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Synthesis and Evaluation of Substituted Poly(organophosphazenes) as a Novel Nanocarrier System for Combined Antimalarial Therapy of Primaquine and Dihydroartemisinin



The synthesis and evaluation of novel biodegradable poly(organophosphazenes) (36) namely poly[bis-(2-propoxy)]phosphazene (3) poly[bis(4-acetamidophenoxy)]phosphazene (4)poly[bis(4-formylphenoxy)]phosphazene (5) poly[bis(4-ethoxycarbonylanilino)]phosphazene (6) bearing various hydrophilic and hydrophobic side groups for their application as nonocarrier system for antimalarial drug delivery is described.


The characterization of polymers was carried out by IR, 1H-NMR and 31P-NMR. The molecular weights of these novel polyphosphazenes were determined using size exclusion chromatography with a Waters 515 HPLC Pump and a Waters 2414 refractive index detector. The degradation behavior was studied by 200 mg pellets of polymers in phosphate buffers pH 5.5, 6.8 and 7.4 at 37°C. The degradation process was monitored by changes of mass as function of time and surface morphology of polymer pellets. The developed combined drugs nanoparticles formulations were evaluated for antimalarial potential in P. berghei infected mice.


These polymers exhibited hydrolytic degradability, which can afford applications to a variety of drug delivery systems. On the basis of these results, the synthesized polymers were employed as nanocarriers for targeted drug delivery of primaquine and dihydroartemisinin. The promising in vitro release of both the drugs from nanoparticles formulations provided an alternative therapeutic combination therapy regimen for the treatment of drug resistant malaria. The nanoparticles formulations tested in resistant strain of P. berghei infected mice showed 100% antimalarial activity.


The developed nanocarrier system provides an alternative combination regimen for the treatment of resistant malaria.

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Scheme I
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Fig. 12



Proton nuclear magnetic resonance


Phosphorus nuclear magnetic resonance


Alkaline phosphatase


Analysis of variance


Committee for the purpose of control and supervision on experiments on animals


Deuterated water




Dimethyl sulphoxide


Differential scanning calorimetry


Ethylene diamine tetraacetic acid


Entrapment efficiency


Enzyme linked immuno sorbent assay


High performance liquid chromatography


Institutional animal ethical committee




Mega hertz


Mean survival time

Mw :

Molecular weight


National institute of malaria research, New Delhi, India






Phosphate buffer saline




parts per million




Red blood cells


Scanning electron microscopy


Serum glutamic oxaloacetic transaminase


Serum glutamic pyruvate transaminase


Transmission electron microscopy

Tg :

Glass transition temperature


Thermogravimetric analysis








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The authors acknowledge the financial support received from Life Science Research Board (LSRB) of Defense Research and Development Organization (DRDO), New Delhi (India) DL/81/48222/LSRB-232/SH & DD/2011. We are also thankful to Sh. Parveen Garg, Chairman, I.S.F. College of Pharmacy, Moga (Punjab) (India) for providing the necessary facilities to carry out the research work. We also acknowledge Punjab Technical University, Jalandhar (Punjab) (India) for providing necessary facilities for research work.

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Correspondence to T. R. Bhardwaj.

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Kumar, S., Singh, R.K., Murthy, R.S.R. et al. Synthesis and Evaluation of Substituted Poly(organophosphazenes) as a Novel Nanocarrier System for Combined Antimalarial Therapy of Primaquine and Dihydroartemisinin. Pharm Res 32, 2736–2752 (2015).

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  • biodegradable polyphosphazenes
  • degradation
  • dihydroartemisinin
  • drug-resistant malaria
  • nanoparticles
  • primaquine