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

Abstract

As one of the effective broad-spectrum antimicrobial and anti-inflammatory drugs, tilmicosin (TIM) is applied extensively in a wide range of veterinary treatments. However, the low bioavailability typically leads to overuse of TIM in practical applications, which can cause residual accumulation in the environment and contamination of foodstuffs. Here, we report a precipitation method that allows us to prepare TIM-loaded poly(methyl methacrylate- co -methacrylic acid) (P(MMA- co -MAA)) nanoparticles. Specifically, TIM and biocompatible P(MMA- co -MAA) are dissolved in methanol and then water is introduced as an antisolvent, which triggers the co-precipitation and leads to well-controlled nanoparticles. Depending on the drug/polymer mass ratio and the total concentration of drug and polymer, the formed nanoparticles display a tunable radius from 27 to 80 nm with a narrow size distribution, a high drug loading content, and a controlled release of TIM. The encapsulation does not interrupt the antibacterial function of TIM while reducing its cytotoxicity enormously. Moreover, the formed nanoparticles could be dried to powder through freeze-drying, and the redispersion of the particles hardly disturbs the particle size, size distribution, and drug loading content. Our study developed a facile and robust precipitation method for the controlled construction of TIM-loaded polymeric nanoparticles with tunable properties and functions, as well as improved biocompatibility, which shall improve the bioavailability of TIM and enhance the practical applications.

Control and Preparation of Quaternized Chitosan and Carboxymethyl Chitosan Nanoscale Polyelectrolyte Complexes Based on Reactive Flash Nanoprecipitation

“…As shown in Figure a, as the flow rate increases from 1 mL/min to 7 mL/min, the radius decreases from 142 nm to around 74 nm, reaching the smallest size, and the size distribution is narrower from 0.31 to 0.24 (Figure a). When the flow rates are higher than 7 mL/min (Re ≈ 406), the size remains constant at around 76 nm, suggesting intensive mixing under these conditions. ,,, These results are consistent with the literature results observed for amphiphilic polymer NPs prepared by the RFNP method, where the NP size becomes independent at a high flow rate at a fixed polymer concentration …”

“…The flow rate and the degree of mixing are the crucial characteristics of RFNP. Rapid mixing induces fast and homogeneous mixing of the polyanion and polycation. ,, We vary the flow rate from 1 mL/min to 10 mL/min [the corresponding Reynolds number (Re) shown in Table S5] for CMCH-QCS, at 0.03 w/v % and 1:2 ratio and maintaining the pH at 5.0. As shown in Figure a, as the flow rate increases from 1 mL/min to 7 mL/min, the radius decreases from 142 nm to around 74 nm, reaching the smallest size, and the size distribution is narrower from 0.31 to 0.24 (Figure a).…”

“…The mixing time is a function of the flow rate. The mixing time (τ mix ) was not short enough to provide a homogeneous micromixing environment at a lower flow rate, resulting in the larger size and broad size distribution of NPs. ,,,, In a word, a higher flow rate enhances the mixing of the polyanion and polycation and shortens the mixing time, increasing the rate of energy dissipation, thus reducing the size of the particles and narrowing the size distribution. RFNP can prevent growth and aggregation faster, thus forming relatively stable NCs. , These results are consistent with those previously reported.…”

Optimization of Tilmicosin-Loaded Nanostructured Lipid Carriers Using Orthogonal Design for Overcoming Oral Administration Obstacle

“…The samples were filtered through a 0.22 µm filter membrane before HPLC analysis. The concentration of TMS was calculated using the standard curve equation (y = 31.314x − 2.0603, R 2 = 0.9999) for HPLC analysis of TMS, which had the good linear pattern over a range from 1 to 20 µg/mL as reported previously [17].…”

“…It is easy to cause an acute cardiotoxic effect when administered by injection owing to its transient high drug concentration [13]; hence, oral administration would be a more suitable delivery method for TMS, but this administration route suffers from problems such as poor water solubility, sensitivity to gastric acid, bitterness, and low bioavailability [14]. Hence, it is reported SLNs [13], silica nanoparticles [15], alginatechitosan nanogels [16] and polymeric nanoparticle [17] were used to load TMS, indicating that a stable, safe, and efficient delivery system should be developed for TMS.…”