Self-Assembled Multilayer Films for Time-Controlled Ocular Drug Delivery

Mónica Machado, Gabriela A. Silva, Diogo B. Bitoque, Joana Ferreira, Luís A. Pinto, Jorge Morgado, Quirina Ferreira

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


The patient's compliance on the therapeutics to treat glaucoma is significantly low contributing for a fast evolution of the disease. This article presents an autonomous system with controlled release using an alpha2-adrenergic receptor agonist, brimonidine, usually used to treat glaucoma. More specifically, biocompatible and layer-by-layer drug delivery films containing monolayers with brimonidine encapsulated in polymer-β-cyclodextrin were prepared with the objective to obtain a system able to release precise amounts of drug at specific times. To delay the erosion-controlled drug release, we included nanosheets of graphene oxide and layers of a biodegradable polymer (poly-β-aminoester) between the drug-containing monolayers to obtain a time-controlled drug delivery system. An increase in the number of graphene oxide layers is proportional to the brimonidine release delay and its kinetic release can be tuned as a function of the number of layers. Two types of films with brimonidine encapsulated in β-cyclodextrin were analyzed. One of them composed of barrier layers with PBAE and another with two types of barrier layers, PBAE and graphene oxide. The results indicate that one graphene oxide bilayer can delay the brimonidine release for more than 24 h. In vitro assays confirmed that the films have a cell viability of 100%.

Original languageEnglish
Pages (from-to)4173-4180
JournalACS Applied Bio Materials
Issue number10
Publication statusPublished - 21 Oct 2019


  • brimonidine
  • drug-delivery
  • glaucoma
  • layer-by-layer technique
  • self-assembly


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