Design and characterisation of an intraocular nanobubble drug delivery system
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Date
2021
Authors
Mokolobate, Kealeboga
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Abstract
The posterior segment of the eye poses many challenges in terms of drug delivery.
Procedures such as intraocular injections are invasive, are associated with low
compliance, and may yield health hazards such as cataracts. This study aimed to design a
layer-by-layer-originated lipopolymeric intraocular nanoparticulate system,
administered in the cul-de-sac of the eye, for the treatment of uveitis. The main aim is for
the formulation to have theranostic capability: the ability to treat the disease, and also
visually track the movement of the nanoparticulate systems through ultrasound the use
of Vevo®2100 high resolution ultrasound imaging system. These nanoparticulate systems
were produced by dissolving the lipids (cholesterol and soybean oil), buffer pH 7.4 and
drug in chloroform. This emulsion was sonicated and the organic solvent was removed.
The emulsion was then freeze-thawed. Following that, a layer of chitosan was added to
the nanoparticles, allowed to deposit, and finally, a layer of polyethene glycol was added
and allowed to deposit. Zetasizing was used conducted to ensure stable particles within
the nanometre range (below 200nm). Drug release studies were conducted on the
formulations and images through atomic force microscopy highlighted nanoparticles
with a thick shell due to the reinforced layering, effectively entrapping the drug. This
study illustrated how the variables (time of sonication, number of freeze-thaw cycles and
amount of polymer [soybean oil) affected the formulation and enabled determination of
an optimised formulation. The chemical stability of the formulations was examined by
Fourier Transform Infrared(FTIR) and X-Ray Crystallography. Differential Scanning
Calorimetry and Thermogravimetric Analysis assessed the formulation’s reaction to heat,
and thus stability. Rheological studies assisted in elucidating rheological behaviour and
likely behaviour in the eye. This formulation (once incorporated into a suspension) will
circumvent the need for invasive procedures regarding infections in the posterior
segment of the eye in treating uveitis
Description
A dissertation submitted in fulfilment of the requirements for the degree of Master of Science in Medicine (Pharmaceutical Affairs) to the Faculty of Health Sciences, School of Therapeutic Sciences, University of the Witwatersrand, Johannesburg, 2021