Development of intramammary delivery systems containing lasalocid for the treatment of bovine mastitis: impact of solubility improvement on safety, efficacy, and milk distribution in dairy cattle

Wen Wang; Yunmei Song; Kiro R. Petrovski; Patricia Eats; Darren J. Trott; Hui San Wong; Stephen W Page; Jeanette Perry; Sanjay Garg

doi:10.2147/DDDT.S74731

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Development of intramammary delivery systems containing lasalocid for the treatment of bovine mastitis: impact of solubility improvement on safety, efficacy, and milk distribution in dairy cattle

Journal article

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Development of intramammary delivery systems containing lasalocid for the treatment of bovine mastitis: impact of solubility improvement on safety, efficacy, and milk distribution in dairy cattle

Wen Wang, Yunmei Song, Kiro R. Petrovski, Patricia Eats, Darren J. Trott, Hui San Wong, Stephen W Page, Jeanette Perry and Sanjay Garg

Drug design, development and therapy, Vol.9, pp.631-642

2014

DOI: https://doi.org/10.2147/DDDT.S74731

PMID: 25653501

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Abstract

Animals

Anti-Bacterial Agents - administration & dosage

Anti-Bacterial Agents - adverse effects

Anti-Bacterial Agents - chemistry

Anti-Bacterial Agents - metabolism

Calorimetry, Differential Scanning

Cattle

Chemistry, Pharmaceutical

Dairying

Drug Administration Routes

Female

Kinetics

Lasalocid - administration & dosage

Lasalocid - adverse effects

Lasalocid - chemistry

Lasalocid - metabolism

Mammary Glands, Animal - drug effects

Mammary Glands, Animal - microbiology

Mammary Glands, Animal - physiopathology

Mastitis, Bovine - diagnosis

Mastitis, Bovine - drug therapy

Mastitis, Bovine - microbiology

Mastitis, Bovine - physiopathology

Microbial Sensitivity Tests

Milk - metabolism

Nanoparticles

Povidone - chemistry

Solubility

Spectroscopy, Fourier Transform Infrared

Streptococcal Infections - diagnosis

Streptococcal Infections - drug therapy

Streptococcal Infections - microbiology

Streptococcal Infections - physiopathology

Background: Mastitis is a major disease of dairy cattle. Given the recent emergence of methicillin-resistant Staphylococcus aureus as a cause of bovine mastitis, new intramammary (IMA) treatments are urgently required. Lasalocid, a member of the polyether ionophore class of antimicrobial agents, has not been previously administered to cows by the IMA route and has favorable characteristics for development as a mastitis treatment. This study aimed to develop an IMA drug delivery system (IMDS) of lasalocid for the treatment of bovine mastitis. Methods: Minimum inhibitory concentrations (MICs) were determined applying the procedures recommended by the Clinical and Laboratory Standards Institute. Solid dispersions (SDs) of lasalocid were prepared and characterized using differential scanning calorimetry and Fourier transform infrared spectroscopy. IMDSs containing lasalocid of micronized, nano-sized, or as SD form were tested for their IMA safety in cows. Therapeutic efficacy of lasalocid IMDSs was tested in a bovine model involving experimental IMA challenge with the mastitis pathogen Streptococcus uberis. Results: Lasalocid demonstrated antimicrobial activity against the major Gram-positive mastitis pathogens including S. aureus (MIC range 0.5–8 µg/mL). The solubility test confirmed limited, ion-strength-dependent water solubility of lasalocid. A kinetic solubility study showed that SDs effectively enhanced water solubility of lasalocid (21–35-fold). Polyvinylpyrrolidone (PVP)-lasalocid SD caused minimum mammary irritation in treated cows and exhibited faster distribution in milk than either nano or microsized lasalocid. IMDSs with PVP-lasalocid SD provided effective treatment with a higher mastitis clinical and microbiological cure rate (66.7%) compared to cloxacillin (62.5%). Conclusion: Lasalocid SD IMDS provided high cure rates and effectiveness in treating bovine mastitis with acceptable safety in treated cows.

Details

Title: Development of intramammary delivery systems containing lasalocid for the treatment of bovine mastitis: impact of solubility improvement on safety, efficacy, and milk distribution in dairy cattle
Authors/Creators: Wen Wang - University of South Australia
Yunmei Song - University of South Australia
Kiro R. Petrovski - The University of Adelaide
Patricia Eats - The University of Adelaide
Darren J. Trott - The University of Adelaide
Hui San Wong - Murdoch University, School of Medical, Molecular and Forensic Sciences
Stephen W Page - Luoda Pharma Pty Ltd, Caringbah, NSW, Australia
Jeanette Perry - The University of Adelaide
Sanjay Garg - University of South Australia
Publication Details: Drug design, development and therapy, Vol.9, pp.631-642
Publisher: Dove Press
Number of pages: 11
Identifiers: 991005806650007891
Murdoch Affiliation: School of Medical, Molecular and Forensic Sciences
Language: English
Resource Type: Journal article

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Source: InCites

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Citation topics: 3 Agriculture, Environment & Ecology; 3.51 Dairy & Animal Sciences; 3.51.1365 Mastitis
Web Of Science research areas: Chemistry, Medicinal; Pharmacology & Pharmacy
ESI research areas: Pharmacology & Toxicology