Liposomal diclofenac eye drop formulations targeting the retina: Formulation stability improvement using surface modification of liposomes

• Published in: International journal of pharmaceutics 2012-10, Vol.436 (1-2), p.564-567
• Main Authors: Fujisawa, Takuya, Miyai, Hiroko, Hironaka, Kohei, Tsukamoto, Toshimasa, Tahara, Kohei, Tozuka, Yuichi, Ito, Masaki, Takeuchi, Hirofumi
• Format: Article
• Language: English
• Subjects: acetates; Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; calcium; Calcium acetate gradient method; Chemistry, Pharmaceutical; Diclofenac; Diclofenac - administration & dosage; Diclofenac - chemistry; Diclofenac - pharmacokinetics; Drug Stability; encapsulation; Eye drop; Liposome; Liposomes; Ophthalmic Solutions; Particle Size; polyvinyl alcohol; Polyvinyl Alcohol - administration & dosage; Polyvinyl Alcohol - chemistry; Polyvinyl Alcohol - pharmacokinetics; PVA; Rabbits; Retina; Retina - metabolism; Surface Properties
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2012.07.024

The modifying liposome surface with polyvinyl alcohol or its derivative prevented the liposome aggregation and/or fusion during remote loading process, leading to effective retinal delivery. An efficient liposomal formulation for targeting the retina was produced as an optimal means of distributing therapeutic agents to the retina. Diclofenac was used as a model compound for liposome encapsulation, and the release rate and distribution to the retina were investigated. The calcium acetate gradient method was found to be the optimal method for encapsulating diclofenac into liposomes. Entrapment efficiency using this method was greater than 97%, whereas conventional hydration method achieved 51.3%. The resultant formulation obtained with the gradient method caused aggregation and/or fusion of liposomes. To avoid inhibition of retinal delivery due to the aggregation of the carrier, surface modification was performed simultaneously with the gradient method. The increase in particle size of the liposomal formulation clearly was inhibited for a long time in the presence of polyvinyl alcohol or its derivative. This observation may be explained by surface modification of the liposomes by physisorption or anchoring effect of polymers on the surface of the lipid bilayer. Furthermore, the sustained release profile of the diclofenac formulation was retained after modification. An in vivo animal study revealed that concentration of the accumulated diclofenac in the retina–choroid was enhanced 1.8-fold by surface-modified liposome entrapment compared to that of the unaltered diclofenac solution.