Quinteros Daniela, Vicario-de-la-Torre Marta, Andrés-Guerrero Vanessa, Palma Santiago, Allemandi Daniel, Herrero-Vanrell Rocío, Molina-Martínez Irene T
Department of Pharmacy, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, CONICET, Edificio de Ciencias II, Ciudad Universitaria, Córdoba, Argentina.
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Pharmaceutical Innovation in Ophthalmology Research Group, Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC) and the Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Madrid, Spain.
PLoS One. 2014 Oct 20;9(10):e110344. doi: 10.1371/journal.pone.0110344. eCollection 2014.
For the treatment of chronic ocular diseases such as glaucoma, continuous instillations of eye drops are needed. However, frequent administrations of hypotensive topical formulations can produce adverse ocular surface effects due to the active substance or other components of the formulation, such as preservatives or other excipients. Thus the development of unpreserved formulations that are well tolerated after frequent instillations is an important challenge to improve ophthalmic chronic topical therapies. Furthermore, several components can improve the properties of the formulation in terms of efficacy. In order to achieve the mentioned objectives, we have developed formulations of liposomes (150-200 nm) containing components similar to those in the tear film and loaded with the hypotensive melatonin analog 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT, 100 µM). These formulations were combined with mucoadhesive (sodium hyaluronate or carboxymethylcellulose) or amphiphilic block thermosensitive (poloxamer) polymers to prolong the hypotensive efficacy of the drug. In rabbit eyes, the decrease of intraocular pressure with 5-MCA-NAT-loaded liposomes that were dispersed with 0.2% sodium hyaluronate, 39.1±2.2%, was remarkably higher compared to other liposomes formulated without or with other bioadhesive polymers, and the effect lasted more than 8 hours. According to the results obtained in the present work, these technological strategies could provide an improved modality for delivering therapeutic agents in patients with glaucoma.
对于青光眼等慢性眼部疾病的治疗，需要持续滴注眼药水。然而，由于制剂中的活性物质或其他成分（如防腐剂或其他辅料），频繁使用降眼压局部制剂会产生不良的眼表效应。因此，开发在频繁滴注后耐受性良好的无防腐剂制剂是改善眼科慢性局部治疗的一项重要挑战。此外，几种成分可以在疗效方面改善制剂的性能。为了实现上述目标，我们开发了脂质体（150 - 200纳米）制剂，其含有与泪膜中相似的成分，并负载有降眼压褪黑素类似物5 - 甲氧基羰基氨基 - N - 乙酰色胺（5 - MCA - NAT，100微摩尔）。这些制剂与粘膜粘附性（透明质酸钠或羧甲基纤维素）或两亲性嵌段热敏性（泊洛沙姆）聚合物相结合，以延长药物的降眼压疗效。在兔眼中，与未添加或添加其他生物粘附性聚合物的其他脂质体制剂相比，分散有0.2%透明质酸钠的负载5 - MCA - NAT的脂质体使眼压降低39.1±2.2%，效果显著更高，且作用持续超过8小时。根据本研究获得的结果，这些技术策略可为青光眼患者提供一种改进的治疗药物递送方式。
