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Research


In the area of leishmaniasis major emphasis has been given development of Amphotericin B bearing formulations i.e. lipo-polymerosome, which was found to have low toxicity that showed synergistic efficacy in case of leishmaniasis and further explored targeting potential of Lectin functionalized lipo-polymerosome bearing AmB and found that it has improved pharmacokinetic and pharmacodynamic profile than commercial formulation Fungizone (Bioconjugate Chem. 25 (6), pp 1091–1102 (2014).

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We have also developed oil templated nanocapsules bearing doxorubicin for macrophage targeting through Phosphatidylserine ligand and established that the ligand can provide a new insight for efficient drug delivery to specialized macrophages through “eat me” signal (J. Antimicrob. Chemother. 2012; IF 5.068). The chemotherapeutic potential of alginate coated nanocapsule loaded with doxorubicin was also explored against visceral leishmaniasis in comparison with nano-emulsions containing doxorubicin [Br. J Pharmacol 2014; IF 4.84; Biomacromolecules 13;16(4):1073-87 (2015)].

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We have also observed synergistic enhancement of parasiticidal activity of amphotericin B using copaiba oil in nano-emulsified carrier for oral delivery: an approach for non-toxic chemotherapy.

The in vitro antileishmanial activity of CopNEC-AmB was significantly higher than that of the free drug as Cop synergistically enhanced the antileishmanial effect of AmB by causing drastic changes in the morphology of Leishmania parasite and rupturing its plasma membrane. The CopNEC-AmB showed significantly less haemolytic toxicity and cytotoxicity and did not change the histopathology of kidney tissues as compared with AmB alone. We have also identified that sulfated derivatives of a common sugar (4-SO4GalNAc) could be used as a high-performance targeting ligands to target tissue-resident macrophages especially Leishmania-infected macrophages, suggesting an alternative strategy for the treatment of leishmaniasis.

In the area of osteoporosis we have developed Layer-by-layer technology bearing kaempferol which has impacted on product development by enhancing bioavailability of kaempferol by an order of magnitude with and enhanced osteogenic efficacy. Single oral dose of kaempferol loaded LbL nanomatrix formulation increased bioavailability significantly compared to unformulated kaempferol. Three months of formulated kaempferol administration to osteopenic rats increased plasma and bone marrow Kaempferol levels by 2.8- and 1.75-fold, respectively, compared to free Kaempferol

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Nanomedicine 8(5) 757-771(2013); Eur. J. Pharm. Biopharm. 82 (2012) 508-517

Formulated Kaempferol increased bone marrow osteoprogenitor cells, osteogenic genes in femur, bone formation rate, and improved trabecular micro-architecture. Withdrawal of Formulated kaempferol-in OVx rats resulted in the maintenance of bone micro-architecture up to 30 days, whereas micro-architectural deterioration was readily observed in OVx rats treated with unformulated kaempferol-within 15 days of withdrawal. (Nanomedicine 2013; IF 5.824 and Eur. J. Pharm. Biopharm 2012; IF 4.245. Also granted US, European, Australia Patents.

In the area of Malaria we have developed novel combination kit bearing arteether and sulfadoxine for the treatment of P.falciparum Malaria. In this study, the nano-formulation showed 100% curative effect with nearly 1/4th of curative dose of α/β-arteether in combination of 1/32th of SP curative dose (1983/DEL/2014).

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These formulations have been found to be highly effective against Plasmodium yoelii nigeriensis infected swiss mice even at the lower dose of 12.5 mg/kg x5 days. Overall the developed formulations are safe and provide a non-toxic platform for further clinical studies and can be used in artemisinin-based combination therapies (ACTs).

Recently we have developed paclitaxel nanocrystals with improved delivery. Nanocrystals resulted in much enhanced absorption with 12.6 fold improvement in relative bioavailability to that of TaxolTM. Concomitantly efficacy data in B16 F10 murine melanoma model also showed significant reduction in tumor growth with NCs compared to TaxolTM and control

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Based on the results it can be suggested that NCs with functional stabilizers can be promising approach for oral delivery of anticancer drugs which are P-gp substrates (Acta Biomaterialia 2015).

Selected Publications

1. Ashwni Verma, Shweta Sharma, Pramod Kumar Gupta, Awadhesh Singh, B Venkatesh Teja, Pankaj Dwivedi, Girish Kumar Gupta, Ritu Trivedi, Prabhat Ranjan Mishra Acta biomaterialia 31:288-300 (2016). (I.F. 6.03)

2. Naresh Mittapelly, Ramakrishna Rachumallu, Gitu Pandey, Shweta sharma, Abhishek Arya, Rabi Shanker Bhatta, Prabhat Ranjan Mishra Investigation of salt formation between memantine and pamoic acid: Its exploitation in nanocrystalline form as long acting injection Eur. J. Pharm. Biopharm. 101 (2016) 62–71. (I.F. 3.38)

3. Priyanka Kushwaha, Vikram Khedgikar, Deepika Sharma, Tony Yuen, Jyoti Gautam, Naseer Ahmad, Anirudha Karvande, Prabhat R. Mishra, Prabodh K. Trivedi, Li Sun, Sanjay K. Bhadada, Mone Zaidi, Ritu Trivedi, MicroRNA-874-3p Exerts Skeletal Anabolic Effects Epigenetically During Weaning by Suppressing Hdac1 J. Biol. Chem. DOI: 10.1074/jbc.M115.687152 (I.F 4.57)

4. S Sharma, A Verma, G Pandey, N Mittapelly, PR Mishra Investigating the role of Pluronic-g-Cationic polyelectrolyte as functional stabilizer for nanocrystals: Impact on Paclitaxel oral bioavailability and tumor growth Acta biomaterialia 26, 169-183 (2015) (I.F. 6.03).

5. P Tripathi, P Dwivedi, R Khatik, AK Jaiswal, A Dube, P Shukla, PR Mishra Development of 4-sulfated N-acetyl galactosamine anchored chitosan nanoparticles: A dual strategy for effective management of Leishmaniasis Colloids and Surfaces B: Biointerfaces 136, 150-159 (2015) . (I.F 4.287)

6. Shweta Sharma, B Venkatesh Teja, Gitu Pandey, Naresh Mittapelly, Ritu Trivedi, PR Mishra An Insight into functionalized Calcium based Inorganic Nanomaterials in Biomedicine: Trends and Transitions Colloids and Surfaces B: Biointerfaces 133, 120–139 (2015) (I.F 4.287)

7. Gupta PK, Jaiswal AK, Asthana S, Teja B V, Shukla P, Shukla M, Sagar N, Dube A, Rath SK, Mishra PR Synergistic enhancement of parasiticidal activity of amphotericin B using copaiba oil in nanoemulsified carrier for oral delivery: an approach for non-toxic chemotherapy. Br J Pharmacol. 72(14):3596-610. (2015) doi: 10.1111/bph.13149. (I.F. 4.99)

8. Pramod Kumar Gupta, Anil K Jaiswal, Shalini Asthana, Anuradha Dube, Prabhat Ranjan Mishra Antigen presenting cells targeting and stimulation potential of lipoteichoic acid functionalized lipo-polymerosome: A chemo-immunotherapeutic approach against intracellular infectious disease. Biomacromolecules 13;16(4):1073-87 (2015); DOI:10.1021/bm5015156 (I.F. 5.79)

9. Keerti Jain, Ashwni Kumar Verma, P R Mishra, N K Jain Surface engineered dendrimeric nanoconjugates for macrophage targeted delivery of Amphotericin B: Formulation Development, In Vitro and In Vivo Evaluation Antimicrobial Agents and Chemotherapy 59(5):2479-87 (2015); DOI: 10.1128/AAC.04213-14 (I.F. 4.57)

10. Keerti Jain, A.K. Verma, P.R. Mishra, N.K. Jain Characterization and evaluation of amphotericin B loaded MDP conjugated poly(propylene imine) dendrimers. Nanomedicine: Nanotechnology, Biology, and Medicine, 11(3),705-71 (2015). (I.F. 5.98)

11. Pramod K Gupta, Anil K Jaiswal, Shalini Asthana, Ashwni Verma, Vivek Kumar, Prashant Shukla, Pankaj Dwivedi, Anuradha Dube, Prabhat R Mishra Self Assembled Ionically Sodium Alginate Cross-Linked Amphotericin B Encapsulated Glycol Chitosan Stearate Nanoparticles: Applicability in Better Chemotherapy and Non-Toxic Delivery in Visceral Leishmaniasis. Pharm Res DOI 10.1007/s1 1095-014-1571-4, 32, (5) 1727-1740 (2015). (I.F. 3.952)

12. Atul Goel, Ashutosh Sharma, Manoj Kathuria, Arindam Bhattacharjee, Ashwni Verma, Prabhat R Mishra, Aamir Nazir, Kalyan Mitra New Fluoranthene FLUN-550 as a Fluorescent Probe for Selective Staining and Quantification of Intracellular Lipid Droplets Organic Letters 16 (3), 756–759 (2014). (I.F.6.324)

13. NK Mehra, AK Verma, PR Mishra, NK Jain The cancer targeting potential of d-α-tocopheryl polyethylene glycol 1000 succinate tethered multi walled carbon nanotubes Biomaterials 35 (15), 4573-4588 (2014). (I.F. 8.312)

14. R Khatik, P Dwivedi, P Khare, S Kansal, A Dube, PR Mishra, AK Dwivedi Development of targeted 1, 2-diacyl-sn-glycero-3-phospho-l-serine-coated gelatin nanoparticles loaded with amphotericin B for improved in vitro and in vivo effect in leishmaniasis Exp. Opin. Drug Deliv. 11(5):633-46. (2014) (doi:10.1517/17425247.2014.889678). (I.F 4.12)

15. L Al Shaal, PR Mishra, RH Müller, CM Keck Nanosuspensions of hesperetin: preparation and characterization Pharmazie 69 (3) 173-182 (2014). (I.F. 1.5)

16. Pramod K Gupta, Anil K Jaiswal, Vivek Kumar, Ashwni Verma, Pankaj Dwivedi, Anuradha Dube, Prabhat R Mishra Covalent functionalized Self-assembled Lipo-polymerosome bearing Amphotericin B for better management of leishmaniasis and its toxicity evaluation Mol. Pharm. 11 (3), 951–963 (2014). (I.F.4.787)

17. Vikas Jain, Prashant Shukla, R. Pal and Prabhat Ranjan Mishra Cationic nanoemulsions bearing ciprofloxacin surf-plexes enhances its therapeutic efficacy in conditions of E. coli induced peritonitis and sepsis Pharm Res. 31 (10), 2630-2642 (2014) DOI 10.1007/s1 1095-014--1360-0. (I.F. 3.952)

18. Pankaj Dwivedi, Renuka Khatik, Kiran Khandelwal, Isha Taneja, Kanumuri Siva Rama Raju, Sarvesh Kumar Paliwal, Anil Kumar Dwivedi, Prabhat Ranjan Mishra Pharmacokinetics study of arteether loaded solid lipid nanoparticles: An improved oral bioavailability in rats. Int. J. Pharm. 466 (1), 321-327 (2014). (IF 3.785)

19. S Kansal, R Tandon, A Verma, P Misra, AK Choudhary, R Verma, PRP Verma, A Dube, PR Mishra Coating doxorubicin loaded nanocapsule with alginate enhances therapeutic efficacy against Leishmania in hamsters by inducing Th1 type immune responses Br. J. Pharmacol. 171(17):4038-50. DOI: 10.1111/bph.12754 (2014). (I.F. 4.99)

20. Pramod K. Gupta , Shalini Asthana , Anil K. Jaiswal , Vivek Kumar , Ashwni Verma , Prashant Shukla , Pankaj Dwivedi , Anuradha Dube , and Prabhat R. Mishra Exploitation of Lectinized Lipo-polymerosome bearing Amphotericin B to Target Macrophages for Effective Management of Visceral Leishmaniasis Bioconjugate Chem. 25 (6), pp 1091–1102 (2014) (I.F. 4.7)

21. Prashant Shukla, Vineet Mathur, Amit Kumar, Vikram Khedgikar, B. Venkatesh Teja, Dharmendra Chaudhary, Priyanka Kushwaha, Himangsu K. Bora, Rituraj Konwar, Ritu Trivedi, and Prabhat Ranjan Mishra Nanoemulsion Based Concomitant Delivery of Curcumin and Etoposide: Impact on Cross Talk Between Prostate Cancer Cells and Osteoblast During Metastasis J. Biomed. Nanotechnol. 10 (11) 3381-3391, (2014). (IF 5.39)

22. Prashant Shukla, G. Madhava Rao, Gitu Pandey, Shweta Sharma, Naresh Mittapelly, Ranjita Shegokar, Prabhat Ranjan Mishra Therapeutic Intervention of Sepsis: Current and Anticipated Pharmacological Agents Br. J. Pharmacol. (2014) 171, 5011-5031 (2014). (I.F. 4.99)

23. Prashant Shukla, Pankaj Dwivedi, Pramod Kumar Gupta, Prabhat Ranjan Mishra Optimization of novel tocopheryl acetate nanoemulsions for parenteral delivery of curcumin for therapeutic intervention of sepsis Exp. Opin. Drug Deliv. 11(11):1697-712 (2014). (I.F. 4.12).

24. Prashant Shukla, Ajeet Kumar Verma, Pankaj Dwivedi, Arti Yadav, Pramod Kumar Gupta, Srikanta Kumar Rath, and Prabhat Ranjan Mishra Moxifloxacin-Loaded Nanoemulsions Having Tocopheryl Succinate as the Integral Component Improves Pharmacokinetics and Enhances Survival in E. coli-Induced Complicated Intra-Abdominal Infection Mol. Pharm, 11 (12), 4314–4326 (2014). (I.F.4.787)

25. P Kushwaha ,V Khedgikar, J Gautam,  P Dixit, R Chillara , A Verma, R Thakur D P Mishra, D Singh , R Maurya , N Chattopadhyay , P R Mishra , R Trivedi , A novel therapeutic approach with Caviunin-based isoflavonoid that en routes bone marrow cells to bone formation via BMP2/Wnt-β-catenin signaling Cell Death & Disease 09/2014; 5:e1422. DOI:10.1038/cddis.2014.350 , (I.F 5.01)

26. Pankaj Dwivedi, Renuka Khatik, Kiran Khandelwal, Richa Srivastava, Isha Taneja, Kanumuri Siva Rama Raju, Hemlata Dwivedi, Prashant Shukla, Pramod Gupta, Sarika Singh, Renu Tripathi, Sarvesh Kumar Paliwal, Wahajuddin, Anil Kumar Dwivedi and Prabhat Ranjan Mishra Self-nanoemulsifying drug delivery systems (SNEDDS) for oral delivery of arteether: pharmacokinetics, toxicity and antimalarial activity in mice RSC Adv., 2014,4, 64905-64918 (I.F. 3.708)

27. Girish K Gupta, Avinash Kumar, Vikram Khedgikar, Priyanka Kushwaha, Jyoti Gautam, Geet K Nagar, Varsha Gupta, Ashwini Verma, Anil Kumar Dwivedi, Amit Misra, Ritu Trivedi and Prabhat Ranjan Mishra Enhancement of osteogenic efficacy of kaempferol through engineered layer-by-layer matrix: A study in ovariectomized rats. Nanomedicine 8(5) 757-771(2013). (IF 5.33)

28. Shaswat Kansal, Rati Tandon, Priya Ranjan Prasad Verma, Anuradha Dube and Prabhat Ranjan Mishra, Development of Doxorubicin Loaded Novel Core Shell Structured Nanocapsules for the intervention of Visceral Leishmaniasis J. Microencapsul. 30(5):441-50 (2013) .doi-10.3109/02652048.2012.752532 (I.F 1.585)

29. Khedgikar V, Kushwaha P, Gautam J, Verma A Changkija B, Kumar A, Sharma S, Nagar GK, Singh D, Trivedi PK, Sangwan N S, Mishra PR, Trivedi R. Withaferin A: a proteasomal inhibitor promotes healing after injury and exerts bone anabolic effect. Cell Death and Dis. 4, e778; doi:10.1038/cddis.2013.294 (2013) (IF 6.044)

30. D. Singodia, A. Verma, R.K. Verma, P. R. Mishra Investigations on Alternate Approach to Target Mannose Receptors on Macrophages using 4-Sulfated N-Acetyl Galactosamine more Efficiently as Compared to Mannose Decorated Liposomes : An Application in Drug Delivery, Nanomedicine, Nanotechnology, Biology and Medicine 8 (4) 468-477 (2012) (I.F. 6.67).

31. Vikas Jain, Nitin K. Swarnakar, Prabhat R. Mishra, Ashwni Verma, Ankur Kaul, Anil K. Mishra, Narendra K. Jain Paclitaxel loaded PEGylated gleceryl monooleate based nanoparticulate carriers in chemotherapy Biomaterials 33(29): 7206-20 (2012) (I.F. 8.312).

32. Shaswat Kansal, Rati Tandon, Pankaj Dwivedi, Pragya Misra, P.R.P Verma, Anuradha Dube and Prabhat Ranjan Mishra Development of oil templated nanocapsules bearing doxorubicin for macrophage targeting through Phosphatidylserine ligand: A system for intervention in Visceral Leishmaniasis J. Antimicrob. Chemother. 67 (11), 2650-2660 (2012) doi:10.1093/jac/dks286 (I.F. 5.068).

33. Avinash Kumar, Girish K Gupta , Vikram Khedgikar, Jyoti Gautam, Priyanka Kushwaha, Bendangla Changkija, Geet K Nagar, Varsha Gupta, Ashwni Verma, Anil Kumar Dwivedi, Naibedya Chattopadhyay , Prabhat R Mishra, Ritu Trivedi. In-vivo efficacy studies of layer-by-layer nano-matrix bearing kaempferol for the conditions of osteoporosis: A study in ovariectomized rat model. Eur. J. Pharm. Biopharm. 82 (2012) 508-517 (I.F. 4.268).

34. Pankaj Dwivedi, Shaswat Kansal, Monika Sharma, Rahul Shukla, Ashwini Verma, Prashant Shukla, Priyanka Tripathi, Pramod Gupta, Deepika Saini, Kiran Khandelwal, Rahul Verma, Anil Kumar Dwivedi and Prabhat Ranjan Mishra Exploiting 4-sulphate N-acetyl galactosamine decorated gelatin nanoparticles for effective targeting to professional phagocytes in vitro and in vivo. J. Drug Targeting 20, (10) 883–896 (2012). (I.F. 2.741)

Patents

Granted

1. PR Mishra, Ritu Trivedi, GK Gupta, A Kumar, V Gupta, SK Rath, K Srivastava, N Chattopadhyay A.K. Dwivedi Controlled Release Micro-Capsule for osteogenic action US Patent (2013) 8,496,964.

2. PR Mishra, Ritu Trivedi, GK Gupta, A Kumar, V Gupta, SK Rath, K Srivastava, N Chattopadhyay A.K.Dwivedi Controlled Release Micro-Capsule for osteogenic action EP Patent 2400957 B1 (2013).

3. PR Mishra, Ritu Trivedi, GK Gupta, A Kumar, V Gupta, SK Rath, K Srivastava, N Chattopadhyay A.K.Dwivedi Controlled Release Micro-Capsule for osteogenic action AU Patent 2010/217238 B2 (2013)

4. P.R Mishra, Vure Prasad, A.K. Dwivedi and S Singh “Composition and methods of nonionic surfactant based vesicular formulation for improved delivery of cyclosporine Indian Patent (2013) 258311.


Patents filed

1. Trivedi Dr. Ritu, Mishra Dr. Prabhat R, Sangwan Dr. Neelam S Trivedi Dr. Prabodh Singh Dr. Divya, Sangwan Dr. Rajender S, Kushwaha Priyanka, Khedgikar Vikram Adhikary Sulekha, Choudhary Dharmendra, Swarup Jyoti, Kumar Avinash Karvande Anirudha, Verma Ashwni, Sharma Shweta, Proteasomal inhibitors useful for osteogenic activity and pharmaceutical composition thereof 2145/DEL 2013 17.07.2013

2. Trivedi Dr. Ritu, Mishra Dr. Prabhat R, Sangwan Dr. Neelam S Trivedi Dr. Prabodh Singh Dr. Divya, Sangwan Dr. Rajender S, Kushwaha Priyanka, Khedgikar Vikram Adhikary Sulekha, Choudhary Dharmendra, Swarup Jyoti, Kumar Avinash Karvande Anirudha, Verma Ashwni, Sharma Shweta, Pharmaceutical composition for the treatment for Diminution of bone tissue Australia Patent 2014291615 DOF: 12-Jan-16.

3. Trivedi Dr. Ritu, Mishra Dr. Prabhat R, Sangwan Dr. Neelam S Trivedi Dr. Prabodh Singh Dr. Divya, Sangwan Dr. Rajender S, Kushwaha Priyanka, Khedgikar Vikram Adhikary Sulekha, Choudhary Dharmendra, Swarup Jyoti, Kumar Avinash Karvande Anirudha, Verma Ashwni, Sharma Shweta, Pharmaceutical composition for the treatment for Diminution of bone tissue Canada Patent 2917921 DOF: 20-Jan-16.

4. Trivedi Dr. Ritu, Mishra Dr. Prabhat R, Sangwan Dr. Neelam S Trivedi Dr. Prabodh Singh Dr. Divya, Sangwan Dr. Rajender S, Kushwaha Priyanka, Khedgikar Vikram Adhikary Sulekha, Choudhary Dharmendra, Swarup Jyoti, Kumar Avinash Karvande Anirudha, Verma Ashwni, Sharma Shweta, Pharmaceutical composition for the treatment for Diminution of bone tissue US Patent 14/904981 DOF: 14-Jan-16.

5. Trivedi Dr. Ritu, Mishra Dr. Prabhat R, Sangwan Dr. Neelam S Trivedi Dr. Prabodh Singh Dr. Divya, Sangwan Dr. Rajender S, Kushwaha Priyanka, Khedgikar Vikram Adhikary Sulekha, Choudhary Dharmendra, Swarup Jyoti, Kumar Avinash Karvande Anirudha, Verma Ashwni, Sharma Shweta, Pharmaceutical composition for the treatment for Diminution of bone tissue European Patent 14759347.9 DOF: 20-Jan-16.

6. Trivedi Dr. Ritu, Mishra Dr. Prabhat R, Sangwan Dr. Neelam S Trivedi Dr. Prabodh Singh Dr. Divya, Sangwan Dr. Rajender S, Kushwaha Priyanka, Khedgikar Vikram Adhikary Sulekha, Choudhary Dharmendra, Swarup Jyoti, Kumar Avinash Karvande Anirudha, Verma Ashwni, Sharma Shweta, Pharmaceutical composition for treatment for Diminution of bone tissue PCT Patent PCT/IN2014/000475 DOF: 16-Jul-14.

7. Trivedi Dr. Ritu, Mishra Dr. Prabhat R, Sangwan Dr. Neelam S Trivedi Dr. Prabodh Singh Dr. Divya, Sangwan Dr. Rajender S, Kushwaha Priyanka, Khedgikar Vikram Adhikary Sulekha, Choudhary Dharmendra, Swarup Jyoti, Kumar Avinash Karvande Anirudha, Verma Ashwni, Sharma Shweta, Proteasomal inhibitors useful for osteogenic activity and pharmaceutical composition thereof Indian Patent 2145DEL2013 DOF: 17-Jul-13.

8. Renu Tripathi, Prabhat Ranjan Mishra, Pankaj Dwivedi, Hemlata Dwivedi, Sunil Kumar Singh, Sunil Kumar Puri, Anil Kumar Dwivedi Novel combination Kit for Treatment of Malaria 0064NF2014

9. PR Mishra, Ritu Trivedi, GK Gupta, A Kumar, V Gupta, SK Rath, K Srivastava, N Chattopadhyay Controlled Release Micro-Capsule for osteogenic action Canada Patent 2753993 (2010).