Advanced Targeted Drug Delivery of Fluoresceine Isothiocyanate by FOL-PEG-g-PEI-GAL conjugate as the Novel Nanoparticles

Abstract Polyethylenimine (PEI) is a well-known cationic polymer that has gained recent attention as a transfection and transduction agent. However; it is extremely cytotoxic in many cell lines because of its high surface charge (about +40 mV), non-biodegradability and non-biocompatibility. Other drawbacks of this polymer include, low duration of expression, non-specific cell uptake and instability in blood circulation. To enhance Polyethyleneimine biocompatibility, the graft pegylated copolymer was synthesized. To target cancer liver cells, two targeting ligands folic acid and galactose (lactobionic acid) were attached with graft Pegylated copolymer to increase specifically the entrance of this new targeted copolymer to cancer liver cells, because the folic acid and lactobionic acid receptors are over expressed only on human hepatocyte carcinoma. The composition of this new conjugated copolymer was characterized using 1H-NMR spectra. Its molecular weight and zeta potential were compared to polyethyleneimine. To study the entrance of this targeted carrier to human hepatocyte carcinoma (HepG2), fluoresceine isothiocyanate (FITC) as a model drug was conjugated to this novel carrier and the emission of green fluorescent was determined from three cell lines (HEK293, KB and HepG2) and compared with  fluoresceine isothiocyanate alone. Introduction: In recent years, there has been an enormous interest in the formulation of a targeted carrier for a specific population of cells, either locally or systematically. The targeted drug delivery system can be achieved by either non-polymeric or polymeric carrier methods.  Novel drug delivery by non-polymeric carriers has been studied for years; however, the broad use of this system is affected by the limited size of material delivered, cytotoxicity and no targeting interaction to certain cells. Polymeric drug delivery carriers have become a promising alternative since the carriers could be synthesized with higher purity and quality degree and less immunogenic response than the viral and lipidic carriers for drug targeting. Methods and results:  First of all, pegylated polyethylenimine (PEG-g-PEI) was synthesized and then folate-PEG-g-PEI, folate-PEG-g-PEI-galactose was prepared and folate-PEG-g-PEI-galactose conjugated with Fluorescein isothiocyanat as a model drug.          To investigate transduction efficacy of FOL-PEG-g-PEI-GAL conjugated with FITC, as a drug model, the fluorescent activity was measured in transduced HepG2, HEK293 and KB cell lines and the results are monitored

Determination of buprenorphine in raw material and pharmaceutical products using ion-pair formation

A simple and sensitive extractive spectrophotometric method has been described for the determination of buprenorphine either in raw material or in pharmaceutical formulations. The developed method is based on the formation of a colored ion-pair complex (1 : 1 drug/dye) of buprenorphine and bromocresol green (BCG) in buffer pH 3 and extracting in chloroform. The extracted complex shows absorbance maxima at 415 nm. Beer's law is obeyed in the concentration range of 1.32-100.81 μg mL−1 . The proposed method has been applied successfully for the determination of drug in commercial sublingual tablets and injectable dosage form. No significant interference was observed from the excipients commonly used as pharmaceutical aids with the assay procedure

Development and validation of a stability-indicating method for the quantitation of paclitaxel in pharmaceutical dosage forms

A simple, rapid stability-indicating isocratic assay has been developed and validated for the determination of Paclitaxel (PTX) in commercial injection formulations. The assay is performed using a Nucleosil RP-18 (5 µm, 250 × 4.0 mm i.d) column protected by a Nucleosil C18 precolumn (5 µm, 4.0 × 4.0 mm i.d.) with a mobile phase of methanol–water (80:20) and UV detection at 230 nm. The method was found to be specific for PTX in the presence of degradation products with an overall analytical run time of ~ 9 min. Accuracy reported as % bias was found to be 0.1–2.5% bias for all samples tested. Intra-assay precision (repeatability) was found to be 0.22–2.65% RSD, while inter-day precision (intermediate precision) was found to be 1.0–3.0% RSD for the samples studied. The calibration curve was found to be linear with the equation y = 29.78x + 7.65, and a linear regression coefficient of 0.9994 over the concentration range 0.05–20 µg/mL. The limits of quantitation and detection were 0.05 and 0.02 µg/mL, respectively. Taxol (30 mg/5 mL), a commercially available dosage form of PTX, was assayed and 100.6–103.6% of the label claim was recovered

Determination of Diclofenac on a Dysprosium Nanowire- Modified Carbon Paste Electrode Accomplished in a Flow Injection System by Advanced Filtering

A new detection technique called Fast Fourier Transform Square-Wave Voltammetry (FFT SWV) is based on measurements of electrode admittance as a function of potential. The response of the detector (microelectrode), which is generated by a redox processes, is fast, which makes the method suitable for most applications involving flowing electrolytes. The carbon paste electrode was modified by nanostructures to improve sensitivity. Synthesized dysprosium nanowires provide a more effective nanotube-like surface [1-4] so they are good candidates for use as a modifier for electrochemical reactions. The redox properties of diclofenac were used for its determination in human serum and urine samples. The support electrolyte that provided a more defined and intense peak current for diclofenac determination was a 0.05 mol L−1 acetate buffer pH = 4.0. The drug presented an irreversible oxidation peak at 850 mV vs. Ag/AgCl on a modified nanowire carbon paste electrode which produced high current and reduced the oxidation potential by about 100 mV. Furthermore, the signal-to-noise ratio was significantly increased by application of a discrete Fast Fourier Transform (FFT) method, background subtraction and two-dimensional integration of the electrode response over a selected potential range and time window. To obtain the much sensivity the effective parameters such as frequency, amplitude and pH was optimized. As a result, CDL of 2.0 × 10−9 M and an LOQ of 5.0 × 10−9 M were found for the determination for diclofenac. A good recovery was obtained for assay spiked urine samples and a good quantification of diclofenac was achieved in a commercial formulation

Resource allocation and purchasing arrangements to improve accessibility of medicines: Evidence from Iran

Objective: The aim of this study was to review the current methods of pharmaceutical purchasing by Iranian insurance organizations within the World Bank conceptual framework model so as to provide applicable pharmaceutical resource allocation and purchasing (RAP) arrangements in Iran. Methods: This qualitative study was conducted through a qualitative document analysis (QDA), applying the four-step Scott method in document selection, and conducting 20 semi-structured interviews using a triangulation method. Furthermore, the data were analyzed applying five steps framework analysis using Atlas-ti software. Findings: The QDA showed that the purchasers face many structural, financing, payment, delivery and service procurement and purchasing challenges. Moreover, the findings of interviews are provided in three sections including demand-side, supply-side and price and incentive regime. Conclusion: Localizing RAP arrangements as a World Bank Framework in a developing country like Iran considers the following as the prerequisite for implementing strategic purchasing in pharmaceutical sector: The improvement of accessibility, subsidiary mechanisms, reimbursement of new drugs, rational use, uniform pharmacopeia, best supplier selection, reduction of induced demand and moral hazard, payment reform. It is obvious that for Iran, these customized aspects are more various and detailed than those proposed in a World Bank model for developing countries

Pharmaceutical strategic purchasing requirements in Iran: Price interventions and the related effective factors

Objective: Pharmaceutical access for the poor is an essential factor in developing countries that can be improved through strategic purchasing. This study was conducted to identify the elements affecting price in order to enable insurance organizations to put strategic purchasing into practice. Methods: This was a qualitative study conducted through content analysis with an inductive approach applying a five-stage framework analysis (familiarization, identifying a thematic framework, indexing, mapping, and interpretation). Data analysis was started right after transcribing each interview applying ATLAS.ti. Data were saturated after 32 semi-structured interviews by experts. These key informants were selected purposefully and through snowball sampling. Findings: Findings showed that there are four main themes as Pharmaceutical Strategic Purchasing Requirements in Iran as follows essential and structural factors, international factors, economical factors, and legal factors. Moreover, totally 14 related sub-themes were extracted in this area as the main effective variables. Conclusion: It seems that paying adequate attention to the four present themes and 14 sub-themes affecting price can enable health system policy-makers of developing countries like Iran to make the best decisions through strategic purchasing of drugs by the main insurers in order to improve access and health in the country

Mu Opioid Receptor Gene: New Point Mutations in Opioid Addicts

Introduction: Association between single-nucleotide polymorphisms (SNPs) in mu opioid receptor gene and drug addiction has been shown in various studies. Here, we have evaluated the existence of polymorphisms in exon 3 of this gene in Iranian population and investigated the possible association between these mutations and opioid addiction.  Methods: 79 opioid-dependent subjects (55 males, 24 females) and 134 non-addict or control individuals (74 males, 60 females) participated in the study. Genomic DNA was extracted from volunteers’ peripheral blood and exon 3 of the mu opioid receptor gene was amplified by polymerase chain reaction (PCR) whose products were then sequenced.  Results: Three different heterozygote polymorphisms were observed in 3 male individuals: 759T>C and 877G>A mutations were found in 2 control volunteers and 1043G>C substitution was observed in an opioid-addicted subject. Association between genotype and opioid addiction for each mutation was not statistically significant.  Discussion: It seems that the sample size used in our study is not enough to confirm or reject any association between 759T>C, 877G>A and 1043G>C substitutions in exon 3 of the mu opioid receptor gene and opioid addiction susceptibility in Iranian population

Impact of Corporate Reputation on Brand Segmentation Strategy: An Empirical Study from Iranian Pharmaceutical Companies: Impact of Reputation on Pharmaceutical Brand Segmentation

The impact of corporate reputation uses, including value creation, corporate communication, and strategic resources on branding strategies such as segmentation and producing intangible assets for different industries is investigated in western countries in the past few years, but there is a gap for the generalizability of findings to countries out of the United States and Europe. To establish the western researcher‟s external validity of theories in other countries and to obtain a better understanding of the influences of branding and corporate reputation in pharmaceutical business markets, the researchers applied this study for Iran, as a country in the Middle East. The obtained results using SEM (by P.L.S. 2.0 software) showed a weak relation between value creation and brand segmentation (β = 3.007 and t-value = 1.806) and no significant relation between corporate communication and strategic resources with brand segmentation (β = 0.199 and t-value = 1.301) and (β = 3.046 and t-value = 1.465). Based on these findings; and previous researches in this field, it seems that pharmaceutical managers and marketers need to change their thoughts and practices regarding segmentation and reputation.This study is a pioneering attempt in Iran to evaluate the impact of corporate reputation on brand segmentation strategy