Solid Lipid Nanoparticles for Duodenum Targeted Oral Delivery of Tilmicosin

Abstract

Developing a targeted oral delivery system to improve the efficacy of veterinary antibiotics and reduce their consumption and environmental risks is urgent. To achieve the duodenum-targeted release of tilmicosin, the enteric granule containing tilmicosin-loaded solid lipid nanoparticles (TIL-SLNs) was prepared based on its absorption site and transport characteristics. The in vitro release, release mechanisms, stability, palatability, and pharmacokinetics of the optimum enteric granules were studied. The intestine perfusion indicated that the main absorption site of tilmicosin was shifted to duodenum from ileum by TIL-SLNs, while, the absorption of TIL-SLNs in the duodenum was hindered by P-glycoprotein (P-gp). In contrast with TIL-SLNs, the TIL-SLNs could be more effectively delivered to the duodenum in intact form after enteric coating. Its effective permeability coefficient was enhanced when P-gp inhibitors were added. Compared to commercial premix, although the TIL-SLNs did not improve the oral absorption of tilmicosin, the time to reach peak concentration (Tmax) was obviously shortened. After the enteric coating of the granules containing SLNs and P-gp inhibitor of polysorbate-80, the oral absorption of tilmicosin was improved 2.72 fold, and the Tmax was shortened by 2 h. The combination of duodenum-targeted release and P-gp inhibitors was an effective method to improve the oral absorption of tilmicosin.

<p>Enteric-Coated Strategies in Colorectal Cancer Nanoparticle Drug Delivery System</p>

“… Chitosan and Eudragit L-100 Insulin Oral insulin delivery system 130 43. Acrylic acid and methacrylic Rifampicin Sustained release and mucoadhesive delivery 131 44. Poloxamer 188, polyvinyl alcohol, and polyacryl resin II Tilmicosin Prevent gastrointestinal degradation 132 …”

Facile Preparation of Tilmicosin-Loaded Polymeric Nanoparticle with Controlled Properties and Functions

“… 20 − 23 Zhou et al prepared TIM-loaded nanoparticles by hot melting with the ultrasonic emulsification method. 24 In addition, TIM-loaded lipid nanocarriers prepared through the high shear method display excellent storage and gastrointestinal stability and consequently enhanced oral absorption in broilers. 3 , 4 Zhou et al found that TIM-loaded in alginate-chitosan nanogels shows stronger sustained drug release compared with the injection of pure TIM.…”

Current approaches in lipid-based nanocarriers for oral drug delivery

“…This improved the in vivo anti-inflammatory efficacy of the formulation to rats with indomethacin-induced intestinal lesions, significantly reducing the ulcer index and the histological intestinal damage [ 212 ]. The ability of Tween 80 (polysorbate) to inhibit Pgp has also shown a promising role in the bioavailability enhancement of Pgp substrates [ 149 , 156 , 213 ]. In this line, Goo et al observed 4.1-fold permeation enhancement of valsartan, a Pgp substrate, through rat jejunum by its encapsulation in SNEDDS stabilized by Tween 80, as well as a 470% increase in its oral bioavailability in rats.…”

“…Similarly, Zhou et al have recently exploited the potential of polysorbate-80 to inhibit drug efflux. These authors reported higher intestinal permeability of tilmicosin-loaded solid lipid nanoparticles when polysorbate-80 was added as Pgp inhibitor [ 213 ].…”