Quinine hydrochloride (QHCl) has remained a very relevant antimalarial drug 400 years after its effectiveness was discovered. Unlike other antimalarials, the development of resistance to quinine has been slow. Hence, this drug is to date still used for the treatment of severe and cerebral malaria, for malaria treatment in all trimesters of pregnancy, and in combination with doxycycline against multidrug-resistant malaria parasites. The decline in its administration over the years is mainly associated with poor tolerability due to its gastrointestinal (GIT) side effects such as cinchonism, complex dosing regimen and bitter taste, all of which result in poor compliance. Hence, our research was aimed at redesigning quinine using nanotechnology and investigating an alternative route for its administration for the treatment of malaria. QHCl nanosuspension (QHCl-NS) for intranasal administration was prepared using lipid matrices made up of solidified reverse micellar solutions (SRMS) comprising Phospholipon® 90H and lipids (Softisan® 154 or Compritol®) in a 1:2 ratio, while Poloxamer® 188 (P188) and Tween® 80 (T80) were used as a stabilizer and a surfactant, respectively. The QHCl-NS formulated were in the nanosize range (68.60 ± 0.86 to 300.80 ± 10.11 nm), and highly stable during storage, though zeta potential was low (≤6.95 ± 0.416). QHCl-NS achieved above 80% in vitro drug release in 6 h. Ex vivo permeation studies revealed that formulating QHCl as NS resulted in a 5-fold and 56-fold increase in the flux and permeation coefficient, respectively, thereby enhancing permeation through pig nasal mucosa better than plain drug solutions. This implies that the rate of absorption as well as ease of drug permeation through porcine nasal mucosa was impressively enhanced by formulating QHCl as NS. Most importantly, reduction in parasitaemia in mice infected with Plasmodium berghei ANKA by QHCl-NS administered through the intranasal route (51.16%) was comparable to oral administration (52.12%). Therefore, redesigning QHCl as NS for intranasal administration has great potential to serve as a more tolerable option for the treatment of malaria in endemic areas.

中文翻译：

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奎宁：重新设计和改道

盐酸奎宁 (QHCl) 在其有效性被发现 400 年后仍然是一种非常相关的抗疟药。与其他抗疟药不同，对奎宁的耐药性发展缓慢。因此，该药至今仍用于治疗重症和脑型疟疾，用于妊娠所有三个月的疟疾治疗，以及与多西环素联合治疗耐多药疟疾寄生虫。多年来其给药量的下降主要与其胃肠道（GIT）副作用如辛可中毒、复杂的给药方案和苦味导致的耐受性差有关，所有这些都导致依从性差。因此，我们的研究旨在使用纳米技术重新设计奎宁，并研究其治疗疟疾的替代途径。用于鼻内给药的 QHCl 纳米悬浮液 (QHCl-NS) 是使用由固化的反胶束溶液 (SRMS) 组成的脂质基质制备的，该溶液包含 Phospholipon® 90H 和脂质（Softisan® 154 或 Compritol®），比例为 1:2，而 Poloxamer® 188 (P188) 和 Tween® 80 (T80) 分别用作稳定剂和表面活性剂。配制的 QHCl-NS 在纳米尺寸范围内（68.60 ± 0.86 至 300.80 ± 10.11 nm），并且在储存期间高度稳定，尽管 zeta 电位很低（≤6.95 ± 0.416）。QHCl-NS 在 6 小时内实现了 80% 以上的体外药物释放。离体渗透研究表明，将 QHCl 配制成 NS 后，通量和渗透系数分别增加了 5 倍和 56 倍，从而比普通药物溶液更好地增强了猪鼻粘膜的渗透。这意味着通过将 QHCl 配制为 NS，吸收速率以及药物通过猪鼻粘膜渗透的容易程度显着提高。最重要的是，通过鼻内途径给药的 QHCl-NS 在感染伯氏疟原虫 ANKA 的小鼠中寄生虫血症的减少 (51.16%) 与口服给药 (52.12%) 相当。因此，将 QHCl 重新设计为用于鼻内给药的 NS 具有很大的潜力，可以作为疟疾流行地区治疗的更耐受的选择。