research

Liposomal Drug Delivery

Collaborator: Singapore Eye Research Institute (SERI)

The overall objective of this project is to develop sustained release formulations of ocular drugs from liposomes and deliver them into various anatomical regions in the eye. Different classes of drugs such as prostaglandins, antimicrobials and anti-inflammatory are evaluated for sustained release from liposomes to front and back of the eye. Glaucoma is a chronic disease that often leads to blindness. Intraocular pressure (IOP) remains the clinical and modifiable risk factor for this disease. The widely accepted method of treatment involves the use of daily topical eye drops. However, this mode of administration results in variable therapeutic response due to poor patient compliance and chronic side effects from repeated drug administration. We have developed a world’s first sustained release nanomedicine product for glaucoma therapy. This product (LipoLat) has shown sustained IOP lowering for up to 120 days in non-human primates and beyond three months in a First-in-Man clinical trial conducted in Singapore (Ref. 1 and 2). This product has been licensed to a start-up company in Singapore. The developed formulation was stable and safe for administration. Similarly, other prostaglandin derivatives, anti-inflammatory and antimicrobials loaded in liposomes are in the pre-clinical stages of development for sustained release and could provide an alternative therapy for eye diseases in the future.

 

Figure 1: (A) Intraocular pressure measurements. Comparison of intraocular pressure (IOP) measurements between Xalatan® (topical eye drops) and latanoprost loaded EggPC liposomes (subconjunctival injection) in non-human primates. (B) Schematic representation of liposome encapsulated latanoprost and a subconjunctival injection. (C) Intraocular pressure changes of all six human subjects. (D) In vitro latanoprost release from liposomes. All figures have been reprinted (adapted) from ACS Nano and Drug Delivery and Translational Research journals.
Funding agency: National Medical Research Council

Publications:
(1) Wong TT, Novack GD, Natarajan JV, Ho CL, Htoon HM, Venkatraman SS. Nanomedicine for glaucoma: sustained release latanoprost offers a new therapeutic option with substantial benefits over eyedrops. Drug Delivery and Translational Research, doi: 10.1007/s13346-014-0196-9 (2014).

(2) Natarajan JV, Darwitan A, Barathi VA, Ang M, Htoon HM, Boey F, Tam KC, Wong TT, Venkatraman S. Sustained drug release in nanomedicine: a long acting nanocarrier-based formulation for glaucoma. ACS Nano, doi:10.1021/nn4046024 (2014).

(3) Natarajan JV, Ang M, Darwitan A, Wong TT, Venkatraman SS. Nanomedicine for glaucoma: liposomes provide sustained delivery of latanoprost in the eye. International Journal of Nanomedicine, 7, 123–131 (2012).

(4) Natarajan JV, Chattopadhyay S, Ang M, Darwitan A, Foo S, Zhen M, Koo M, Wong TT, Venkatraman SS. Sustained release of an anti-glaucoma drug: demonstration of efficacy of a liposomal formulation in the rabbit eye. PLoS ONE, 6 (9), e24513 (2011).