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Pharmaceutical Research

, 35:200 | Cite as

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

  • Iliyas Khan
  • Avinash Gothwal
  • Ankur Kaul
  • Rashi Mathur
  • Anil Kumar Mishra
  • Umesh Gupta
Research Paper

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.

KEY WORDS

bendamustine eat nanoparticles PLGA THP-1 

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

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pharmacy, School of Chemical Sciences and PharmacyCentral University of RajasthanAjmerIndia
  2. 2.Division of Cyclotron and Radiopharmaceutical SciencesInstitute of Nuclear Medicine and Allied SciencesNew DelhiIndia

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