Journal
MEDICAL HYPOTHESES
Volume 136, Issue -, Pages -Publisher
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.mehy.2019.109518
Keywords
Posterior Segment Eye Diseases; Sirolimus; Polyol modified liposomes; mTOR inhibitor; Blood retinal barrier
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Funding
- Indian Council of Medical Research, New Delhi, India [ICMR-45/51/2018-NAN-BMS]
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Posterior Segment Eye Diseases (PSED) are the major cause of visual impairment globally that directly affects the patients quality of life, especially in the aging population. Vascular degenerative disorders of posterior eye are the vision threatening disorders, involving inflammation as one of the main pathological mechanisms. Use of current treatment regimens for PSED is significantly limited on account of unique environment of the eye that offers a major barrier to the delivery of efficient drug doses to the posterior segment. Sirolimus, a mTOR inhibitor, acts by inhibiting the T-cell proliferation and the release of inflammatory cytokines, have been widely investigated for its potential role in the treatment of PSED. Clinical application of the sirolimus, however, has been limited due to its poor physico-chemical properties like poor aqueous solubility, low bioavailable, high molecular weight and high instability. Although nanocarriers like liposomes have shown a great promise in shuttling the cargo to the target site for various applications, yet, due to distinct anatomical and physiological barriers of the eye, these conventional liposomes are inefficient to shuttle the cargo to the posterior segment. Therefore, in this hypothesis, we propose to incorporate edge activators (polyol) in the liposomal bilayer thereby to enhance the liposomal fluidity and deformability. Such polyol modified liposomes would successfully penetrate the blood retinal barrier and would efficiently shuttle the sirolimus to the posterior segment of the eye making this a promising strategy for the treatment of PSED.
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