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Spray Dried Chitosan Microparticles for Intravesical Delivery of Celecoxib: Preparation and Characterization

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Abstract

Purpose

Chitosan microparticles containing celecoxib (CB), were developed as chemoprevention of bladder cancer. Furthermore two inclusion complexes of CB with methyl-β-cyclodextrin (C1 and C2) were prepared to improve the solubility of the drug.

Methods

C1 and C2 were obtained by freeze-drying and characterized in the solid state and in solution. Microparticles loaded with CB or C1 or C2 were prepared by spray drying and fully characterized.

Results

The yield and encapsulation efficiencies of microparticles depended by both the viscosity and the presence of the inclusion complex in the feed medium nebulised. Generally, the microparticles exhibited a spherical shape with mean diameter of approximately 2 μm which was compatible with local intravesical administration using a catheter. The CB release studies from the microparticles allowed us to identify both immediate release systems (microparticles including the complexes) and prolonged release systems (microparticles including CB alone). The latter exhibited good adhesion to the bladder mucosa, as highlighted by a mucoadhesion study. Histological studies revealed a desquamation of the superficial cells when the bladder mucosa was treated with microparticles loaded with CB, while the morphology of the urothelium did not change when it was treated with microparticles loaded with the inclusion complex.

Conclusion

A new CB intravesical formulation than can easily be administered with a catheter and is able to release the drug at the target site for several hours was realized. This new delivery system could be a good alternative to classic oral CB administration.

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Abbreviations

1H-NMR:

Proton nuclear magnetic resonance

CB:

Celecoxib

CH:

Chitosan

DL:

Drug loading

DSC:

Differential scanning calorimetr

EE%:

Efficiency encapsulation percentage

FDA:

Fluorescein diacetate

FT-IR:

Fourier Transform infrared

HPLC:

High performance liquid chromatography

Me-β-CD:

Random methyl-β-cyclodextrin

MPs:

Microparticles

PBS:

Phosphate buffer solution

PDI:

Polydispersity index

SEM:

Scanning electron microscopy

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors acknowledge the financial support of the University of Bari (Italy), and the Inter-University Consortium for Research on the Chemistry of Metal Ions in Biological Systems (C.I.R.C.M.S.B.). We thank Mr. Antonio Palermo for his skilful technical assistance and Dr.Vito Masciopinto for providing us the pig bladders that were used for the mucoadhesion study.

Author information

Authors and Affiliations

  1. Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, 4 Orabona Street, 70125, Bari, Italy

    Angela Lopedota, Annalisa Cutrignelli, Valentino Laquintana, Nunzio Denora, Rosa Maria Iacobazzi, Mara Perrone & Massimo Franco

  2. Istituto Tumori IRCCS Giovanni Paolo II, Bari, Italy

    Rosa Maria Iacobazzi

  3. Department of Chemistry, University of Bari “Aldo Moro”, Bari, Italy

    Elisabetta Fanizza

  4. CNR-Institute for Physical and Chemical Processes UOS, Bari, Italy

    Elisabetta Fanizza & Nicoletta Depalo

  5. Department of Biology, Section of Animal and Environmental Biology, University of Bari “Aldo Moro”, Bari, Italy

    Maria Mastrodonato & Donatella Mentino

  6. Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas, USA

    Antonio Lopalco

Authors
  1. Angela Lopedota
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  2. Annalisa Cutrignelli
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  6. Mara Perrone
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  7. Elisabetta Fanizza
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  8. Maria Mastrodonato
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  9. Donatella Mentino
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  10. Antonio Lopalco
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  11. Nicoletta Depalo
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  12. Massimo Franco
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Corresponding author

Correspondence to Angela Lopedota.

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Lopedota, A., Cutrignelli, A., Laquintana, V. et al. Spray Dried Chitosan Microparticles for Intravesical Delivery of Celecoxib: Preparation and Characterization. Pharm Res 33, 2195–2208 (2016). https://doi.org/10.1007/s11095-016-1956-7

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  • DOI: https://doi.org/10.1007/s11095-016-1956-7

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