Lipid nanoparticles (SLN, NLC): Overcoming the anatomical and physiological barriers of the eye – Part II - Ocular drug-loaded lipid nanoparticles
Graphical abstract
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,
References (96)
- et al.
Liposome coated with low molecular weight Chitosan and its potential use in ocular drug delivery
Int. J. Pharm.
(2009) - et al.
Design and evaluation of controlled-release niosomes and discomes for naltrexone hydrochloride ocular delivery
J. Pharm. Sci.
(2011) - et al.
Nanostructured lipid matrices for improved microencapsulation of drugs
Int. J. Pharm.
(2002) - et al.
Solid lipid nanoparticles (SLN) for controlled drug delivery – a review of the state of the art
Eur. J. Pharm. Biopharm.
(2000) - et al.
Nanotoxicology applied to solid lipid nanoparticles and nanostructured lipid carriers – a systematic review of in vitro data
Eur. J. Pharm. Biopharm.
(2014) - et al.
Nanostructured lipid carriers: promising drug delivery systems for future clinics
Nanomedicine
(2016) Solid lipid nanoparticles Production, characterization and applications
Adv. Drug Deliv. Rev.
(2001)- et al.
Cationic liposomes as potential carriers for ocular administration of peptides with anti-herpetic activity
Int. J. Pharm.
(2006) - et al.
Design of cationic lipid nanoparticles for ocular delivery: development, characterization and cytotoxicity
Int. J. Pharm.
(2014) - et al.
Influence of different surfactants on the technological properties and in vivo ocular tolerability of lipid nanoparticles
Int. J. Pharm.
(2014)