Lipid nanoparticles (SLN, NLC): Overcoming the anatomical and physiological barriers of the eye – Part II - Ocular drug-loaded lipid nanoparticles

https://doi.org/10.1016/j.ejpb.2016.10.013Get rights and content

Abstract

In the recent decades, various controlled delivery systems have been introduced with the aim to improve solubility, stability and bioavailability of poorly absorbed drugs. Among all, lipid nanoparticles gather interesting properties as drug or gene delivery carriers. These systems, composed either of solid lipids (SLN) or of solid and liquid lipids (NLC) stabilized with surfactants, combine the advantages of other colloidal particles such as polymeric nanoparticles, fat emulsions and liposomes avoiding their main disadvantages. Lipid nanoparticles represent an interesting approach for eye drug delivery as they can improve the corneal absorption of drugs enhancing their bioavailability. The Generally Recognized as Safe status of formulation excipients, the scaling-up facilities and the possibility of sterilization, make them suitable for industrial production. In this review, the latest findings, potential applications, and challenges related to the use of lipid nanoparticles for ocular drug delivery are comprehensively discussed.

Introduction

The application of lipid nanoparticles for ocular delivery has increased during the past decades, with its different applications such as drug and gene delivery, diagnosis or imaging [1]. Among these carriers, solid lipid nanoparticles (SLN) have been considered one of the promising strategies for the treatment of ocular disorders. These nanoparticles are characterized by a solid lipid core which is stabilized by surfactants in aqueous dispersion, and are able to load lipophilic and hydrophilic drug molecules, and combine the advantages of other colloidal carriers, such as polymeric nanoparticles, fat emulsions, liposomes [2] or niosomes [3], avoiding their disadvantages.

SLN show high physical stability, protection of labile drugs against degradation and excellent in vivo tolerability due to their biocompatibility. However, these systems generally show a low drug payload capacity and high drug expulsion during storage, due to the occurrence of polymorphic transitions of lipid molecules toward more stable configurations during the shelf live [4]. These disadvantages can be overcome by surface modification of the particles and, more recently, by the use of nanostructured lipid carriers (NLC), a second generation of lipid particles containing of solid lipids and liquid lipids, leading to special nanostructures with improved drug incorporation and release properties [5], [6].

This paper offers an overview on lipid nanoparticles (both SLN and NLC) as innovative ophthalmic drug delivery systems designed to enhance the drug’s bioavailability in ocular tissues for the treatment of eye diseases.

Section snippets

Characteristics of lipid nanoparticles as ocular drug delivery systems

Since the introduction of solid lipid nanoparticles (SLN) in pharmacotherapy as drug delivery systems, 25 years ago, different attempts have been carried out to use these systems as alternative to traditional carriers (liposomes or polymeric nanoparticles) suitable for the incorporation of both lipophilic and hydrophilic drugs within the lipid matrix [7], [8].

Solid lipid nanoparticles, based on a physiological and biodegradable/biocompatible lipid matrix (stabilized by surfactants), which is

Lipid nanoparticles for ocular applications

Ocular drug delivery by means of administration of lipid nanoparticles has been the focus of several recent works [20]. Biocompatibility and mucoadhesive properties of lipid nanoparticles (SLN, NLC) improve their interaction with the ocular mucosa, which contributes to prolong the corneal residence time of the loaded drug, increasing its ocular bioavailability, and reducing both local and systemic side effects. SLN and NLC could be designed to treat the most important ocular disorders, such as

Conclusions

Among lipid nanoparticles, SLN and NLC, are solid both at body and room temperatures, a property that contributes for the modulation of the release profile of the loaded drugs and are considered as novel alternatives to ocular drug delivery. SLN and NLC have demonstrated capacity to enhance bioavailability of the most used anti-infectious, anti-inflammatory, anti-glaucoma agents or gene material administered as eye drops. Several advantages of these systems include the physiological composition

Declaration of interest

The authors report no conflict of interests. The authors have not received any financial support from any funding agency of our country or any foreign agency to carry out this work.

Acknowledgments

This work was supported by the Spanish Ministry of Science and Innovation (MAT2014-59134-R projects). The first author ESL acknowledges the support of the Spanish Ministry for the PhD scholarship FPI-MICINN under the reference BES-2012-056083. MLG, ME, and ESL belong to 2014SGR-1023. The authors would also like to acknowledge the financial support from the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, and co-financed by FEDER,

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