Design, Synthesis, and Antimycobacterial Property of PEG–bis(INH) Conjugates

Kakkar, Dipti; Tiwari, Anjani Kumar; Chuttani, Krishna; Khanna, Alka; Datta, Anupama; Singh, Harpal; Mishra, Anil K.

doi:10.1111/j.1747-0285.2012.01394.x

Cited by 14 publications

(13 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The labeled formulations, thus obtained, were stored in sterile shielded vials for subsequent studies. The radiolabeling efficiency was determined by ascending instant thin layer chromatography (ITLC) as reported in detail elsewhere [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

Potential carriers of chemotherapeutic drugs: matrix based nanoparticulate polymeric systems

et al. 2014

Self Cite

View full text Add to dashboard Cite

In this work matrix based nanoparticulate polymer systems have been designed using the diacrylate derivative of the well-known biocompatible polymer, poly(ethylene glycol) (PEG). This has been crosslinked using bifunctional (ethyleneglycol dimethacrylate) and tetrafunctional (pentaerythritol tetraacrylate) crosslinkers in varied concentrations (10-90%) to result in a polymeric network. The crosslinked polymers thus obtained were characterized by spectroscopic techniques (NMR and FTIR) and then prepared nanoparticles by the nanoprecipitation technique. Particle size analysis showed sizes of ~150 nm (PDI < 1) (with tetrafunctional crosslinker) and ~300 nm (with bifunctional crosslinker). Both the systems however showed unimodal narrow particle size distributions with negative zeta potential values of -15.6 and -7.3 respectively. Cytotoxicity of these formulations was evaluated by MTT assay showing non-cytotoxic nature of these carrier systems. In vitro drug loading and release studies were carried out using a model chemotherapeutic drug, methotrexate(MTX). These MTX loaded nanoformulations have also been evaluated biologically with the help of in vivo studies using radiolabeling techniques (with 99mTc radionuclide). The blood kinetics profile of the formulations was studied on New Zealand Albino rabbits while the biodistribution studies were performed on balb/c mice (with EAT tumours), which revealed a hepatobiliary mode of elimination. These preliminary studies clearly demonstrated the ability of these multifunctional crosslinkers to result in tight nanosized networks with biocompatible polymers such as PEG and their potential to carry chemotherapeutic drugs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12645-014-0003-9) contains supplementary material, which is available to authorized users.

show abstract

Section: Methodsmentioning

confidence: 99%

Potential carriers of chemotherapeutic drugs: matrix based nanoparticulate polymeric systems

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…To evaluate the stability, specificity, and biodistribution profile of MBIP‐Cl and MBIP‐Br compounds, they were labeled with 99m Tc using procedure from literature with slight modifications (Kakkar et al, ; Srivastava et al, 2013). Briefly, 100 μL of sterile sodium pertechnetate (approximately 74–110 MBq of 99m TcO 4 ) was reduced with 50 μL of stannous chloride solution (1 × 10 −2 M in 10% glacial acetic acid) and pH was adjusted to 6.5 using 0.5 M sodium bicarbonate.…”

Section: Methodsmentioning

confidence: 99%

Modified benzoxazolone (ABO‐AA) based single photon emission computed tomography (SPECT) probes for 18 kDa translocator protein

Srivastava

Kakkar

Kumar

et al. 2019

Drug Development Research

Self Cite

View full text Add to dashboard Cite

Acetamidobenzoxazolone (ABO) has been modified to ABO‐AA, 2‐(2‐(5‐bromo/chloro benzoxazolone)acetamide)‐3‐(1H‐indol‐3‐yl)propionate to improve pharmacokinetics and lipophilicity (log p = 2.04). The final compound was synthesized in better yield and in fewer steps than previously reported MBIP‐Br (70% vs. 62%). Computational docking confirmed binding of MBIP‐Cl with translocator protein (TSPO) as well as with mutant TSPO (−8.99 for PDB: 4RYQ and −9.30 for PDB: 4UC1, respectively). Ex‐vivo biodistribution and scintigraphy showed that 99mTc‐MBIP‐Cl is better than 99mTc‐MBIP‐Br in terms of uptake in TSPO‐rich organs and release kinetics 0–120 min postinjection. At 15 min, uptake was 2.75‐fold (12.91%ID/g vs. 4.69%ID/g) in lung and seven‐fold (5.16%ID/g vs. 0.72%ID/g) in heart for 99mTc‐MBIP‐Cl compared to that of 99mTc‐MBIP‐Br which gives warrant to utilize this single photon emission computed tomography agent in higher animals.

show abstract

“…Imaging of bacterial infections is by far the most developed area of infection imaging. Multiple antibiotics with a variety of mechanisms of action such as ciproflaxicin (7,8) and nitrofuryl thiosemicarbazone (7), fluoroquinolone (9), isoniazid (10), ofloxacin (11,12), cephalosporin (13), clindamycin (14), doxycycline (15), ceftizoxime (16,17), cefotaxime (18), tinidazole (19), sulfadiazine (20), tazobactam (21) and metronidazole (22) were radiolabeled with 99m Tc to enable SPECT imaging in the pre-clinical models of infection. The majority of the authors employed Sn(+2) salts as the reducing agents for 99m Tc which produced [ 99m Tc-O](3+) core, while in several publications 99m Tc carbonyl or [ 99m Tc-N](2+) cores were utilized (7,8,11).…”

Section: Imaging Bacterial Infections With Radiolabeled Antibiotics S...mentioning

confidence: 99%

Highlights of the Latest Developments in Radiopharmaceuticals for Infection Imaging and Future Perspectives

Dadachova

Rangel

2022

Front. Med.

View full text Add to dashboard Cite

COVID-19 pandemic has heightened the interest toward diagnosis and treatment of infectious diseases. Nuclear medicine with its powerful scintigraphic, single photon emission computer tomography (SPECT) and positron emission tomography (PET) imaging modalities has always played an important role in diagnosis of infections and distinguishing them from the sterile inflammation. In addition to the clinically available radiopharmaceuticals there has been a decades-long effort to develop more specific imaging agents with some examples being radiolabeled antibiotics and antimicrobial peptides for bacterial imaging, radiolabeled anti-fungals for fungal infections imaging, radiolabeled pathogen-specific antibodies and molecular engineered constructs. In this opinion piece, we would like to discuss some examples of the work published in the last decade on developing nuclear imaging agents for bacterial, fungal, and viral infections in order to generate more interest among nuclear medicine community toward conducting clinical trials of these novel probes, as well as toward developing novel radiotracers for imaging infections.

show abstract

Design, Synthesis, and Antimycobacterial Property of PEG–bis(INH) Conjugates

Cited by 14 publications

References 21 publications

Potential carriers of chemotherapeutic drugs: matrix based nanoparticulate polymeric systems

Potential carriers of chemotherapeutic drugs: matrix based nanoparticulate polymeric systems

Modified benzoxazolone (ABO‐AA) based single photon emission computed tomography (SPECT) probes for 18 kDa translocator protein

Highlights of the Latest Developments in Radiopharmaceuticals for Infection Imaging and Future Perspectives

Contact Info

Product

Resources

About