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PEGylated Erlotinib HCl Injectable Nanoformulation for Improved Bioavailability

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Abstract

The present study was undertaken to synthesize PEGylated monomethoxy poly (ethylene glycol)-poly (ε-Caprolactone) (mPEG-PCL) block copolymer and formulate Erlotinib HCl–loaded mPEG-PCL nanoparticles for enhancing the bioavailability of the drug. Using the ring-opening polymerization technique, PEGylated mPEG-PCL block copolymer was synthesized, and the structure of the copolymer was characterized using FTIR, 1H-NMR, and DSC techniques. The solvent evaporation approach was used to effectively encapsulate Erlotinib HCl within block copolymeric nanoparticles. Erlotinib HCl–loaded mPEG-PCL nanoparticles had a mean particle size of 146.5 ± 2.37 nm and a zeta potential of −27.8 ± 2.77 mV. The nanoparticles had a percent entrapment efficiency of 80.78 ± 0.09%. The in vitro drug release of Erlotinib HCl–loaded copolymeric nanoparticles showed a slow and sustained release behavior which could be maintained for up to 72 h. The Korsmeyer-Peppas fitting findings indicated that the drug release process followed a non-Fickian diffusion mechanism. The pharmacokinetic (PK) behavior of the developed nanoformulation was studied in albino Wistar rats, and the relative bioavailability of the optimized NP formulation given by intravenous route was found to be 187.33%. The PK data suggested that Erlotinib HCl–loaded mPEG-PCL copolymeric nanoparticles can dramatically alter the PK behavior of Erlotinib HCl and greatly improve the drug’s bioavailability by as much as three times when compared to the oral formulation. As a result, it was established that the block copolymeric nanoparticles have promise for the effective encapsulation of Erlotinib HCL for an injectable formulation with increased bioavailability.

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Acknowledgements

The authors would like to thank MSN Laboratories Pvt. Ltd., Formulation division, MSN House, Hyderabad, India, for the gift sample of Erlotinib HCl.

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  1. Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM’s NMIMS Deemed to be University, Mumbai, 400056, India

    Hardik Bhargave, Harsh Nijhawan & Khushwant S. Yadav

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Khushwant Yadav: conceptualization, methodology, investigation, writing, reviewing, and editing final manuscript

Hardik Bhargave: methodology, investigation, writing original draft

Harsh Nijhawan: methodology, validation, writing, reviewing, and editing the manuscript

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Bhargave, H., Nijhawan, H. & Yadav, K.S. PEGylated Erlotinib HCl Injectable Nanoformulation for Improved Bioavailability. AAPS PharmSciTech 24, 101 (2023). https://doi.org/10.1208/s12249-023-02560-5

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