Biochemically Altered Human Erythrocytes as a Carrier for Targeted Delivery of Primaquine: an In Vitro Study

Fars K. Alanazi,Ibrahim A. Alsarra,Gamal El-Din I. Harisa,Ahmad Maqboul,Magdi Abdel-Hamid,Steven H. Neau 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.4

The aim of this study was to investigate human erythrocytes as a carrier for targeted drug delivery of primaquine (PQ). The process of PQ loading in human erythrocytes, as well as the effect of PQ loading on the oxidative status of erythrocytes, was also studied. At PQ concentrations of 2, 4, 6, and 8 mg/mL and an incubation time of 2 h, the ratios of the concentrations of PQ entrapped in erythrocytes to that in the incubation medium were 0.515, 0.688, 0.697 and 0.788, respectively. The maximal decline of erythrocyte reduced glutathione content was observed at 8 mg/mL of PQ compared with native erythrocytes p < 0.001. In contrast, malondialdehyde and protein carbonyl were significantly increased in cells loaded with PQ (p < 0.001). Furthermore, osmotic fragility of PQ carrier erythrocytes was increased in comparison with unloaded cells. Electron microscopy revealed spherocyte formation with PQ carrier erythrocytes. PQ-loaded cells showed sustained drug release over a 48 h period. Erythrocytes were loaded with PQ successfully, but there were some biochemical as well as physiological changes that resulted from the effect of PQ on the oxidative status of drugloaded erythrocytes. These changes may result in favorable targeting of PQ-loaded cells to reticulo-endothelial organs. The relative impact of these changes remains to be explored in ongoing animal studies.

Comparative Study of Itraconazole-Cyclodextrin Inclusion Complex and Its Commercial Product

Ibrahim A. Alsarra,Fars K. Alanazi,Sayed M. Ahmed,Ahmed A. Bosela,Suliman S. Alhamed,Hammam A. Mowafy,Steven H. Neau 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.7

Itraconazole (ITZ) solid complex using hydroxypropyl-β-cyclodextrin (ITZ-HP-β-CD) with 20% polyvinylpyrrolidone was prepared by a co-evaporation method. The complex improved antifungal activity against C. parapasilosis and C. albicans. The complex demonstrated good flow and compressibility characteristics. The complex was formulated as a capsule dosage form and drug release was evaluated. Capsules containing ITZ-HP-β-CD at a molar ratio of 1:3 with 20% polyvinylpyrrolidone have a faster dissolution rate than commercial capsules (Sporanox ®). About 88% of ITZ was released in less than 30 min and the initial dissolution rate exhibited a 3.5-fold increase compared to the commercial product. UV spectrophotometeric, HPLC, and antimicrobial methods were used to determine ITZ concentration in the release medium and the results obtained by these methods are reported. It was found that HPLC analysis is a suitable and reliable method for determination of the drug concentration with a coefficient of variation less than 10%. The intraday precision showed a coefficient of variation less than 3.96%, and that for interday was less than 4.99%. The HPLC method was more accurate and precise than the antimicrobial and UV-spectrophotometric methods for determination of ITZ concentration present in the release medium.

Solubility and thermodynamic function of apremilast in different (Transcutol + water) cosolvent mixtures: Measurement, correlation and molecular interactions

Faiyaz Shakeel,Nazrul Haq,Fars K. Alanazi,Ibrahim A. Alsarra 한국공업화학회 2017 Journal of Industrial and Engineering Chemistry Vol.56 No.-

The solubility of apremilast (APM) in different “Transcutol1+ water” cosolvent mixtures was determined and correlated at “T = 298.2 K–318.2 K” and ‘p = 0.1 MPa’. The experimental solubilities of APM were determined and correlated with “Apelblat, van’t Hoff, Yalkowsky and Jouyban–Acree equations”. The maximum solubilities of APM in mole fraction were obtained in neat Transcutol (2.53 102 at T = 318.2 K). Based on activity coefficients, strong molecular interactions were obtained between APM and neat Transcutol in comparison with APM and neat water. “Apparent thermodynamic analysis” showed an “endothermic and entropy-driven dissolution” of APM.

Erythrocyte-mediated Delivery of Pravastatin: In Vitro Study of Effect of Hypotonic Lysis on Biochemical Parameters and Loading Efficiency

Gamaleldin I. Harisa,Mohamed F. Ibrahim,Fars K. Alanazi 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.8

Exposure of erythrocytes to hypotonic lysis creates pores in the cell membrane, through which pravastatin can enter and become trapped, after resealing them with a suitable buffer. We investigated the effects of tonicity, incubation time and drug concentration on drug loading into erythrocytes. Furthermore, we investigate the effects of pravastatin on erythrocyte oxidative stress markers and osmotic fragility behavior. Encapsulation was achieved using buffer solutions of different tonicities (0.5, 0.6 and 0.7% NaCl) and different drug concentrations (2, 4, 8 and 10 mg/mL) for a range of incubation times (15, 30, 60 and 120 min). The results demonstrated that controlled hypotonic lysis could entrap pravastatin in human erythrocytes, with acceptable loading parameters. The highest loading (34%) was achieved at 0.6% NaCl and 10 mg/mL pravastatin for 60 min incubation. At this pravastatin concentration, oxidative stress markers were similar to those seen in controls, and fragility and hematological parameters were unaffected in drug-loaded erythrocytes. These results indicate that the loading process and pravastatin concentration had no deleterious effects on the structure of pravastatinloaded erythrocytes, suggesting that they may therefore have a similar life span to normal cells. Pravastatin-loaded erythrocytes may thus provide an effective extended-release-delivery system for pravastatin.

Rheological and Mucoadhesive Characterization of Poly(vinylpyrrolidone) Hydrogels Designed for Nasal Mucosal Drug Delivery Ibrahim

Ibrahim A. Alsarra,Amel Y. Hamed,Steven H. Neau,Fars K. Alanazi 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.4

Poly(vinylpyrrolidone) (PVP) hydrogels were crosslinked by gamma irradiation to add structure and rigidity, and then rheological and mucoadhesive properties were evaluated. The effects of PVP concentration, radiation dose, and additives, such as poly(ethylene glycol) (PEG) and glycerol, on rheological properties were investigated. In an oscillatory analysis, an increase in polymer concentrations increased the storage modulus (G') and the loss modulus (G'') but decreased the loss tangent (tan δ < 1). The relationships between G' or G'' and the frequency levelled off at higher frequencies, which is indicative of polymer chain entanglement and network formation. Each of the 6% PVP hydrogels exhibited plastic flow with rheopectic behavior. PVP concentration, radiation dose, and the presence of PEG or glycerol influenced the rheological and mucoadhesive properties of the hydrogels. However, adding acyclovir to the formulation did not have a profound effect on the rheological behavior of the hydrogels. The results suggest that a 3% PVP hydrogel with 1% PEG crosslinked with 20 kGy is the most appropriate hydrogel. The results demonstrated the successful complementary application of oscillatory and flow rheometry to characterize and develop a hydrogel for mucosal drug administration.

An investigation into adequacy of separation gap to preclude earthquake-induced pounding

Yazan Jaradat,Pejman Sobhi,Harry Far 국제구조공학회 2023 Structural Engineering and Mechanics, An Int'l Jou Vol.86 No.1

Pounding happens when contiguous structures with differing heights vibrate out of line caused by a seismic activity. The situation is aggravated due to the insufficient separation gap between the structures which can lead to the crashing of the buildings or total collapse of an edifice. Countries around the world have compiled building standards to address the pounding issue. One of the strategies recommended is the introduction of the separation gap between structures. AS1170.4-2007 is an Australian standard that requires 1% of the building height as a minimum separation gap between buildings to preclude pounding. This article presents experimental and numerical tests to determine the adequacy of this specification to prevent the occurrence of seismic pounding between steel frame structures under near-field and far-field earthquakes. The results indicated that the recommended minimum separation gap based on the Australian Standard is inaccurate if low-rise structure in a coupled case is utilised under both near and far field earthquakes. The standard is adequate if a tall building is involved but only when a far-field earthquake happens. The research likewise presents results derived by using the ABS and SRSS methods.

Inference in affine shape theory under elliptical models

Francisco J. Caro-Lopera,José A. Díaz-García,Graciela González-Farías 한국통계학회 2014 Journal of the Korean Statistical Society Vol.43 No.1

This paper studies the elliptical statistical affine shape theory under certain particular conditionson the evenness or oddness of the number of landmarks. In such a case, the relateddistributions are polynomials, and the inference is easily performed; as an example, a landmarkdata is studied, and the performance of the polynomial density versus the usual seriesdensity is compared.

Risk Factors for Mortality in Hospitalized Patients with COVID-19: An Overview in a Mexican Population

( Arturo Cortés-tellés ),( Stephanie López-romero ),( Roberto Mancilla-ceballos ),( Diana Lizbeth Ortíz-farías ),( Nelda Núñez-caamal ),( Esperanza Figueroa-hurtado ) 대한결핵 및 호흡기학회 2020 Tuberculosis and Respiratory Diseases Vol.83 No.-

Background: Currently, Mexico ranks third worldwide in mortality due to coronavirus disease pandemic 2019 (COVID-19) and reliable information is scarce, with the available data focused on epidemiological characteristics. This study aimed to identify the risk factors associated with mortality and outcomes in hospitalized Mexican patients with COVID-19. Methods: We prospectively assessed patients admitted to a COVID-19 reference center in southeast Mexico between March 28 and June 30, 2020. Mortality was defined as survivors or non-survivors and univariate and multivariate logistic regression analyses were performed to explore the association of the clinical characteristics and laboratory parameters with mortality. Results: We included 200 patients with a mean age of 55 years, 69% were men and 72% had at least one chronic comorbidity. Eighty-six patients required invasive mechanical ventilation (IMV) with an overall mortality rate of 82.5%. Only 51% of the patients with IMV were admitted to the intensive care unit (ICU), with a survival rate of 27.3%, but only 7.2% for patients without ICU admissions (p=0.014). The multivariate analysis found that a neutrophil-to-lymphocyte ratio ≥9 (odds ratio [OR], 4.64; 95% confidence interval [CI], 2.05-10.53) albumin <3.5 g/dL (OR, 3.76; 95% CI, 1.56-9.07), lactate dehydrogenase (LDH) level ≥725 U/L (OR, 5.45; 95% CI, 2.36-12.57), and IMV (OR, 64.7; 95% CI, 15.20-275.39) were independent risk factors associated with mortality. Conclusion: Neutrophil-to-lymphocyte ratio, LDH, albumin, and IMV were independent risk factors for mortality in Mexican patients with COVID-19. Also, the availability of ICU resources is invaluable for better outcomes in critically ill patients. Our results could provide clinical information for timely decision-making in low-and-middle income countries to overcome the pandemic.

The Effect of Polyurethane Scaffold Surface Treatments on the Adhesion of Chondrocytes Subjected to Interstitial Perfusion Culture

Manuela Teresa Raimondi,Serena Bertoldi,Silvia Caddeo,Silvia Farè,Chiara Arrigoni,Matteo Moretti 한국조직공학과 재생의학회 2016 조직공학과 재생의학 Vol.13 No.4

The purpose of this study was to measure chondrocytes detachment from cellularized constructs cultured in a perfusion bioreactor, and to evaluate the effect of different scaffold coatings on cell adhesion under a fixed flow rate. The scaffolds were polyurethane foams, treated to promote cell attachment and seeded with human chondrocytes. In a preliminary static culture experiment, the scaffolds were imbibed with fetal bovine serum (FBS) and then cultured for 4 weeks. To quantify cell detachment, the number of detached cells from the scaffold treated with FBS was estimated under different interstitial perfusion flow rates and shear stress levels (0.005 mL/min equivalent to 0.05 mPa, 0.023 mL/min equivalent to 0.23 mPa, and 0.045 mL/min equivalent to 0.45 mPa). Finally, groups of scaffolds differently treated (FBS, plasma plus FBS, plasma plus collagen type I) were cultured under a fixed perfusion rate of 0.009 mL/min, equivalent to a shear stress of 0.09 mPa, and the detached cells were counted. Static cultivation showed that cell proliferation increased with time and matrix biosynthesis decreased after the first week of culture. Perfused culture showed that the number of detached cells increased with the perfusion rate on FBS-treated constructs. The plasma-treated/collagen-coated scaffolds showed the highest resistance to cell detachment. To minimize cell detachment, the perfusion rate must be maintained in the order of 0.02 mL/min, giving a shear stress of 0.2 mPa. Our set-up allowed estimating the resistance to cell detachment under interstitial perfusion in a repeatable manner, to test other scaffold coatings and cell types.

Unilateral Cervical Facet Fractures: Relevance of Acute Disc Injury in Conservative Treatment Failure

Totera Juan Ignacio Cirillo,Vargas Gabriel Hernández,Martini Ignacio Farías,Romero Marcos Gimbernat,Bacciarini Alejandro Urzúa,Plaza José Vicente Ballesteros 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.1

Study Design: Case-control study. Purpose: Analyze association between imaging factors related to the failure of conservative treatment in isolated subaxial cervical facet fractures. Overview of Literature: Facet fracture (F1, F2, and F3 AOSpine) may be stable or unstable depending on clinical and imaging variables, which are not well established. As a result, differences in fracture management lead to differences in surgical or conservative indications, and there is no evidence to predict conservative treatment failure. Methods: Patients were categorized into two groups: six patients (16.2%) with conservative treatment failure (defined as the appearance of neurological symptoms, listhesis >3.5 mm, kyphotic deformation >11°, and/or non-union), and 31 patients (83.7%) with successful conservative management (defined as complete consolidation confirmed by computed tomography [CT] at the 6-month follow-up). All participants were fitted with rigid collars of the Miami type, and standardized follow-up was performed until consolidation or failure. CT and magnetic resonance imaging (MRI) was used to examine imaging characteristics. Sagittal balance parameters were assessed using CT, and signs of acute disc injury, prevertebral edema, facet synovitis, and interspinous hyperintense signal were assessed using MRI. Results: Thirty-seven patients were diagnosed with unilateral cervical facet fractures between 2009 and 2020. In this sample, acute disc injury had a significative association to failure of conservative treatment in F2 and F3 AOSpine facet fractures, 100% of the failure group presented with traumatic disc injury compared to 9.7% of the successful group, for the other variables: prevertebral edema, 83.7% vs. 41.9%; facet synovitis, 100% vs. 77.4%; and interspinous hyperintensity, 71.4% vs. 38.7%, respectively. With conservative management, all F1 fractures healed successfully. Conservative treatment failed in 20% of F2 fractures and 50% of F3 fractures, respectively. In terms of cervical sagittal balance parameters, there were no significant differences between groups. Conclusions: Conservative management was successful in all F1 fractures. In F2 and F3 types, there was a significant association between acute disc injury and conservative treatment failure.