Pharmaceutical Research

, Volume 27, Issue 8, pp 1659–1676 | Cite as

Development of New Localized Drug Delivery System Based on Ceftriaxone-Sulbactam Composite Drug Impregnated Porous Hydroxyapatite: A Systematic Approach for In Vitro and In Vivo Animal Trial

  • Biswanath Kundu
  • Chidambaram Soundrapandian
  • Samit K. Nandi
  • Prasenjit Mukherjee
  • Nandadulal Dandapat
  • Subhasis Roy
  • Bakul K. Datta
  • Tapan K. Mandal
  • Debabrata Basu
  • Rupnarayan N. Bhattacharya
Research Paper

ABSTRACT

Purpose

Present investigation deals with an extensive approach incorporating in vitro and in vivo experimentation to treat chronic osteomyelitis, using hydroxyapatite porous scaffolds.

Materials and Methods

Hydroxyapatite was synthesized in the laboratory by wet chemical method, different porous scaffolds have been fabricated. In vitro studies include variation of porosity with interconnectivity, pore-drug interfacial studies by SEM-EDAX and drug elution studies (by HPLC) both in contact with PBS and SBF at ~37°C. In vivo trials were based on experimental osteomyelitis in rabbit model induced in tibia by Staphylococcus aureus. Characterizations included observation of histopathology, radiology and estimation of drug in both bone and serum for 42 days by HPLC method and subsequent bone-biomaterial interface by SEM.

Results

It was established that lower pore percentage with a distribution of mainly micro-pores were found to be superior over the higher pore percentage both in vitro and in vivo. The criteria was matched with the 50N50H samples which had 50–55% porosity with an average pore size ~110 μm, having higher interconnectivity (10–100 μm), moderately high adsorption efficiency (~50%) when loaded with CFS (drug combinations consisting of irreversible b-lactamase inhibitor and b-lactam antibiotic). CFS release from HAp implants were faster in PBS than SBF. Further, both the results of in vitro and in vivo drug elution after 42 days showed release higher than minimum inhibitory concentration of CFS against Staphylococcus aureus. In vivo studies also proved the superiority of CFS loaded HAp implants than parenteral group based on eradication of infection and new bone formation.

Conclusions

HAp based porous scaffold loaded with CFS and designed porosity (in terms of micro- and macro-porosity, interconnectivity) was found to be an ideal delivery system which could locally, sustainably release the composite antibiotic in reliable manner both in terms of in vitro drug elution behaviour in contact with SBF and in vivo animal trial.

KEY WORDS

ceftriaxone-sulbactam composite in vivo animal trial osteomyelitis and new bone formation porous hydroxyapatite SBF 

ABBREVIATIONS

ASTM

American Society for Testing and Materials

AUC

Area under the curve

CFA

Colony-forming unit

CFS

Combination of CFT and SUL drug

CFT

Ceftriaxone sodium

FESEM

Field emission scanning electron microscopy

FTIR

Fourier-transformed infrared spectroscopy

HAp

Hydroxyapatite

HPLC

High performance liquid chromatography

MIC

Minimum inhibitory concentration

PBS

Phosphate buffered saline

PMMA

Poly-methyl methacrylate

RBC

Red blood cell

SBF

Simulated body fluid

SEM-EDAX

Scanning electron microscopy-Energy dispersive analysis of X-ray

SUL

Sulbactam sodium

XRD

X-ray diffraction

Notes

ACKNOWLEDGEMENTS

The authors wish to express their sincere thanks for the financial support by Department of Science and Technology, India [T.1 (7)/TIFA/2006-CGCRI] and the Director, CGCRI, India and Vice Chancellor, West Bengal University of Animal and Fishery Sciences, Kolkata, India for their generous and kind support to this work. All the personnel related to the characterization of the materials are sincerely acknowledged.

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Biswanath Kundu
    • 1
  • Chidambaram Soundrapandian
    • 1
  • Samit K. Nandi
    • 2
  • Prasenjit Mukherjee
    • 2
  • Nandadulal Dandapat
    • 1
  • Subhasis Roy
    • 2
  • Bakul K. Datta
    • 3
  • Tapan K. Mandal
    • 3
  • Debabrata Basu
    • 1
  • Rupnarayan N. Bhattacharya
    • 4
  1. 1.Bioceramics and Coating DivisionCentral Glass and Ceramic Research InstituteKolkataIndia
  2. 2.Department of Veterinary Surgery and RadiologyWest Bengal University of Animal and Fishery SciencesKolkataIndia
  3. 3.Department of Veterinary Pharmacology and ToxicologyWest Bengal University of Animal and Fishery SciencesKolkataIndia
  4. 4.Department of Plastic SurgeryR.G. Kar Medical College and HospitalKolkataIndia

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