry must make an effort to implement and improve the use of the remaining principles at a commercial level.