Therapeutic delivery of neuropeptides including oxytocin and somatostatin is associated with numerous difficulties including low stability, low oral bioavailability, and a short half-life in vivo. For delivery to the brain, these issues are exacerbated by difficulties in crossing the blood–brain barrier. Lipid-based nanomaterials may offer specific advantages for the delivery of therapeutic peptides including good biocompatibility, retention of peptide activity, and controlled release properties. Herein we have investigated the use of the lipid bicontinuous cubic phase as a depot formulation for the controlled release of the neuropeptides oxytocin and somatostatin. Retention of the cubic architecture was confirmed up to high peptide concentrations of at least 30 mg mL⁻¹ for both peptides. Encapsulation had only minimal effect on the peptide secondary structure in both cases. Controlled release of the peptides from the cubic phase was diffusion controlled over the first 24 h. The time-dependent self-assembly of somatostatin into nanofibrils within the bicontinuous cubic phase led to a unique two-stage release mechanism, with diffusion-controlled release of the peptide monomer over the first 24 h followed by a much slower linear release of the peptide from the nanofibrils. Results suggest that the lipid bicontinuous cubic phase is a highly prospective nanomaterial for the encapsulation and controlled release of neuropeptide therapeutics.

包括催产素和生长抑素在内的神经肽的治疗性给药涉及许多困难，包括稳定性低，口服生物利用度低和体内半衰期短。为了传递到大脑，穿越血脑屏障的困难使这些问题更加恶化。基于脂质的纳米材料可以为治疗性肽的输送提供特定的优势，包括良好的生物相容性，保留肽的活性以及控释特性。在这里，我们已经研究了脂质双连续立方相作为储库制剂用于神经肽催产素和生长抑素的受控释放。确认了高达30 mg mL ^-1的高肽浓度下立方结构的保留对于两种肽。在两种情况下，封装对肽二级结构的影响都很小。在头24小时内，扩散控制了肽从立方相的释放。生长激素抑制素在双连续立方相内随时间变化的自组装成纳米纤维导致了独特的两阶段释放机制，在最初的24小时内扩散控制释放了肽单体，随后缓慢地线性释放了肽从纳米纤维。结果表明脂质双连续立方相是封装和控制释放神经肽治疗剂的高度有前途的纳米材料。