AbstractAbsorption and distribution of any new drug candidate remain imperative components in the drug development process. For more than four decades, researchers have actively embarked on finding alternative ways to replace the use of human skin samples for in-vitro measurement of model drug absorption profiles. More recently, the use of polymeric materials has gained wide consideration as a viable alternative, largely due to physicochemical semblance that can be drawn from some of these polymeric membranes in comparison with the skin. However, an empirical resolve, strong enough to replicate surface activity of the skin, in terms of permeation data is yet to be achieved, which then necessitates the need to look for further approaches.
In this study, one of the polymer membranes widely considered as a potential skin mimic namely, poly(dimethylsiloxane) PDMS was studied and consequently, was chemically modified in an attempt to address some of the many constraints associated with the use of human skin samples.
In the first phase of the study, PDMS membrane was plasma treated using an atmospheric pressure non-thermal air plasma technique; structurally, this process replaces surface methyl groups present on the membrane surface with hydroxyl groups, thereby making the surface of the membrane susceptible for chemical treatments and grafting. This process was followed by silanisation processes using various active saline reagents such as dimethylphenylsilanol, tertbutyldimethylphenylsilanol, pentan-1,5-diol to mention but a few. A modified form of the membrane was characterised with a range of relevant analytical techniques such as scanning electron microscopy (SEM), water contact angle (WCA) analysis, Brunauer-Emmett-Teller (BET) technique and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). Comparative permeation analysis was carried out between standard PDMS membrane and modified forms of the membrane, and drug permeation profiles were quantified using ultraviolet-visible spectroscopy (UV-vis) and high-performance liquid chromatography (HPLC) techniques.
As part of this research work, the concept of ‘smart polymers’ was also studied. Poly(dimethylsiloxane)-poly(ethylene oxide) block co-polymer (PEG-BCP) was identified and grafted onto plasma-treated PDMS membrane. The resultant membrane formed was able to smartly re-orient itself and selectively respond to changes based on sample drug hydrophilicity.
Overall, over-estimation of percutaneous absorption (which is a lingering constraint experienced with the use of polymeric membranes in permeation analysis) was remarkably reduced and reported difficulties experienced with analysing hydrophilic drugs, such as caffeine, were also addressed. Structural integrity, activity and selectivity of the membrane was also improved following modification processes reported herein.
|Date of Award||2023|
|Supervisor||Laura Waters (Main Supervisor) & Gareth Parkes (Co-Supervisor)|