Synthesis Of Di-substituted Polyorganophosphazenes And Fabrication Of Their Anticancer Drug Delivery Systems

Polyorganophosphazenes(POPs)are emerging class of hybrid polymers.POPs consist of an inorganic backbone of alternating nitrogen and phosphorous atoms and two organic side groups attached to the phosphorus atom in each repeating unit.Polydichlorophosphazene(PDCP)provides a platform for the synthesis of POPs.Different techniques such as 1H NMR,31P NMR,GPC and FT-IR are used to confirm the synthesis of POPs.Whereas,other techniques such as TGA,DSC,DLS,TEM and SEM are used to confirm the physical and structural characterization of the various drug carriers of POPs.The availability of wide range of side groups,synthetic flexibility,biocompatibility,biodegradability,tunable mechanical and hydrolytic properties make POPs as attractive biomaterials for drug delivery applications.In addition,blending of POPs with other biomedically important polymers provides an opportunity to develop more efficient drug delivery systems.Due to this reason,parallel progress has been made in the synthesis and drug delivery applications of novel POPs.Particularly their different polymeric structural systems as drug carriers(micelles,polymersomes,membranes,films,fibers,gels,sheets,hydrogels,etc.)have been achieved for drug delivery applications.In our research,we have synthesized different POPs for drug delivery applications by using different organic side groups,which are linked to the phosphorous atoms in backbone of POPs.1)Gastric and pancreatic cancers are worldwide serious diseases and their common method of treatment,chemotherapy is often associated with drawbacks of uncontrolled release of drugs and repeated dosage patterns due to lack of suitable drug carriers.Due to structural stability and chemical composition,the POPs-based fibers/microspheres may provide opportunities to get the controlled drug delivery systems.In our work,four different amino acids-based co-substituted polyorganophosphazenes(POPs),poly[(methyl ferulate)(ethyl valinato)pho sphazene](PMFEVP),poly[(methyl ferulate)(ethyl methioninato)phosphazene](PMFEMP),poly[(ethyl salicylate)(ethyl methioninato)phosphazene](PESEMP)and poly[(ethyl salicylate)(ethyl valinato)phosphazene](PESEVP)were synthesized.These synthesized POPs were characterized by 1H NMR,31P NMR and GPC.After that,their blends were prepared with two commonly used biocompatible polymers,poly(methyl methacrylate)(PMMA)and poly(lactic-co-glycolic acid)(PLGA)to obtain their fibers and microspheres for controlled release of anticancer drugs.Individually two different anticancer drugs "camptothecin" and "aspirin" were loaded in fibers and microspheres,respectively.Their in vitro drug release studies were carried out at body temperature(37?).The microspheres exhibited slow and sustained drug release rate even for a longer time as compared to fibers.Overall,higher drug release rate was observed in acidic medium(pH 5.6)than normal physiological medium(pH 7.4).It is expected that these developed drug delivery systems could be suitable candidates for controlled release of anticancer drugs to cure pancreatic and gastric cancer.2)Cancer cells have reductive and acidic environments as compared to the normal body cells.Development of reductive/acidic responsive polymersomes will play an important role in cancer therapy to trigger the release of the loaded drug.In our work,we synthesized three different reductive/acidic dual responsive polymers,poly[(mPEG-SS-amino)(N,N-diisopropylethylenediamino)phosphazenes](PPDPs)in different mole ratio of side groups.These PPDPs were characterized by 1H NMR,31P NMR,FT-IR and GPC.After that,the PPDPs were allowed to self-assemble into drug-loaded polymersomes.The hydrophilic anticancer drug doxorubicin hydrochloride(DOX-HC1)and hydrophobic drug doxorubicin(DOX)were used.These PPDPs-based drug-loaded polymersomes showed reductive/acidic stimuli responsive release of anticancer drugs.Moreover,these polymersomes also exhibited suitable hydrodynamic diameters,which may facilitate the long time circulation in bloodstream due to avoiding renal clearance and close contact to the tumor cells in vascular sections due to enhanced permeability and retention effect.These developed PPDPs-based reductive/acidic dual responsive polymersomes may provide an effective platform for anticancer drugs delivery.3)Drug delivery studies against different diseases are very important and particularly the development of safe drug carriers is cardinal in cancer therapy,which can target the cancer cells and release the loaded drug on-demand.In our research,we synthesized three different biodegradable polymers,poly[(ethyl aminobezoate)(ethyl glycinato)phosphazenes](PABGPs)in different mole ratio of side groups.These PABGPs were characterized by 1H NMR,31P NMR,FT-IR and GPC.The PABGPs were fabricated into drug loaded nanoparticles in aqueous medium.Hydrophobic anticancer drug(camptothecin,CPT)was used.These drug loaded nanoparticles showed higher release rate of anticancer drug in acidic medium(pH 5.6)as compared to normal physiological medium(pH 7.4)at body temperature(37?).These PABGPs-based nanoparticles may find their application as drug carriers for cancer therapy.