Polymer Chemistry and Technology Research Laboratory

Moga, India

Polymer Chemistry and Technology Research Laboratory

Moga, India
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Kumar S.,Polymer Chemistry and Technology Research Laboratory | Kumar S.,Punjab Technical University | Bhardwaj T.R.,Polymer Chemistry and Technology Research Laboratory
Journal of Drug Delivery Science and Technology | Year: 2017

The synthesis, characterization and in vitro degradation studies of controlled molecular weight degradable poly(organophosphazenes) bearing various hydrophilic and hydrophobic side group is reported. The polymerization was carried out by thermal polymerization of cyclic trimer hexachlorocyclotriphosphazene at 260 ± 5 °C for 4–5 h to yield poly(dichlorophosphazene). This polymer backbone was suitably substituted with sodium or potassium salts of alcoholic or phenolic compounds and ethyl 4-aminobenzoate to obtain substituted poly(organophosphazenes). 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. These polymers exhibited hydrolytic degradability, which can afford applications to a variety of drug delivery systems. This study shows that poly(organo)phosphazenes could be a potential novel class of biodegradable polymeric carriers for targeted drug delivery. © 2017 Elsevier B.V.


Sharma R.,Polymer Chemistry and Technology Research Laboratory | Sharma R.,A And G Pharmaceutical, Inc. | Singla N.,Polymer Chemistry and Technology Research Laboratory | Mehta S.,Polymer Chemistry and Technology Research Laboratory | And 4 more authors.
Mini-Reviews in Medicinal Chemistry | Year: 2015

Polymer drug conjugates play an important role in the delivery of drugs. In the polymeric drug conjugates, the bioactive agent is combined covalently with polymer to achieve the efficient delivery of bioactive agents in the required or specific period of time along with the enhancement of permeability and retention time. A large number of biodegradable polymers have been widely used in the area of biomedical science. Among them, polyphosphazene, is a biodegradable polymer having versatile nature because of its two chlorine atoms attached on both sides of phosphorus atom of its polymeric backbone, it can be easily replaced by nucleophilic substitution reaction. A plenty of work has been explored for its biomedical applications such as tissue engineering, vaccine drug delivery, polyphosphazene- anticancer drug conjugates with doxorubicin, paclitaxel, platinum complexes, methotrexate and gemcitabine for the targeted drug delivery etc. This review is focused on the recent advances in the biomedical applications of polyphosphazene-drug conjugates. © 2015 Bentham Science Publishers.


Kumar S.,Polymer Chemistry and Technology Research Laboratory | Kumar S.,Punjab Technical University | Sharma R.,Polymer Chemistry and Technology Research Laboratory | Murthy R.S.R.,Polymer Chemistry and Technology Research Laboratory | And 2 more authors.
European Journal of Pharmaceutical Sciences | Year: 2015

Various polymer drug conjugates (13-16) such as primaquine and dihydroartemisinin conjugated 2-propoxy substituted polyphosphazenes (13), primaquine and dihydroartemisinin conjugated 4-acetamidophenoxy substituted polyphosphazenes (14), primaquine and dihydroartemisinin conjugated 4-formyl substituted polyphosphazenes (15) and primaquine and dihydroartemisinin conjugated 4-aminoethylbenzoate substituted polyphosphazenes (16) were synthesized using substituted polyphosphazenes as polymer and primaquine and dihydroartemisinin as combination antimalarial pharmacophores and formulated to nanoparticles to achieve novel controlled combined drug delivery approach for radical cure of malaria. The polymeric backbone was suitably substituted to impart different physicochemical properties. The polymer-drug conjugates were characterized by IR, 1H NMR, 31P NMR and their molecular weights were determined by Gel Permeation Chromatography. The thermal properties of the conjugates (13-16) were studied by DSC and TGA. The conjugates (13-16) were then formulated to nanoparticles formulations to increase their uptake by hepatocytes and to achieve targeted drug delivery. The nanoparticle formulations were characterized by Zeta Sizer and their morphology were studied by TEM (Transmission Electron Microscopy) imaging. The nanoparticles formulations exhibited biphasic in vitro drug release profile, the initial burst release followed by a sustained release owing to the non-fickian diffusion during first step release and fickian diffusion during second step release. In vivo antimalarial efficacy was tested using Plasmodium berghei (NK65 resistant strain) infected swiss albino mice at different doses. The combination therapy exhibited promising antimalarial efficacy at lower doses in comparison to the standard drug combination. Further, this combination therapy provided protection over 35 days without any recrudescence, thus proving to be effective against resistant malaria. The study provides an alternative combination regimen found to be effective in the treatment of resistant malaria. © 2014 Elsevier B.V. All rights reserved.


Sharma R.,Polymer Chemistry and Technology Research Laboratory | Sharma R.,Uttarakhand Technical University | Rawal R.K.,Polymer Chemistry and Technology Research Laboratory | Rawal R.K.,University of Georgia | And 2 more authors.
Bioorganic and Medicinal Chemistry | Year: 2014

Colon-specific azo based polyphosphazene-anticancer drug conjugates (11-18) have been synthesized and evaluated by ex-vivo release studies The prepared polyphosphazene drug conjugates (11-18) are stable in acidic (pH = 1.2) buffer which showed that these polymer drug conjugates are protected from acidic environment which is the primary requirement of colon specific targeted drug delivery The ex-vivo release profiles of polyphosphazene drug conjugates (11-18) have been performed in the presence as well as in the absence of rat cecal content The results showed that more than 89% of parent drugs (methotrexate and gemcitabine) are released from polymeric backbone of polyphosphazene drug conjugates (14 and 18) having n-butanol (lipophilic moiety) The in-vitro cytotoxicity assay has also been performed which clearly indicated that these polymeric drug conjugates are active against human colorectal cancer cell lines (HT-29 and COLO 320 DM) The drug release kinetic study demonstrated that Higuchi's equation is found to be best fitted equation which showed that release of drug from polymeric backbone as square root of time dependent process based on non-fickian diffusion Therefore, the synthesized polyphosphazene azo based drug conjugates of methotrexate and gemcitabine are the potential candidates for colon targeted drug delivery system with minimal undesirable side effects © 2014 Elsevier Ltd All rights reserved.


Kumar S.,Polymer Chemistry and Technology Research Laboratory | Kumar S.,Punjab Technical University | Murthy R.S.R.,Polymer Chemistry and Technology Research Laboratory | Bhardwaj T.R.,Polymer Chemistry and Technology Research Laboratory | Bhardwaj T.R.,Panjab University
Pharmaceutical Research | Year: 2015

Purpose: 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, 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.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. © 2015 Springer Science+Business Media New York


PubMed | Punjab Technical University, Polymer Chemistry and Technology Research Laboratory and Panjab University
Type: | Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences | Year: 2016

Various polymer drug conjugates (13-16) such as primaquine and dihydroartemisinin conjugated 2-propoxy substituted polyphosphazenes (13), primaquine and dihydroartemisinin conjugated 4-acetamidophenoxy substituted polyphosphazenes (14), primaquine and dihydroartemisinin conjugated 4-formyl substituted polyphosphazenes (15) and primaquine and dihydroartemisinin conjugated 4-aminoethylbenzoate substituted polyphosphazenes (16) were synthesized using substituted polyphosphazenes as polymer and primaquine and dihydroartemisinin as combination antimalarial pharmacophores and formulated to nanoparticles to achieve novel controlled combined drug delivery approach for radical cure of malaria. The polymeric backbone was suitably substituted to impart different physicochemical properties. The polymer-drug conjugates were characterized by IR, (1)H NMR, (31)P NMR and their molecular weights were determined by Gel Permeation Chromatography. The thermal properties of the conjugates (13-16) were studied by DSC and TGA. The conjugates (13-16) were then formulated to nanoparticles formulations to increase their uptake by hepatocytes and to achieve targeted drug delivery. The nanoparticle formulations were characterized by Zeta Sizer and their morphology were studied by TEM (Transmission Electron Microscopy) imaging. The nanoparticles formulations exhibited biphasic in vitro drug release profile, the initial burst release followed by a sustained release owing to the non-fickian diffusion during first step release and fickian diffusion during second step release. In vivo antimalarial efficacy was tested using Plasmodium berghei (NK65 resistant strain) infected swiss albino mice at different doses. The combination therapy exhibited promising antimalarial efficacy at lower doses in comparison to the standard drug combination. Further, this combination therapy provided protection over 35days without any recrudescence, thus proving to be effective against resistant malaria. The study provides an alternative combination regimen found to be effective in the treatment of resistant malaria.


Paramjot,Nanomedicine Research Laboratory | Khan N.M.,Nanomedicine Research Laboratory | Kapahi H.,Nanomedicine Research Laboratory | Kumar S.,Polymer Chemistry and Technology Research Laboratory | And 3 more authors.
Journal of Drug Targeting | Year: 2015

Polymers have been utilized to deliver the drug to targeted site in controlled manner, achieving the high-therapeutic efficacy. Polymeric drug conjugates having variable ligands as attachments have been proved to be biodegradable, stimuli sensitive and targeted systems. Numerous polymeric drug conjugates having linkers degraded by acidity or intracellular enzymes or sensitive to over expressed groups of diseased organ/tissue have been synthesized during last decade to develop targeted delivery systems. Most of these organs have number of receptors attached with different cells such as Kupffer cells of liver have mannose-binding receptors while hepatocytes have asialoglycoprotein receptors on their surface which mainly bind with the galactose derivatives. Such ligands can be used for achieving high targeting and intracellular delivery of the drug. This review presents detailed aspects of receptors found in different cells of specific organ and ligands with binding efficiency to these specific receptors. This review highlights the need of further studies on organ-specific polymer-drug conjugates by providing detailed account of polymeric conjugates synthesized till date having organ-specific targeting. © 2015 Informa UK Ltd.


Singla N.,Polymer Chemistry and Technology Research Laboratory | Sharma R.,Polymer Chemistry and Technology Research Laboratory | Bhardwaj T.R.,Polymer Chemistry and Technology Research Laboratory
Letters in Drug Design and Discovery | Year: 2014

The different substituted polyphosphazene-linked azo prodrug of Methotrexate (9-12) and chitosan-linked azo prodrug of methotrexate (13) were synthesized and characterized by modern analytical techniques such as IR, 1H NMR, 31P NMR and GPC. The in-vitro stability study showed that all polymeric drug conjugates are stable in upper GIT (pH = 1.2) and small intestine (pH = 7.4). In-vitro drug release showed that polyphosphazene-linked azo prodrug of methotrexate (12) has maximum release (88.4%) in the presence of rat cecal content compared to chitosan linked azo prodrug of methotrexate (13). Therefore, the synthesized polyphosphazene linked azo based drug conjugates of methotrexate (9-12) are the potential candidates for colon targeted drug delivery system with minimal undesirable side effects. © 2014 Bentham Science Publishers.


Kumar S.,Polymer Chemistry and Technology Research Laboratory | Singh R.K.,Polymer Chemistry and Technology Research Laboratory | Murthy R.S.,Polymer Chemistry and Technology Research Laboratory | Bhardwaj T.R.,Polymer Chemistry and Technology Research Laboratory
Pharmaceutical research | Year: 2015

PURPOSE: 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.


PubMed | Polymer Chemistry and Technology Research Laboratory
Type: Journal Article | Journal: Pharmaceutical research | Year: 2015

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.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 200mg pellets of polymers in phosphate buffers pH5.5, 6.8 and 7.4 at 37C. 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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