Objective: The basic concepts, major mechanisms, technological developments and advantages of the topical application of lipid-based systems (microemulsions, nanoemulsions, liposomes and solid lipid nanoparticles), polymeric systems (hydrogels, contact lenses, polymeric nanoparticles and dendrimers) and physical methods (iontophoresis and sonophoresis) will be reviewed. Key findings: Although very convenient for patients, topical administration of conventional drug formulations for the treatment of eye diseases requires high drug doses, frequent administration and rarely provides high drug bioavailability. Thus, strategies to improve the efficacy of topical treatments have been extensively investigated. In general, the majority of the successful delivery systems are present on the ocular surface over an extended period of time, and these systems typically improve drug bioavailability in the anterior chamber whereas the physical methods facilitate drug penetration over a very short period of time through ocular barriers, such as the cornea and sclera. Summary: Although in the early stages, the combination of these delivery systems with physical methods would appear to be a promising tool to decrease the dose and frequency of administration; thereby, patient compliance and treatment efficacy will be improved.

The potential of rigid nanoparticles to serve as transdermal drug carriers can be greatly enhanced by improving their skin penetration. Therefore, the simultaneous application of ultrasound and sodium lauryl sulfate (referred to as US/SLS) was evaluated as a skin pre-treatment method for enhancing the passive transdermal delivery of nanoparticles. We utilized inductively coupled plasma mass spectrometry and an improved application of confocal microscopy to compare the delivery of 10- and 20-nm cationic, neutral, and anionic quantum dots (QDs) into US/SLS-treated and untreated pig split-thickness skin. Our findings include: (a) ∼0.01% of the QDs penetrate the dermis of untreated skin (which we quantify for the first time), (b) the QDs fully permeate US/SLS-treated skin, (c) the two cationic QDs studied exhibit different extents of skin penetration and dermal clearance, and (d) the QD skin penetration is heterogeneous. We discuss routes of nanoparticle skin penetration and the application of the methods described herein to address conflicting literature reports on nanoparticle skin penetration. We conclude that US/SLS treatment significantly enhances QD transdermal penetration by 500-1300%. Our findings suggest that an optimum surface charge exists for nanoparticle skin penetration, and motivate the application of nanoparticle carriers to US/SLS-treated skin for enhanced transdermal drug delivery.