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An Aptamer–Doxorubicin Physical Conjugate as a Novel Targeted Drug-Delivery Platform
Bagalkot, Vaishali,Farokhzad, Omid C.,Langer, Robert,Jon, Sangyong WILEY-VCH Verlag 2006 Angewandte Chemie Vol.45 No.48
<B>Graphic Abstract</B> <P>Trojan aptamer: A novel strategy for targeted drug delivery to cancer cells was developed through the formation of a physical conjugate (see scheme) between doxorubicin (Dox) and the A10 RNA aptamer that binds to the prostate-specific membrane antigen (PSMA). The aptamer–Dox conjugate could efficiently bind to PSMA-expressing cells, thereby resulting in its uptake and the intracellular release of Dox. <img src='wiley_img/14337851-2006-45-48-ANIE200602251-content.gif' alt='wiley_img/14337851-2006-45-48-ANIE200602251-content'> </P>
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A Combined Chemoimmunotherapy Approach Using a Plasmid−Doxorubicin Complex
Bagalkot, Vaishali,Lee, In-Hyun,Yu, Mi Kyung,Lee, Eunhye,Park, Saeho,Lee, Jae-Hyuk,Jon, Sangyong American Chemical Society 2009 MOLECULAR PHARMACEUTICS Vol.6 No.3
<P>We report a combined chemoimmunotherapy vehicle consisting of plasmid loaded with doxorubicin and evaluate its efficacy in two different tumor models. A stable complex was formed with a 1300:1 ratio of doxorubicin bound to native plasmid via intercalation. Pharmacokinetics of the complex showed much slower clearance from plasma up to 3 h compared to 10 min for free doxorubicin. In mice bearing NCI-H358 xenografts, lower doses of complex (doxorubicin 0.5 mg/kg, plasmid 4 mg/kg) effectively reduced tumor growth compared to high doses (5 mg/kg) of free doxorubicin (68% versus 77%). Similar results were observed in mice bearing 4T1 murine allografts; the complex (doxorubicin 2 mg/kg, plasmid 8 mg/kg) was effective and caused similar reduction of tumor compared to free doxorubicin (4 mg/kg) (47% versus 46%). The complex showed no signs of severe systemic toxicity or cardiotoxicity compared to the free doxorubicin in mice as indicated by body weights and heart tissue histology. Elevated levels of cytokines (IL-12, IL-6, and IFN-gamma) were observed in serum as well as in tumor tissue after intravenous injection of complex when compared to plasmid or doxorubicin alone. This approach simultaneously delivers both chemotherapeutic and immunotherapeutic agents without time delay, improves pharmacokinetics of the free drug, lowers drug toxicity, upregulates a variety of cytokines, and is effective against different tumors.</P>
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Nikhil Bagalkot,Govindarajan Suresh Kumar 한국지질과학협의회 2016 Geosciences Journal Vol.20 No.5
A variable aperture model, instead of a conventional parallel plate model, is utilized to study the transport of radionuclides in a single coupled fracture-matrix system. A fully implicit finite difference model has been developed, which incorporates fracture aperture width variation in the numerical study of two species radionuclide transport. Two distinct geometric profiles namely, sinusoidal and logarithmic have been used to capture the variation of aperture width. The dependence of advection, hydrodynamic dispersion, linear sorption, and matrix diffusion on aperture width is considered in the analysis of radionuclides transport. Two species (parent and daughter) radioactive decay chain is also incorporated. There is a greater retardation of radionuclides in fracture for the variable aperture model than the parallel plate model. Sensitivity analysis on fracture surface sorption coefficient, longitudinal dispersivity, matrix porosity, and matrix diffusion coefficient shows that the conventional parallel plate model overestimate the radionuclide concentration in the fracture when compared to the variable aperture model.
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Effect of random fracture aperture on the transport of colloids in a coupled fracture-matrix system
Nikhil Bagalkot,Govindarajan Suresh Kumar 한국지질과학협의회 2017 Geosciences Journal Vol.21 No.1
A variable aperture model, including the random variation of fracture aperture as against the conventional parallel plate model, has been developed to adequately examine the transport of colloids/suspended particles in a single coupled fracturematrix system. Rather than relying on a complex geostatistical method for an accurate representation of fracture aperture, which requires an enormous field data and resource for its validation, a simple statistical method (linear congruential generator) is implemented in the present article. The random variation of fracture aperture is an honest representation of the unpredictable geometry/ morphology of fracture aperture in comparison with widely applied the conventional parallel plate model or the simple mathematical functions based on fractal theory (self-affine structures). A considerable number of parameters are involved in investigating the extent of penetration of colloids into the rock matrix, which creates complexity and ambiguity in the analysis. To overcome this problem, a single parameter “Maximum Penetration Factor” has been introduced for simple and reliable assessment of diffusion of colloids within the rock matrix. Additionally, a non-dimensional parameter ‘Matrix Mitigation Factor’ has been introduced in the present study, which can provide a means of evaluating the diffusion of suspended particles within the rock matrix when it comes to real time applications like microbial enhanced recovery (MEOR) and chemical enhanced recovery (CEOR) in the petroleum industry (nanoparticles and nanofluids). A semi-implicit finite difference model has been adopted for solving the coupled partial differential equations in the present numerical study. Finally, Neumann and Robinson boundary conditions as a function of time have been applied at the fracture inlet to better represent the field scenario as against the conventional constant source condition (Dirichlet). The model results indicate that there is a difference in concentration between the parallel plate model and random fracture model when it comes to colloidal concentration in the fracture and rock matrix. The variance in concentration is due to the inclusion of variation of the aperture in the variable aperture model, which is absent in the parallel plate model. Additionally, the results suggest that the variable source boundary condition has a significant influence on the transport of colloids in fracture-matrix system. Finally, from the evaluation of the extent of diffusion of colloids into rock matrix, it was concluded that that variable aperture model is associated with more mitigation of colloids compared to the parallel plate model, especially in the case of random fracture.
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( Dipendra Raj Pandeya ),( Bagalkot T ),( Jay Kumar Das ),( Roshan D’souza ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1
Background: Hepatitis B virus (HBV) and hepatitis (HCV) C virus are endemic in India and have an aetiological role in acute hepatitis, 50 - 70%, of which end up with chronic liver disease. The aim of this study was to determine the prevalence of Hepatitis B virus (HBV) and Hepatitis C virus (HCV)and their dual infection among patients admitted in Tertiary care Hospital in Ahmednagar, Maharashtra Methods: This descriptive hospital based study was conducted between August 2010 to July 2011 at Tertiary care Hospital Ahmednagar, Maharashtra. The pathological research laboratory is situated in the hospital premises. All the patients who were admitted in the hospital were included in the study after taking informed consent. Three (3) ml of blood was collected in a syringe without anticoagulant from anticubital vein with all aseptic precaution. Serum was separated and screened for the presence of hepatitis B surface antigen (HBsAg) and Antibodies against Hepatitis C. The tests were performed according to the manufacturer’s instructions provided in the kit. A questionnaire was completed from all positive patients. All the information was entered in a standard form. Results: A total of 2230 patients were enrolled in the study. Out of 2230 patients 1562(70.04%) were male and 668 (29.95%) were female. All patients under went screening for HBV and HCV. Age wise distribution and seropositivity of HBV & HCV infection by age is given in table 2. Hepatitis b and Hepatitis c was present in 61 (02.37%) patients, out of these 61 patients 44 (72.13%) were male and 17 (27.86%) were female. Hepatitis B was present in 46 (02.06%) patients, Hepatitis c was present in 13(0.58%) patients and 02 (0.0089%) patients were positive for both Hepatitis B and Hepatits C. Sex wise seropositivity is given in table no. 1. The overall prevalence of HBV infection within the study period was 2.06%, HCV 0.58% and for HBV & HCV both was 0.089%. Regarding the prediposing factors, past history of surgery 17 (27.86%), Blood transfusion 22 (36.06%), Dental procedure 07 (11.47%), Injection & drug abuse 04 (06.55%), Barbar shaving 02 (03.27%), and No known risk factor 09(14.75%) were found. Conclusions: For the prevention of transmission of HBV and HCV infection, the community awareness regarding vaccination against Hepatitis B and risk factors for spread of HBV & HCV, implementation of population based screening and vaccination for HBV on large scale should be ensured.
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정환정,Tarique Rajasaheb Bagalkot,Hyeon Soo Kim,한연희,김민주,임석태,손명희 대한핵의학회 2020 핵의학 분자영상 Vol.54 No.2
Purpose 2-Deoxy-2-[18F] fluoro-d-glucose positron emission tomography (18F-FDG-PET) is a less-invasive and widely used diagnostic tool for detection of malignant tumors. However, prolonged retention of 18F-FDG in the body increases radiation exposure. This study evaluated the effect of oral administration of milk and ursodeoxycholic acid (UDCA) in terms of reducing radiation exposure by 18F-FDG. Methods 18F-FDG radioactivity was measured using a digital γ counter in the whole body and in various organs of rats after oral administration of milk andmilk plusUDCA (milk + UDCA).Western blotting was performed to measure the expression levels of G6Pase, HK 2, CREB, FoxO1, and PGC-1α in the brain, liver, small intestine, and large intestine to assess the mechanism underlying the reduction in radiation exposure from 18F-FDG by oral administration of milk and UDCA. Results We found a significant reduction in 18F-FDG radioactivity in the whole body and in the brain, liver, and small and large intestines. Expression of G6Pase was significantly increased in the above-mentioned organs in the milk and milk + UDCA groups. Expression of HK 2 was significantly decreased in the brain and small intestine in the milk and milk + UDCA groups. CREB, FoxO1, and PGC-1α expression levels in the brain, liver, and small intestine were increased in the milk and milk + UDCA groups. However, expression of PGC-1α in the large intestine in the milk and milk + UDCA groups was significantly decreased compared with that in the control group. Conclusion The present study demonstrated that administration of milk and UDCA increased G6Pase expression levels and 18FFDG release from the tissue. These results suggest milk and UDCA could be used to reduce radiation exposure from 18F-FDG after image acquisition. The mechanisms underpinning this phenomenon should be explored in a human study.
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( Dipendra Raj Pandeya ),( Bagalkot T ),( Jay Kumar Das ),( Roshan D`souza ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.-
Background: Hepatitis B virus (HBV) and hepatitis (HCV) C virus are endemic in India and have an aetiological role in acute hepatitis, 50 - 70%, of which end up with chronic liver disease. The aim of this study was to determine the prevalence of Hepatitis B virus (HBV) and Hepatitis C virus (HCV)and their dual infection among patients admitted in Tertiary care Hospital in Ahmednagar, Maharashtra Methods: This descriptive hospital based study was conducted between August 2010 to July 2011 at Tertiary care Hospital Ahmednagar, Maharashtra. The pathological research laboratory is situated in the hospital premises. All the patients who were admitted in the hospital were included in the study after taking informed consent. Three (3) ml of blood was collected in a syringe without anticoagulant from anticubital vein with all aseptic precaution. Serum was separated and screened for the presence of hepatitis B surface antigen (HBsAg) and Antibodies against Hepatitis C. The tests were performed according to the manufacturer`s instructions provided in the kit. A questionnaire was completed from all positive patients. All the information was entered in a standard form. Results: A total of 2230 patients were enrolled in the study. Out of 2230 patients 1562(70.04%) were male and 668 (29.95%) were female. All patients under went screening for HBV and HCV. Age wise distribution and seropositivity of HBV & HCV infection by age is given in table 2. Hepatitis b and Hepatitis c was present in 61 (02.37%) patients, out of these 61 patients 44 (72.13%) were male and 17 (27.86%) were female. Hepatitis B was present in 46 (02.06%) patients, Hepatitis c was present in 13(0.58%) patients and 02 (0.0089%) patients were positive for both Hepatitis B and Hepatits C. Sex wise seropositivity is given in table no. 1. The overall prevalence of HBV infection within the study period was 2.06%, HCV 0.58% and for HBV & HCV both was 0.089%. Regarding the prediposing factors, past history of surgery 17 (27.86%), Blood transfusion 22 (36.06%), Dental procedure 07 (11.47%), Injection & drug abuse 04 (06.55%), Barbar shaving 02 (03.27%), and No known risk factor 09(14.75%) were found. Conclusions: For the prevention of transmission of HBV and HCV infection, the community awareness regarding vaccination against Hepatitis B and risk factors for spread of HBV & HCV, implementation of population based screening and vaccination for HBV on large scale should be ensured.
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Hwang, Hyosook,Kim, Hyeon-Soo,Jeong, Hwan-Seok,Rajasaheb, Bagalkot Tarique,Kim, Minjoo,Oh, Phil-Sun,Lim, Seok Tae,Sohn, Myung-Hee,Jeong, Hwan-Jeong Informa Healthcare 2016 DRUG DELIVERY Vol.23 No.9
<P>Background: We investigated the therapeutic effectiveness of PEGylated liposomes loaded with angiogenic peptides for treating hindlimb ischemia.Methods: Rats received a femoral artery occlusion. Red blood cells collected from the animals were labeled with technetium-99m. Limb perfusion gamma imaging was performed. PEGylated liposomes loaded with angiogenic peptides were administered intra-arterially. Technetium-99m red blood cell imaging was repeated 1 week later. The animals were sacrificed the next day. The expression of angiogenic proteins was studied. Later, changes in limb perfusion after intra-arterial infusion versus intra-muscular injection were also compared to determine the therapeutic effectiveness of different administration methods.Results: Femoral artery occlusion dramatically reduced ischemic limb perfusion (by an average of 69%, compared to contralateral limb). This was not different among groups (p>0.05). Liposomes loaded with angiogenic peptides significantly improved ischemic limb perfusion, compared to controls (210% of baseline, versus 100% of baseline in control; p<0.05 versus controls). The enhanced ischemic limb perfusion was accompanied by an increased expression of CD 31 (an average of 1.6-fold increase of controls; p<0.05). The liposomes or peptides treatment alone did not affect ischemic perfusion (liposomes alone: 100% of baseline; peptides alone: 120% of baseline; p>0.05 versus controls, respectively) or the angiogenic response (1.1-fold of controls in liposomes alone; 1.0-fold of controls in peptides alone; p>0.05 versus controls, respectively). Intra-muscular injection induced similar liposomal treatment effects on ischemic limb perfusion (230% of baseline) as those by intra-arterial infusion (210% of baseline; p<0.05 versus intra-muscular).Conclusions: PEGylated liposomes loaded with angiogenic peptides improved ischemic limb perfusion and promoted angiogenic responses. Liposomal angiogenic treatment via intra-arterial infusion resulted in an equally effective therapeutic efficacy compared to that of intra-muscular injection. These results show the therapeutic potential of our liposomal strategy for treating peripheral limb ischemia.</P>
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Co-Delivery of Hydrophobic and Hydrophilic Drugs from Nanoparticle–Aptamer Bioconjugates
Zhang, Liangfang,Radovic-Moreno, Aleksandar F.,Alexis, Frank,Gu, Frank X.,Basto, Pamela A.,Bagalkot, Vaishali,Jon, Sangyong,Langer, Robert S.,Farokhzad, Omid C. WILEY-VCH Verlag 2007 ChemMedChem Vol.2 No.9
<B>Graphic Abstract</B> <P>Herein we report a novel targeted drug delivery system consisting of nanoparticle–aptamer bioconjugates, which can carry both hydrophobic and hydrophilic chemotherapeutic drugs simultaneously, and deliver them selectively in a targeted and temporally distinct manner. This work provides a robust platform for targeted co-delivery of chemotherapeutic agents with the hope of both leveraging the synergistic effects of multiple drugs and also potentially suppressing the likelihood of drug resistance by the treated tissues. <img src='wiley_img/18607179-2007-2-9-CMDC200700121-content.gif' alt='wiley_img/18607179-2007-2-9-CMDC200700121-content'> </P>
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