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Cathepsin D Degradable Dendrimer-MPEG-Histone 3-Enrofloxacin Conjugate Nanovehicle for Target Specific Bovine Mastitis Therapy

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Abstract

Mammary gland overexpresses cathepsin D aspartic enzymes during mastitis. Dendrimer (dend)-methoxy poly(ethylene glycol) (MPEG)-enrofloxacin (enro) conjugate nanoparticles were formulated for targeting mammary gland using cathepsin D and cathepsin D cleavable histone 3 peptide. Histone 3 peptide was conjugated with the carboxylic acid end groups of a dendrimer, which was then conjugated with MPEG amine. The antibacterial agent, enrofloxacin was conjugated with dend-h3-MPEG conjugates. Dend-MPEG-enro conjugates without histone 3 peptide linkage was also synthesized for comparison. These conjugates were converted into nanoparticles using a dialysis procedure. Particle size and surface morphology of the developed nanoparticles were measured using photon correlation spectroscopy and transmission electron microscope. In vitro drug release study of dend-h3-MPEG-enro conjugate nanoparticles and dend-MPEG-enro conjugate nanoparticles was performed by dialysis bag diffusion technique over a period of 48 h. Conjugation of enrofloxacin within dend-h3-MPEG-enro conjugates nanoparticles were assessed using UV–Vis spectrophotometer. The mean (± SD) particle size of the dend-h3-MPEG-enro conjugate nanoparticles were 69.4 ± 43 nm and were spherical and circular in shape. The dend-h3-MPEG-enro conjugates had an absorption peak at 273.8 nm and it confirmed successful conjugation of enrofloxacin. Enrofloxacin was released from the dend-h3-MPEG-enro conjugate nanoparticles via biodegradation of the histone 3 peptide upon exposure to cathepsin D. From this study, it can be suggested that dend-h3-MPEG-enro conjugate nanoparticles could be used to deliver antibacterial drug selectively to the mammary gland by exploiting the over expression of cathepsin D during mastitis.

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Acknowledgements

Tamil Nadu Veterinary and Animal Sciences University (TANUVAS), Chennai is gratefully acknowledged.

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Authors and Affiliations

  1. Veterinary College and Research Institute, Orathanadu, Tamil Nadu, 614625, India

    P. Senthil Kumar

  2. National Institute of Technology, Tiruchirappalli, Tamil Nadu, 620015, India

    Sambandam Anandan

  3. Bharathidasan Institute of Technology, Anna University, Tiruchirappalli, Tamil Nadu, 620024, India

    N. Subramanian

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  1. P. Senthil Kumar
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  2. Sambandam Anandan
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  3. N. Subramanian
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Correspondence to P. Senthil Kumar.

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Senthil Kumar, P., Anandan, S. & Subramanian, N. Cathepsin D Degradable Dendrimer-MPEG-Histone 3-Enrofloxacin Conjugate Nanovehicle for Target Specific Bovine Mastitis Therapy. Int J Pept Res Ther 25, 1451–1458 (2019). https://doi.org/10.1007/s10989-018-9790-x

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  • DOI: https://doi.org/10.1007/s10989-018-9790-x

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