Woraphatphadung Thisirak, Sajomsang Warayuth, Gonil Pattarapond, Treetong Alongkot, Akkaramongkolporn Prasert, Ngawhirunpat Tanasait, Opanasopit Praneet
Pharmaceutical Development of Green Innovations Group (PDGIG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.
National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathum Thani 12120, Thailand.
Int J Pharm. 2016 Jan 30;497(1-2):150-60. doi: 10.1016/j.ijpharm.2015.12.009. Epub 2015 Dec 4.
The amphiphilic chitosan derivatives, N-naphthyl-N,O-succinyl chitosan (NSCS), N-octyl-N-O-succinyl chitosan (OSCS) and N-benzyl-N,O-succinyl chitosan (BSCS), were synthesized. Meloxicam (MX) was loaded into polymeric micelles (PMs), and the effects of hydrophobic moieties of the inner core segment on the loading efficiency, stability of MX-loaded PMs, cytotoxicity, drug release, and porcine small intestine permeation were investigated. Among the hydrophobic cores, the N-octyl moiety revealed the highest MX loading efficiency and most stable MX-loaded PMs compared to the other hydrophobic cores. All PMs were spherically shaped (size 213-282 nm) and had low toxicity against Caco-2 cells. The release of MX from PMs was found to be dependent on both hydrophobic cores and hydrophilic shells. In acidic medium at 0-2h, low cumulative MX release was obtained in the MX-loaded OSCS PMs compared to MX-loaded NSCS PMs and MX-loaded BSCS PMs as well as MX free drug. However, when the pH was increased to 6.8, the MX release significantly increased in all MX-loaded PMs. Furthermore, the intestinal permeation rates of MX from all MX-loaded PMs were not significantly different. These results suggest that MX was successfully incorporated into the PMs at high efficiency and good stability by optimizing the hydrophobic moieties of the inner core segments.
合成了两亲性壳聚糖衍生物，即N-萘基-N,O-琥珀酰壳聚糖（NSCS）、N-辛基-N,O-琥珀酰壳聚糖（OSCS）和N-苄基-N,O-琥珀酰壳聚糖（BSCS）。将美洛昔康（MX）载入聚合物胶束（PMs）中，并研究了内核段疏水基团对载MX的PMs的载药效率、稳定性、细胞毒性、药物释放以及猪小肠渗透的影响。在疏水内核中，与其他疏水内核相比，N-辛基部分显示出最高的MX载药效率和最稳定的载MX的PMs。所有PMs均呈球形（尺寸为213 - 282 nm），对Caco-2细胞毒性较低。发现MX从PMs中的释放既取决于疏水内核也取决于亲水外壳。在0 - 2小时的酸性介质中，与载MX的NSCS PMs、载MX的BSCS PMs以及游离MX药物相比，载MX的OSCS PMs中MX的累积释放量较低。然而，当pH值升至6.8时，所有载MX的PMs中MX的释放均显著增加。此外，所有载MX的PMs中MX的肠道渗透速率没有显著差异。这些结果表明，通过优化内核段的疏水基团，MX得以高效且稳定地成功载入PMs中。
