June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Phase inversion-based in situ forming ocular implants for sustained drug delivery
Author Affiliations & Notes
  • Farhan Alshammari
    School of Pharmacy, Queen`s University Belfast, Belfast, Northern Ireland, United Kingdom
  • Ismaiel Tekko
    School of Pharmacy, Queen`s University Belfast, Belfast, Northern Ireland, United Kingdom
  • Ryan Donnelly
    School of Pharmacy, Queen`s University Belfast, Belfast, Northern Ireland, United Kingdom
  • Raghu Raj Singh Thakur
    School of Pharmacy, Queen`s University Belfast, Belfast, Northern Ireland, United Kingdom
  • Footnotes
    Commercial Relationships   Farhan Alshammari, None; Ismaiel Tekko, None; Ryan Donnelly, None; Raghu Raj Singh Thakur, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1955. doi:
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    • Get Citation

      Farhan Alshammari, Ismaiel Tekko, Ryan Donnelly, Raghu Raj Singh Thakur; Phase inversion-based in situ forming ocular implants for sustained drug delivery. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1955.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : This study investigated the feasibility of using phase inversion-based in situ forming implants (PI-ISFI) containing poly (lactic-co-glycolic acid) (PLGA75/25) and N-Methyl-2-pyrrolidone (NMP) for sustained ocular drug delivery.

Methods : PI-ISFI formulations were prepared by dissolving the required amount of different molecular weights (MWs) of FITC-dextran (4, 70, and 150 k Da) in NMP to produce a 0.5% w/w solution before the addition of 30 % w/w of PLGA75/25. PI-ISFI were formed by injecting 50 µL of the gel in 5 mL of phosphate buffer solution (PBS) (pH 7.4 ± 0.2), as a release media. As a result, a solid, spherical implant was formed. Release samples were quantified using fluorescence spectrophotometer. Implants were imaged using scanning electron microscope (SEM) to investigate the microstructure of the implants. Syringeability (work of syringeability (WoS), and maximum force of expulsion (MFE)) was conducted using Texture Analyser. The required force to inject different volumes (10, 25, and 50 µL) of PLGA75/25/NMP (30% w/w) and different PLGA/75/25 concentrations (20%, 30%, and 40% w/w) was evaluated using a 27 G needle. All samples were analyzed in triplicates.

Results : Implant morphology was studied using SEM. The mean thickness of the outer shell of the implants was 819 µm ±16, and a porous structure was observed in all implants. In vitro sustained release of FITC-dextran was achieved over a period of 49 days. However, high burst release was noted in all the formulations irrespective to FITC-dextran’s MW. For example, mean percentage cumulative release of 32.7%, 44.1% and 47.5% was observed on day 1 for FITC-dextran’s of 150, 70, and 4 k Da, respectively. The increase in the MW of FITC-dextran caused a reduction in the percentage of cumulative release. With regards to syringeability, mean WoS values of 53.95 and 132.25 N.mm were observed for injecting 50 µL of 30% w/w and for 40% w/w of PLGA75/25/NMP gel, respectively.

Conclusions : In conclusion, MW of a drug can have a significant impact on drug release from PLGA75/25/NMP PI-ISFI. The release of high MW FITC-dextran (MW 150 k Da) from these implants is slower than low MW FITC-dextran. In addition, the study proves that PLGA75/25/NMP PI-ISFI system has an acceptable syringeability and could provide a sustained drug release over 49 days.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

SEM images of PLGA75/25/NMP (30% w/w) implants loaded with FITC-dextran (a) Mw 4 k Da. (b)Mw 70 k Da. (c)Mw 150 k Da.

SEM images of PLGA75/25/NMP (30% w/w) implants loaded with FITC-dextran (a) Mw 4 k Da. (b)Mw 70 k Da. (c)Mw 150 k Da.

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