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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

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dc.contributor.authorWang, W.
dc.contributor.authorSong, Y.
dc.contributor.authorPetrovski, K.
dc.contributor.authorEats, P.
dc.contributor.authorTrott, D.
dc.contributor.authorWong, H.
dc.contributor.authorPage, S.
dc.contributor.authorPerry, J.
dc.contributor.authorGarg, S.
dc.date.issued2015
dc.description.abstractBACKGROUND: 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.
dc.identifier.citationDrug Design, Development and Therapy, 2015; 9:631-642
dc.identifier.doi10.2147/DDDT.S74731
dc.identifier.issn1177-8881
dc.identifier.issn1177-8881
dc.identifier.orcidPetrovski, K. [0000-0003-4016-2576]
dc.identifier.orcidEats, P. [0000-0002-1151-5830]
dc.identifier.orcidTrott, D. [0000-0002-8297-5770]
dc.identifier.orcidGarg, S. [0000-0001-7253-2629]
dc.identifier.urihttps://hdl.handle.net/11541.2/111963
dc.language.isoen
dc.publisherDOVE MEDICAL PRESS LTD
dc.relation.fundingLuoda Pharma
dc.rightsCopyright 2015. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution - Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php
dc.source.urihttps://doi.org/10.2147/DDDT.S74731
dc.subjectMammary Glands, Animal
dc.subjectMilk
dc.subjectAnimals
dc.subjectCattle
dc.subjectStreptococcal Infections
dc.subjectMastitis, Bovine
dc.subjectPovidone
dc.subjectLasalocid
dc.subjectAnti-Bacterial Agents
dc.subjectCalorimetry, Differential Scanning
dc.subjectSpectroscopy, Fourier Transform Infrared
dc.subjectMicrobial Sensitivity Tests
dc.subjectDrug Administration Routes
dc.subjectKinetics
dc.subjectChemistry, Pharmaceutical
dc.subjectSolubility
dc.subjectDairying
dc.subjectFemale
dc.subjectNanoparticles
dc.titleDevelopment 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
dc.typeJournal article
pubs.publication-statusPublished
ror.fileinfo12143244490001831 13143242510001831 9915984712001831_53114929740001831.pdf
ror.mmsid9915984712001831

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