Wang Wen, Song Yunmei, Petrovski Kiro, Eats Patricia, Trott Darren J, Wong Hui San, Page Stephen W, Perry Jeanette, Garg Sanjay
School of Pharmacy and Medical Science, University of South Australia Adelaide, SA, Australia.
School of Animal and Veterinary Sciences, University of Adelaide, Adelaide, SA, Australia.
Drug Des Devel Ther. 2015 Jan 22;9:631-42. doi: 10.2147/DDDT.S74731. eCollection 2015.
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.
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.
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%).
Lasalocid SD IMDS provided high cure rates and effectiveness in treating bovine mastitis with acceptable safety in treated cows.
乳腺炎是奶牛的一种主要疾病。鉴于耐甲氧西林金黄色葡萄球菌最近成为牛乳腺炎的病因，迫切需要新的乳房内（IMA）治疗方法。拉沙洛西是聚醚离子载体类抗菌剂的一员，此前尚未通过IMA途径给奶牛使用，且具有作为乳腺炎治疗药物开发的有利特性。本研究旨在开发一种用于治疗牛乳腺炎的拉沙洛西IMA给药系统（IMDS）。
按照临床和实验室标准协会推荐的程序测定最低抑菌浓度（MIC）。制备拉沙洛西的固体分散体（SD），并使用差示扫描量热法和傅里叶变换红外光谱进行表征。测试含有微粉化、纳米级或SD形式拉沙洛西的IMDS在奶牛中的IMA安全性。在一个涉及用乳腺炎病原体乳房链球菌进行实验性IMA攻击的牛模型中测试拉沙洛西IMDS的治疗效果。
拉沙洛西对包括金黄色葡萄球菌在内的主要革兰氏阳性乳腺炎病原体具有抗菌活性（MIC范围为0.5 - 8μg/mL）。溶解度测试证实拉沙洛西的水溶性有限且依赖离子强度。动力学溶解度研究表明SD有效提高了拉沙洛西的水溶性（21 - 35倍）。聚乙烯吡咯烷酮（PVP）-拉沙洛西SD对治疗奶牛的乳腺刺激最小，且在牛奶中的分布比纳米级或微粉化拉沙洛西更快。与氯唑西林（62.5%）相比，含有PVP -拉沙洛西SD的IMDS提供了有效的治疗，乳腺炎临床和微生物治愈率更高（66.7%）。
拉沙洛西SD IMDS在治疗牛乳腺炎方面具有高治愈率和有效性，且在治疗奶牛中具有可接受的安全性。
