School of Pharmacy, Nanchang University, Nanchang, 330006, China.
School of Chemistry, Nanchang University, Nanchang, 330031, China.
Colloids Surf B Biointerfaces. 2019 Sep 1;181:369-378. doi: 10.1016/j.colsurfb.2019.05.061. Epub 2019 May 25.
Solid lipid nanoparticles (SLNs) have been widely used as a vehicle for drug delivery. However, highly ordered lipid lattices and poor storage stability limit their practical application. Highly ordered crystal lattices may result from the low drug payload. In addition, the lipid matrix of SLNs may undergo a polymorphic transition from high energy and disordered modifications to low energy and ordered modifications during storage. This leads to drug expulsion and precipitation. Meanwhile, SLNs are susceptible to particle aggregation and size growth during storage. To improve the performance of SLNs, two comb-shaped amphiphilic macromolecular materials (CAMs), dodecyl inulin (Inu12) and octadecyl inulin (Inu18), were synthesized and utilized as emulsifiers to modify and stabilize SLNs (Inu12/Inu18-SLNs). The results indicated that Inu12 and Inu18 could more effectively reduce the lipid crystallinity and crystal lattice order of fresh SLNs versus Poloxamer 188 and Tween-80. Moreover, after six months of storage at 4 °C or 25 °C, both blank and Cyclosporine A (CsA)-loaded Inu12/Inu18-SLNs had a slower crystal transition than Tween/P188-SLNs. The particle size increases of Inu12/Inu18-SLNs were much smaller than those of Tween/P188-SLNs. The drug encapsulation efficiencies of CsA-loaded Inu12/Inu18-SLNs during storage decreased more slowly than Tween-SLNs. Therefore, Inu12 and Inu18 could more effectively inhibit lipid crystal transition and prevent particle aggregation during storage. This, in turn, leads to better storage physical stability of SLNs. Thus, the Inu12 and Inu18 CAMs were superior to Tween-80 and Poloxamer 188 (common straight-chain surfactants).
固体脂质纳米粒 (SLN) 已被广泛用作药物传递载体。然而，高度有序的脂质晶格和较差的储存稳定性限制了它们的实际应用。高度有序的晶体晶格可能是由于药物载药量低所致。此外，SLN 的脂质基质在储存过程中可能会经历从高能无序修饰到低能有序修饰的多晶型转变。这导致药物排出和沉淀。同时，SLN 在储存过程中容易发生颗粒聚集和粒径增长。为了提高 SLN 的性能，合成了两种梳状两亲性大分子材料（CAM），十二烷基菊糖（Inu12）和十八烷基菊糖（Inu18），并将其用作乳化剂来修饰和稳定 SLN（Inu12/Inu18-SLNs）。结果表明，与泊洛沙姆 188 和吐温 80 相比，Inu12 和 Inu18 可以更有效地降低新鲜 SLN 的脂质结晶度和晶格有序度。此外，在 4°C 或 25°C 下储存 6 个月后，空白和环孢素 A（CsA）负载的 Inu12/Inu18-SLNs 的晶体转变速度均比 Tween/P188-SLNs 慢。Inu12/Inu18-SLNs 的粒径增长明显小于 Tween/P188-SLNs。储存过程中，CsA 负载的 Inu12/Inu18-SLNs 的药物包封效率下降速度比吐温 SLNs 慢。因此，Inu12 和 Inu18 可以更有效地抑制脂质晶体转变并防止颗粒聚集在储存过程中。这反过来又导致 SLN 具有更好的储存物理稳定性。因此，Inu12 和 Inu18 CAM 优于吐温 80 和泊洛沙姆 188（常见的直链表面活性剂）。
