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Fabrication of protein-loaded PLGA nanoparticles: effect of selected formulation variables on particle size and release profile

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Abstract

In this study, the processing conditions for fabricating bovine serum albumin (BSA)-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles via a water/oil/water double emulsion technique were adjusted and release profiles were studied. Particle size and surface morphology of the BSA-loaded PLGA nanoparticles were comprehensively controlled as a function of processing determinants. The nanoparticles were intended as a carrier for controlled delivery of therapeutic proteins; however, BSA was chosen as a hydrophilic model protein encapsulated within PLGA nanoparticles to investigate the effective formulation parameters. Several key processing parameters were changed including surfactant(s) concentration in the internal and external aqueous phases, BSA concentration, poly(vinyl alcohol) (PVA) characteristics, and power of ultrasonicator probe to investigate their effects on the morphological characteristics and size distribution of the nanoparticles (NPs). The prepared NPs showed spherical shape with smooth and pore-free surfaces along with a relatively narrow particle size distribution. The mean particle size of the optimized formulation was 251.3 ± 8.5 nm, which is ideal for drug delivery applications. Our results demonstrate that using PVA with Mw 13–23 kDa and degree of hydrolysis approximately 87–89 % yields better results than PVA of higher molecular weight and higher degree of hydrolysis. Surfactants concentrations in internal (Span 60) and external phase (Tween 80) of the emulsions, which play a key role in determining NP characteristics and cumulative percentage BSA released, were optimized at 14 % (w/w) and 4 % (w/v), respectively. Optimal level of ultrasonication power (50 W) was also determined. According to the results, the optimized protein-loaded NPs with proper shape, size, and surface properties were prepared and these may act as a good candidate for protein delivery.

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Acknowledgments

The authors are grateful to the Iran National Science Foundation (INSF) for the financial assistance (grant no. 89003650) and Iran Polymer and Petrochemical Institute for technical support. We would especially like to thank Dr Manizheh Motavalian for kindly providing freeze-drying facilities during the particle fabrication, and Mrs Khosravi and Mr Pirhajatie for performing SEM and TEM analyses.

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Authors and Affiliations

  1. Department of Anatomy, Tehran University of Medical Sciences, P.O. Box 14496/14525, Tehran, Iran

    Monireh Azizi, Mohammadtaghi Joghataei & Mehrdad Bakhtiary

  2. Novel Drug Delivery Systems Department, Iran Polymer and Petrochemical Institute, P.O. Box 14965/115, Tehran, Iran

    Monireh Azizi, Farhid Farahmandghavi, Mohammad Imani & Fariba Ghazizadeh

  3. Cellular and Molecular Research Center, Tehran University of Medical Sciences, P.O. Box 14496/14535, Tehran, Iran

    Monireh Azizi, Mohammadtaghi Joghataei & Mehrdad Bakhtiary

  4. Biomaterial Department, Iran Polymer and Petrochemical Institute, P.O. Box 14965/115, Tehran, Iran

    Mojgan Zandi

  5. Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Farid Abedin Dorkoosh

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  1. Monireh Azizi
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Correspondence to Farhid Farahmandghavi.

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Azizi, M., Farahmandghavi, F., Joghataei, M. et al. Fabrication of protein-loaded PLGA nanoparticles: effect of selected formulation variables on particle size and release profile. J Polym Res 20, 110 (2013). https://doi.org/10.1007/s10965-013-0110-z

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  • DOI: https://doi.org/10.1007/s10965-013-0110-z

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