title: Synthesis and Evaluation of Substituted Poly(organophosphazenes) as a Novel Nanocarrier System for Combined Antimalarial Therapy of Primaquine and Dihydroartemisinin.
abstract: OBJECTIVE
  The synthesis and evaluation of novel biodegradable poly(organophosphazenes) (3-6) 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.
  
  
  METHODS
  The characterization of polymers was carried out by IR, (1)H-NMR and (31)P-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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The developed nanocarrier system provides an alternative combination regimen for the treatment of resistant malaria.
authors.affiliation: Polymer Chemistry and Technology Research Laboratory, Department of Pharmaceutical Chemistry, Indo-Soviet Friendship (I.S.F) College of Pharmacy, Ferozepur Road, Moga, 142001, Punjab, India, sahil.mehta187@gmail.com.
authors.forename: Sahil
authors.initials: S
authors.lastname: Kumar
authors.forename: Rajesh K
authors.initials: RK
authors.lastname: Singh
authors.forename: R S R
authors.initials: RS
authors.lastname: Murthy
authors.forename: T R
authors.initials: TR
authors.lastname: Bhardwaj
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000737:chemistry; D037621:Artemisinins / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000494:pharmacology*; D016503:Drug Delivery Systems; D004563:Electrochemistry; D004912:Erythrocytes / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology; D051379:Mice; D053758:Nanoparticles; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D010316:Particle Size; D010962:Plasmodium berghei; D011108:Polymers / Q000138:chemical synthesis* / Q000494:pharmacology*; D011319:Primaquine / Q000008:administration & dosage* / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D015996:Survival Rate
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004337:Drug Carriers; D009943:Organophosphorus Compounds; D011108:Polymers; C108974:poly(phosphazene); C039060:artenimol; D011319:Primaquine