Posted by Thorsteinn Loftsson recently published a series of review articles which sums up his advances in ophthalmic drug delivery. This blog entry is just a short recollection of the main points of the writings to spark some interest in reading the articles in detail. Thorsteinn does not need to be introduced to friends of cyclodextrins, his group in Reykjavík, Iceland is an important center for studying pharmaceutical applications of cyclodextrins, together with Einar Stefánsson. He is a co-founder of the company Oculis, and he was the PhD supervisor and mentor of me alongside many other students. He still publishes a lot together with Phatsawee Janssok, from whom I listed 2 reviews from recently.
The year 2022 started with an educational review article about “Topical drug delivery to the retina: obstacles and routes to success” [1]. In this review after introducing retinal diseases and the anatomy of the eye, BCS Classification and the Lipinski’s rule, he points out the main difficulties in retinal drug delivery, listing the 6 main obstacles encountered by drug molecules permeating from the surface into the eye and gives expert advice about how to improve the bioavailability of topical formulations by improving the residence time of the formulation on the eye surface and also maintaining a high concentration of the active on the eye surface and and that the drug concentration needs to be close to saturation concentration in order to partition the dissolved drug molecules into the membrane.
In the review written together with Einar Stefánsson they summarized their long collaboration in ophthalmic drug delivery in the article entitled “Aqueous eye drops containing drug/cyclodextrin
nanoparticles deliver therapeutic drug concentrations to both anterior and posterior segment” [2]. The main focus of the review is on dorzolamide/gamma-cyclodextrin and dexamethasone/gamma-cyclodextrin formulations and the route from preclinical development of cyclodextrin-based eye drops to clinical studies summarizing their most interesting results. They point out the safety of gamma-cyclodextrin (regarded as an inert substance by the FDA), and also that the formulations themselves were well tolerated in comparison to some non-cyclodextrin formulations of the same drugs. The clinical development for diabetic macular edema and postcataract surgery inflammation is ongoing by Oculis.
With Phatsawee Jansook, they published a review, titled “Self-assembled γ-cyclodextrin as nanocarriers for enhanced ocular drug bioavailability” [3], summarizing their collaboration starting from Phatsawee’s PhD project with Prof. Loftsson up to their current research. After introducing gamma-cyclodextrin and its derivatives, their physicochemical properties and drug solubilization with them, the paper tells about the regulatory status and toxicological profile of gamma-cyclodextrin, showing its safety, and then discusses in detail the synergistic effect of excipients on solubilization, modified gamma-cyclodextrin bases nanotechnology platforms for drug delivery and of course the self-assembled nanoparticle/microparticle formation and their uses in ophthalmic formulations.
Although last year, but Phatsawee Jansook also published another review which combines well all the previously mentioned reviews, titled “Cyclodextrin-based formulation of carbonic anhydrase inhibitors for ocular delivery – A review” [4] focusing on how carbonic anhydrase inhibitors formulated with various cyclodextrins can be used in topical ophthalmic drug delivery for lowering intraocular pressure. The role of cyclodextrins are combined, they can take part as solubilizers, permeation enhancers highlighting the ability of cyclodextrins to form nano- and microparticles and using CDs as nanocarriers.
References:
[1] Loftsson, T. (2022): “Topical drug delivery to the retina: obstacles and routes to success”
Expert Opinion on Drug Delivery, 19(1) 9-21.
DOI: 10.1080/17425247.2022.2017878
https://pubmed.ncbi.nlm.nih.gov/34890514/
[2] Loftsson, T., Stefánsson, E. (2022): “Aqueous eye drops containing drug/cyclodextrin nanoparticles deliver therapeutic drug concentrations to both anterior and posterior segment”
Acta Ophthalmologica, 100(1) 7-25.
DOI: 10.1111/aos.14861
[3] Jansook, P., Loftsson, T. (2022): “Self-assembled γ-cyclodextrin as nanocarriers for enhanced ocular drug bioavailability”
International Journal of Pharmaceutics, 618
DOI: https://doi.org/10.1016/j.ijpharm.2022.121654
[4] Jansook, P., Hnin, H.M., Loftsson, T., Stefánsson, E. (2021): “Cyclodextrin-based formulation of carbonic anhydrase inhibitors for ocular delivery – A review”
International Journal of Pharmaceutics, 606
DOI: https://doi.org/10.1016/j.ijpharm.2021.120955