Bessone Carolina Del Valle, Akhlaghi Seyedeh Parinaz, Tártara Luis Ignacio, Quinteros Daniela Alejandra, Loh Watson, Allemandi Daniel Alberto
Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 Córdoba, Argentina.
Institute of Chemistry, University of Campinas (UNICAMP), PO Box 6154, 13083-970 Campinas-SP, Brazil.
Eur J Pharm Sci. 2021 May 1;160:105748. doi: 10.1016/j.ejps.2021.105748. Epub 2021 Feb 7.
Glaucoma is a degenerative optic neuropathy characterized by increased intraocular pressure that if untreated can result in blindness. Ophthalmological drug therapy is a challenge of great clinical importance due to the diversity of ocular biological barriers which commonly causes limited or no effectiveness for drugs delivered through the eye. In this work, we proposed the development of nanosized cubic liquid crystals (cubosomes) as a new drug carrier system for latanoprost, an anti-glaucoma drug. Latanoprost-loaded phytantriol cubosomes (CubLnp) were prepared using a top-down method. Latanoprost concentration in the formulations ranged from 0.00125% to 0.02% w/v. All cubosomes displayed an average size around 200 nm, a low polydispersity index of 0.1 and zeta potential values around -25 mV, with an encapsulation efficiency of about 90%. Structural studies revealed that cubosomes displayed a double-diamond surface, Pn3m cubic-phase structure, and was not affected by drug loading. Calorimetric studies revealed a fast and exothermic interaction between latanoprost and cubosomes. According to in vitro essays, latanoprost release from cubosomes was slow in time, evidencing a sustained release profile. Based on this behavior, the in vivo hypotensive intraocular effect was evaluated by means of the subconjunctival administration of CubLnp in normotensive rabbits. We obtained promising results in comparison with a marketed latanoprost formulation (0.005% w/v).
青光眼是一种退行性视神经病变，其特征是眼内压升高，若不治疗可导致失明。由于眼部生物屏障的多样性，眼科药物治疗是一项具有重大临床意义的挑战，这通常会导致通过眼部给药的药物效果有限或无效。在这项工作中，我们提出开发纳米级立方液晶（立方液晶脂质体）作为抗青光眼药物拉坦前列素的新型药物载体系统。采用自上而下的方法制备了载有拉坦前列素的植烷三醇立方液晶脂质体（CubLnp）。制剂中拉坦前列素的浓度范围为0.00125%至0.02%（w/v）。所有立方液晶脂质体的平均尺寸约为200nm，多分散指数低至0.1，zeta电位值约为-25mV，包封效率约为90%。结构研究表明，立方液晶脂质体呈现双菱形表面、Pn3m立方相结构，且不受药物负载的影响。量热研究表明拉坦前列素与立方液晶脂质体之间存在快速放热相互作用。根据体外试验，拉坦前列素从立方液晶脂质体中的释放随时间缓慢进行，显示出缓释特性。基于这种特性，通过在正常血压兔结膜下注射CubLnp来评估其体内降眼压效果。与市售的拉坦前列素制剂（0.005%，w/v）相比，我们获得了有前景的结果。
