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Radiolabeled PLGA Nanoparticles for Effective Targeting of Bendamustine in Tumor Bearing Mice

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A Correction to this article was published on 11 October 2018

This article has been updated

Abstract

Purpose

Bendamustine is an important drug for the treatment of chronic lymphatic leukaemia (CLL), non-Hodgkin lymphoma (NHL). However, its delivery is challenging due to its instability. Current approach reports the development and characterization of bendamustine encapsulated PLGA nanoparticles for the effective targeting to leukemic cells.

Methods

The prepared, bendamustine loaded PLGA nanoparticles (BLPNP) were developed and characterized for particle size, zeta potential and polydispersity index. The formed nanoparticles were further characterized with the help of electron microscopy for surface morphology. The formed nanoparticles were evaluated for cytotoxicity, cell uptake, ROS and cell apoptosis against THP-1 leukemic cells as a part of in vitro evaluation. In vivo organ bio-distribution and tumor regression studies were performed to track in vivo behaviour of BLPNP.

Results

The average particle size was 138.52 ± 3.25 nm, with 0.192 ± 0.036 PDI and − 25.4 ± 1.38 mV zeta potential. TEM images revealed the homogeneous particle size distribution with uniform shape. In vitro release exhibited a sustained drug-release behaviour up to 24 h. Cytotoxicity against THP-1 cells through MTT assay observed IC50 value of 27.8 ± 2.1 μM for BLPNP compared to pure drug, which was 50.42 ± 3.4 μM. Moreover, in vitro studies like cell-uptake and cell apoptosis studies further confirmed the higher accumulation of BLPNP in comparison to the pure drug. Organ distribution and tumor regression studies were performed to track in vivo behaviour of bendamustine loaded nanoparticles.

Conclusion

The overall study described a promising approach in terms of safety, least erythrocytic toxicity, better IC50 value with enhance tumor targeting and regression.

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Change history

  • 11 October 2018

    The typesetter did not use the Fig. 6 provided by the author with his proof corrections, and instead duplicated Fig. 7 by the Fig. 6 caption. The original article has been corrected.

Abbreviations

BLPNP:

Bendamustine loaded PLGA nanoparticles

CDDS:

Controlled drug delivery systems

CLL:

Chronic lymphatic leukaemia

DCM:

Dichloromethane

EAT:

Ehrlich ascites tumor

EPR:

Enhanced permeability and retention

FACS:

Fluorescence assisted cell sorting

FITC:

Fluorescein isothiocyanate

ITLC:

Instant thin layer chromatography

NHL:

Non-Hodgkin lymphoma

NPs:

Nanoparticles

PI:

Propidium iodide

PLGA:

Poly lactide-co-glycolic acid

PNP:

Blank PLGA nanoparticles

PVA:

Polyvinyl alcohol

TEM:

Transmission electron microscope

References

  1. Zhang Y, Chan HF, Leong KW. Advanced material and processing for drug delivery: the past and future. Adv Drug Deliv Rev. 2013;65:104–20.

    Article  CAS  Google Scholar 

  2. Safari J, Zarnegar Z. Advanced drug delivery systems: nanotechnology of health design a review. J Saudi Chem Soc. 2014;18:85–99.

    Article  CAS  Google Scholar 

  3. Naahidi S, Jafari M, Edalat F, Raymond K, Khademhosseini A, Chen P. Biocompatibility of engineered nanoparticles for drug delivery. J Control Release. 2013;166:182–94.

    Article  CAS  Google Scholar 

  4. Danhier F, Feron O, Preat V. To exploit the tumor microenvironment: passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J Control Release. 2010;148:135–46.

    Article  CAS  Google Scholar 

  5. Danhier F, Ansorena E, Silva JM, Coco R, Breton AL, Preat V. PLGA-based nanoparticles: an overview of biomedical applications. J Control Release. 2012;161:505–22.

    Article  CAS  Google Scholar 

  6. Khan I, Gothwal A, Sharma AK, Kesharwani P, Gupta L, Iyer A, et al. PLGA nanoparticles and their versatile role in anticancer drug delivery. Critical Rev Therap Drug Carr System. 2016;33(2):159–93.

    Article  Google Scholar 

  7. Acharya S, Sahoo SK. PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. Adv Drug Deliv Rev. 2011;62:170–83.

    Article  Google Scholar 

  8. Khan I, Gothwal A, Sharma AK, Qayum A, Singh SK, Gupta U. Biodegradable nano-architectural PEGylated approach for the improved stability and anticancer efficacy of bendamustine. Int J Bio Macromol. 2016;92:1242–51.

    Article  CAS  Google Scholar 

  9. Gothwal A, Khan I, Kumar P, Raza K, Kaul A, Mishra AK, et al. Bendamustine-PAMAM conjugates for improved apoptosis, efficacy, and in vivo pharmacokinetics: a sustainable delivery tactic. Mol Pharm. 2018;15:2084–97.

    Article  Google Scholar 

  10. Thomas SC, Sharma H, Rawat P, Verma AK, Leekha A, Kumaar V, et al. Synergistic anticancer efficacy of Bendamustine hydrochloride loaded bioactive hydroxyapatite nanoparticles: in-vitro, ex-vivo and in-vivo evaluation. Colloids Surfaces B: Biointerfaces. 2016;146:852–60.

  11. Bhandari J, Mishra H, Mishra PK, Wimmer R, Ahmad FJ, Talegaonkar S. Cellulose nanofiber aerogel as a promising biomaterial for customized oral drug delivery. Int J Nanomedicine. 2017;12:2021–31.

    Article  CAS  Google Scholar 

  12. Kalimuthu K, Lubin BC, Bazylevich A, Gellerman G, Shpilberg O, Luboshits G, et al. Gold nanoparticles stabilize peptide-drug-conjugates for sustained targeted drug delivery to cancer cells. J Nanobiotech. 2018:16–34.

  13. Thomas SC, Madaan T, Iqbal Z, Talegaonkar S. Box-Behnken Design of Experiment Assisted Development and Optimization of Bendamustine HCl loaded hydroxyapatite nanoparticles. Current Drug Deliv. 2018;15:000–0.

    Article  CAS  Google Scholar 

  14. Singh Y, Chandrashekhar A, Meher JG, Durga KK, Viswanadham R, Pawar VK, et al. Nanosized complexation assemblies housed inside reverse micelles churn out monocytic delivery cores for bendamustine hydrochloride. Euro J Pharm Biopharm. 2017;113:198–10.

    Article  CAS  Google Scholar 

  15. Pencheva E, Bogomilova A, Koseva N, Obreshkova D, Troev K. HPLC study on the stability of bendamustine hydrochloride immobilized onto polyphosphoesters. J Pharm Biomed Anal. 2008;48:1143–50.

    Article  CAS  Google Scholar 

  16. Singhai AK, Jain S, Jain NK. Evaluation of an aqueous injection of Ketoprofen. Pharmazie. 1997;52:149–51.

    CAS  PubMed  Google Scholar 

  17. Agarwal P, Gupta U, Jain NK. Glycoconjugated peptide dendrimers-based nanoparticulate system for the delivery of chloroquine phosphate. Biomaterials. 2007;28:3349–59.

    Article  Google Scholar 

  18. ashe HB, Babbar AK, Jain S, Sharma RK, Mishra AK, Asthana A, et al. Investigations on biodistribution of technetium-99m-labeled carbohydrate-coated poly(propylene imine) dendrimers. Nanomedicine: Nanotech Biol Medicine. 2007;3:120–7.

    Article  Google Scholar 

  19. Naik S, Patel D, Chuttani K, Mishra AK, Misra AN. In vitro mechanistic study of cell death and in vivo performance evaluation of RGD grafted PEGylated docetaxel liposomes in breast cancer. Nanomedicine: Nanotech Bio Medicine. 2012;8:951–62.

    Article  CAS  Google Scholar 

  20. Pathak A, Kumar P, Chuttani K, Jain S, Mishra AK, Vyas SP, et al. Gene expression, biodistribution, and Pharmacoscintigraphic evaluation of chondroitin sulfate PEI Nanoconstructs mediated tumor gene therapy. ACS Nano. 2009;3:1493–505.

    Article  CAS  Google Scholar 

  21. Wang H, Zhao Y, Wu Y, Hu YL, Nan K, Nie G, et al. Enhanced anti-tumor efficacy by co-delivery of doxorubicin and paclitaxel with amphiphilic methoxy PEG-PLGA copolymer nanoparticles. Biomaterials. 2011;32:8281–90.

    Article  CAS  Google Scholar 

  22. Gupta U, Sharma S, Khan I, Gothwal A, Sharma AK, Singh Y, et al. Enhanced apoptotic and anticancer potential of paclitaxel loaded biodegradable nanoparticles based on chitosan. Int J Biol Macromol. 2017;98:810–9.

    Article  CAS  Google Scholar 

  23. Upadhyay S, Khan I, Gothwal A, Pachouri P, Bhaskar N, Gupta UD, et al. Conjugated and entrapped HPMA-PLA nano-polymeric micelles based dual delivery of first line anti TB drugs: improved and safe drug delivery against sensitive and resistant Mycobacterium Tuberculosis. Pharm Res. 2017;34:1944–55.

    Article  CAS  Google Scholar 

  24. Singh P, Gupta U, Asthana A, Jain NK. Folate and folate-PEG-PAMAM dendrimers: synthesis, characterization and targeted anticancer drug delivery potential in tumor induced mice. Bioconjug Chem. 2008;19(19):2239–52.

    Article  CAS  Google Scholar 

  25. Gupta M, Chashoo G, Sharma PR, Saxena AK, Gupta PN, Agarwal GP, et al. Dual targeted polymeric nanoparticles based on tumor endothelium and tumor cells for enhanced antitumor drug deliver. Mol Pharm. 2014;11:697–715.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandarsindri, Ajmer, Rajasthan, 305817, India

    Iliyas Khan, Avinash Gothwal & Umesh Gupta

  2. Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, New Delhi, 110054, India

    Ankur Kaul, Rashi Mathur & Anil Kumar Mishra

Authors
  1. Iliyas Khan
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  2. Avinash Gothwal
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  3. Ankur Kaul
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  4. Rashi Mathur
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  5. Anil Kumar Mishra
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  6. Umesh Gupta
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Corresponding author

Correspondence to Umesh Gupta.

Additional information

This article has been revised to correct the error in figure 6.

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Khan, I., Gothwal, A., Kaul, A. et al. Radiolabeled PLGA Nanoparticles for Effective Targeting of Bendamustine in Tumor Bearing Mice. Pharm Res 35, 200 (2018). https://doi.org/10.1007/s11095-018-2482-6

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  • DOI: https://doi.org/10.1007/s11095-018-2482-6

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