Modulated release from implantable ocular silicone oil tamponade drug reservoirs.

Helen Cauldbeck,Maude Le Hellaye,Victoria R Kearns,Mark Long,Steve P Rannard,Rachel L Williams,Tom O Mcdonald

doi:10.1002/pola.28973

Helen Cauldbeck, Maude Le Hellaye + Show 5 more

Open Access

https://doi.org/10.1002/pola.28973

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Abstract

ABSTRACTComplicated cases of retinal detachment can be treated with silicone oil tamponades. There is the potential for silicone oil tamponades to have adjunctive drug releasing behaviour within the eye, however the lipophilic nature of silicone oil limits the number of drugs that are suitable, and drug release from the hydrophobic reservoir is uncontrolled. Here, a radiometric technique was developed to accurately measure drug solubility in silicone oil and measure release into culture media. All‐trans retinoic acid (atRA), a lipophilic drug known to act as an anti‐proliferative within the eye, was used throughout this work. Chain‐end modification of polydimethylsiloxane with atRA produced a polydimethylsiloxane retinoate (PDMS‐atRA), which was used as an additive to silicone oil to modify the solvent environment within the silicone oil and the distribution coefficient. Blends of PDMS‐atRA and silicone oil containing different concentrations of free atRA were produced. The presence of PDMS‐atRA in silicone oil had a positive effect on atRA solubility and the longevity of release in vitro. The drug release period was independent of atRA starting concentration and dependent on the PDMS‐atRA concentration in the blend. A clinically relevant release period of atRA over 7 weeks from a silicone oil blend with PDMS‐atRA was observed. © 2018 The Authors. Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 938–946

Highlights

Retinal detachment (RD) is a potentially blinding condition which has become one of the most common ophthalmic emergencies in the developed world.[1]
In previously published work,[34] we have described the challenges associated with the development of silicone oil tamponade drug delivery reservoirs, and presented a novel polymeric additive to alter the release kinetics of acid functional drugs
Extraction separates the substance of interest from a mixture, this involves the use of two immiscible solvents; the desired compound in suspension in one solvent is extracted into the other solvent

Summary

Introduction

Retinal detachment (RD) is a potentially blinding condition which has become one of the most common ophthalmic emergencies in the developed world.[1]. Saturated solutions of atRA in either SIO1000 or blends of SIO1000 with PDMS-atRA were prepared using a mixture of drug and tritiated drug, and analysed using the radiometric method described previously.

Results

Conclusion