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L-Asparaginase encapsulated intact erythrocytes for treatment of acute lymphoblastic leukemia (ALL)
Kwon, Y.M.,Chung, H.S.,Moon, C.,Yockman, J.,Park, Y.J.,Gitlin, S.D.,David, A.E.,Yang, V.C. Elsevier Science Publishers 2009 Journal of controlled release Vol.139 No.3
As a primary drug for the treatment of acute lymphoblastic leukemia (ALL), encapsulation of L-asparaginase (ASNase) into red blood cells (RBC) has been popular to circumvent immunogenicity from the exogenous protein. Unlike existing methods that perturbs RBC membranes, we introduce a novel method of RBC-incorporation of proteins using the membrane-translocating low molecular weight protamine (LMWP). Confocal study of fluorescence-labeled LMWP-ovalbumin, as a model protein conjugate, has shown significant fluorescence inside RBCs. Surface morphology by scanning electron microscopy of the RBCs loaded with LMWP-ASNase was indistinguishable with normal RBCs. These drug loaded RBCs also closely resembled the profile of the native erythrocytes in terms of osmotic fragility, oxygen dissociation and hematological parameters. The in vivo half-life of enzyme activity after administering 8 units of RBC/LMWP-ASNase in DBA/2 mice was prolonged to 4.5+/-0.5 days whereas that of RBCs loaded with ASNase via a hypotonic method was 2.4+/-0.7 days. Furthermore, the mean survival time of DBA/2 mice bearing mouse lymphoma cell L5178Y was improved by ∼44% compared to the saline control group after treatment with the RBC loaded enzymes. From these data, an innovative, novel method for encapsulating proteins into intact and fully functional erythrocytes was established for potential treatment of ALL.
David, A.E.,Cole, A.J.,Chertok, B.,Park, Y.S.,Yang, V.C. Elsevier Science Publishers 2011 Journal of controlled release Vol.152 No.1
Magnetic nanoparticles (MNP) continue to draw considerable attention as potential diagnostic and therapeutic tools in the fight against cancer. Although many interacting forces present themselves during magnetic targeting of MNP to tumors, most theoretical considerations of this process ignore all except for the magnetic and drag forces. Our validation of a simple in vitro model against in vivo data, and subsequent reproduction of the in vitro results with a theoretical model indicated that these two forces do indeed dominate the magnetic capture of MNP. However, because nanoparticles can be subject to aggregation, and large MNP experience an increased magnetic force, the effects of surface forces on MNP stability cannot be ignored. We accounted for the aggregating surface forces simply by measuring the size of MNP retained from flow by magnetic fields, and utilized this size in the mathematical model. This presumably accounted for all particle-particle interactions, including those between magnetic dipoles. Thus, our ''corrected'' mathematical model provided a reasonable estimate of not only fractional MNP retention, but also predicted the regions of accumulation in a simulated capillary. Furthermore, the model was also utilized to calculate the effects of MNP size and spatial location, relative to the magnet, on targeting of MNPs to tumors. This combination of an in vitro model with a theoretical model could potentially assist with parametric evaluations of magnetic targeting, and enable rapid enhancement and optimization of magnetic targeting methodologies.
The impact of incontinence etiology on artificial urinary sphincter outcomes
Adam R. Miller,Brian J. Linder,Laureano J. Rangel,David Y. Yang,Daniel S. Elliott 대한비뇨의학회 2017 Investigative and Clinical Urology Vol.58 No.4
Purpose: To evaluate the impact of incontinence etiology on artificial urinary sphincter (AUS) device outcomes. Materials and Methods: We identified 925 patients who underwent primary AUS placement from 1983 to 2011. The etiology of incontinence was categorized as radical prostatectomy alone, radical prostatectomy with radiation, benign prostate resection, and those with cryotherapy as a salvage prostate cancer treatment. Hazard regression and competing risk analyses were used to determine the association of the etiology of incontinence with device outcomes. Results: The distribution of the 4 etiologies of incontinence included: 598 patients (64.6%) treated with prostatectomy alone, 206 (22.2%) with prostatectomy and pelvic radiation therapy, 104 (11.2%) with benign prostate resection, and 17 (1.8%) with prior cryotherapy. With a median follow-up of 4.9 years (interquartile range, 1.2–8.8 years), there was significant difference in the cumulative incidence of device infection/urethral erosion events between the four etiologies (p=0.003). On multivariable analysis, prior cryotherapy (reference prostatectomy alone; hazard ratio [HR], 3.44; p=0.01), older age (HR, 1.07; p=0.0009) and history of a transient ischemic attack (HR, 2.57; p=0.04) were associated with an increased risk of device infection or erosion. Notably, pelvic radiation therapy with prostatectomy was not associated with an increased risk of device infection or erosion (reference prostatectomy alone, p=0.30). Conclusions: Compared to prostatectomy alone, prior treatment with salvage cryotherapy for recurrent prostate cancer was associated with an increased risk of AUS infection/erosion, whereas radiation (in addition to prostatectomy) was not.
Choi Nam-Kyong,Shantakumar Sumitra,Kim Mi-Sook,Lee Chang-Hoon,Cheng Wendy Y,Bobbili Priyanka,Yang Bo Ram,Lee Joongyub,Hinds David,Duh Mei Sheng,Korves Caroline,Park Heung-Woo 대한천식알레르기학회 2022 Allergy, Asthma & Immunology Research Vol.14 No.2
Purpose: Although asthma treatment guidelines recommend regular inhaled medication, real-world treatment patterns and outcomes in South Korea have not been examined. We examined real-world treatment patterns and outcomes among patients treated for asthma in South Korea. Methods: This retrospective cohort study utilized data from the South Korean National Health Insurance database (2013–2016). Newly treated patients with asthma aged ≥18 years without history of chronic obstructive pulmonary disease were included. Initial and maintenance medication prescriptions were examined. Treatment discontinuation and switch were described. Asthma exacerbation rates, poor asthma control, and healthcare resource utilization (HRU) were compared between maintenance treatment groups (inhaled versus oral) using adjusted incidence rate ratios (aIRR) and hazard ratios (aHR). Results: Overall, 1,054,707 patients initiated any asthma medication; 37,868 patients initiated inhaled (n = 9,983, 26.4%) or oral (n = 27,885, 73.6%) maintenance medication. More patients initiating inhaled versus oral asthma medication discontinued treatment within 12 months (94.4% vs. 86.3%; P < 0.0001). Patients treated with inhaled and oral medication switched treatment (2.5% and 2.3%; P = 0.4160, respectively). Patients initiating inhaled medication had significantly lower rates of asthma exacerbation (aIRR, 0.52; 95% CI, 0.39–0.69), lack of asthma control (aHR, 0.55; 95% CI, 0.48–0.62; P < 0.0001), all-cause and asthma-related HRU versus oral medication. Conclusions: Despite current asthma guidelines, more patients in South Korea were prescribed oral than inhaled medications, resulting in suboptimal asthma management and increased HRU. This study highlights the need to reduce oral corticosteroid prescriptions for optimized treatment in asthma management.