Cathepsin D Degradable Dendrimer-MPEG-Histone 3-Enrofloxacin Conjugate Nanovehicle for Target Specific Bovine Mastitis Therapy
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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.
KeywordsCathepsin D Bovine mastitis Dendrimer Nanoparticle Histone 3 peptide
Tamil Nadu Veterinary and Animal Sciences University (TANUVAS), Chennai is gratefully acknowledged.
Compliance with Ethical Standards
Conflict of interest
The authors declare no conflicts of interest.
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