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Glycine-Poly-L-Lactic Acid Copolymeric Nanoparticles for the Efficient Delivery of Bortezomib

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Abstract

Purpose

Bortezomib (BTZ) is a proteasome inhibitor used for multiple myeloma and mantle cell lymphoma treatment. BTZ’s aqueous in solubility is the main hindrance in its successful development as a commercial formulation. The main objective of the present study is to develop and characterize folic acid-glycine-poly-L-lactic acid (FA-Gly4-PLA) based nanoformulation (NPs) to improve solubility and efficacy of BTZ.

Methods

BTZ loaded FA-Gly4-PLA NPs were prepared and characterized for size, zeta potential, in vitro studies such as release, kinetics modeling, hemolytic toxicity, and cell line-based studies (Reactive Oxygen Species: ROS and cytotoxicity).

Results

BTZ loaded NPs (BTZ-loaded FA-Gly4-PLA) and blank NPs (FA-Gly4-PLA) size, zeta, and PDI were found to be 110 ± 8.1 nm, 13.7 ± 1.01 mV, 0.19 ± 0.03 and 198 ± 9.01 nm, 8.63 ± 0.21 mV, 0.21 ± 0.08 respectively. The percent encapsulation efficiency (% EE) and percent drug loading (% DL) of BTZ loaded FA-Gly4-PLA NPs was calculated to be 78.3 ± 4.1 and 12.38 ± 2.1. The Scanning Electron Microscopy (SEM) showed that NPs were slightly biconcave in shape. The in vitro release of BTZ from FA-Gly4-PLA NPs resulted in the sustained manner. The prepared NPs were less hemolytic than BTZ.

Conclusions

BTZ loaded Gly4-PLA NPs apoptotic index was found to be much higher than BTZ but lesser than BTZ loaded FA-Gly4-PLA against breast cancer cell lines (MDA-MB-231). ROS intracellular assessment assay indicated that BTZ and BTZ loaded FA-Gly4-PLA NPs exhibited higher ROS production. Conclusively, the BTZ loaded FA-Gly4-PLA NPs were able to encapsulate more BTZ than BTZ loaded Gly4-PLA NPs and were found to be more effective as per as in vitro anti-cancer effect is concerned.

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Abbreviations

AFM:

Atomic Force Microscopy

BTZ:

Bortezomib

CLSM:

Confocal laser microscope

EDA:

Ethylene diamine

ER:

Estrogen receptors

FA:

Folic acid

Gly:

Glycine

HER:

Human epidermal growth factor receptor

NPs:

Nanoparticles

PDI:

Polydispersity Index

PLA:

Poly-L-lactic acid

SEM:

Scanning Electron Microscopy

TNBC:

Triple Negative breast cancer

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Acknowledgments and Disclosures

The authors would like to acknowledge the financial support received from Department of Science and Technology and University Grants Commission, New Delhi, India to Dr. Umesh Gupta in the form of DST Startup Research Grant (for Young Scientists).

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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

    Sudhakar Rajoria, Sarita Rani & Umesh Gupta

  2. Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, SAS Nagar, Mohali, Punjab, 160062, India

    Dasharath Chaudhari & Sanyog Jain

Authors
  1. Sudhakar Rajoria
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  2. Sarita Rani
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  3. Dasharath Chaudhari
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Correspondence to Umesh Gupta.

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Rajoria, S., Rani, S., Chaudhari, D. et al. Glycine-Poly-L-Lactic Acid Copolymeric Nanoparticles for the Efficient Delivery of Bortezomib. Pharm Res 36, 160 (2019). https://doi.org/10.1007/s11095-019-2686-4

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