Transcript Methods to Assess their Impact and Substantivity

Strategies for Surface Modification:
Methods to Assess their Impact and
Substantivity
Cecile Maissa, Jami Kern, Jessie Lemp
a Novartis company
Silicone hydrogels & Surface Technology approach
• Silicone hydrogel contact lenses
Figure 1. Orientation of hydrophilic sites in a
lens in an aqueous environment
– Greater oxygen transmissibility
– Result in less compromise in anterior
eye physiology
BUT Suffer from poor wettability inherent
to hydrophobic nature
• Soft lenses with a hydrophobic
backbone start out with
hydrophilic sites on the lens
surface
Aqueous
Layer
Hydrophobic
Air Layer
• As the tear film breaks up, the
hydrophilic groups migrate into
the lens producing a hydrophobic,
non wettable surface
2 | ISCLS | Aug 2015 | Confidential - Business Use Only
Hydrophilic
Hydrophobic
Figure 2. Orientation of hydrophilic sites in a dry
environment
XPS Used to Study Adsorption and Retention of HA and EOBO on the Lens Surface
In vitro methods Simulated wear – Substantivity of
Solution Wetting Agent
x 10
2
30
x 10
30
PureVision 2
(neat)
25
Lens only
CPS
CPS
20
15
15
10
10
5
5
290
30
x 10
288
286
284
Binding Energy (eV)
282
280
290
2
30
HA/PureVision 2
25
25
Evidence
of HA
adsorption
15
10
5
5
x 10
30
25
After PBS rinse
CPS
20
288
286
284
Binding Energy (eV)
282
290
x 10
HA/PureVision 2 +
rinse
25
Retention
not evident
20
15
15
286
284
Binding Energy (eV)
282
280
282
280
282
280
Evidence of
EOBO
adsorption
280
2
288
2
EOBO/PureVision 2
15
10
290
x 10
20
CPS
20
CPS
Treated lenses
CPS
The surface activity of HA and
EOBO was evaluated first
through rinsing of the solution
treated lenses. Carbon 1s
binding energy data indicate
that both molecules clearly
adsorb onto the lens surface
from solution. A 3 second rinse
in PBS effectively removes HA
from the surface while EOBO is
observed to persist.
PureVision 2
(neat)
25
20
2
288
286
284
Binding Energy (eV)
2
EOBO/PureVision 2 +
rinse
Retention
evident
10
10
5
5
3 | ISCLS | Aug 2015 | Confidential - Business Use Only
290
288
286
284
Binding Energy (eV)
282
280
290
288
286
284
Binding Energy (eV)
In vitro methods Simulated wear – Substantivity of Solution
Wetting Agent _ Lubricity
Surface Modification of Silicone Hydrogels
through Solution Treatment
Neat PureVision lens
(Alexander R, MRS 2013 Presentation)
EOBO treated PureVision lens –
8 hours simulated wear
Neat PureVision lens
• The effectiveness of the EOBO and HA solution-treated lenses
(PureVision) was further evaluated through simulated wear
accomplished through agitation at 32 Hz in a PBS/hydrogel slurry.
• 5 min shaking time has been correlated (energetically) to 8 hours of
wear, assuming a shear stress of 2.75 kPa and the input of 51 mJ per
interaction.
4 | ISCLS | Aug 2015 | Confidential - Business Use Only
HA treated PureVision lens –
8 hours simulated wear
In vitro methods Simulated wear – Substantivity of Solution
Wetting Agent _ Wettability
Less wettable

Contact Angle measurements of hydrogen peroxide
solution treated lenses conducted after 10 saline/air
cycles to determine substantivity

The 3% hydrogen peroxide contact lens cleaning and
disinfecting solution, containing the HydraGlyde
wetting agent (EOBO-21) provides superior wetting
substantivity.
More wettable
Contact angles of Acuvue® Oasys® lenses pretreated in AOSept® Plus with HydraGlyde® and with
EasySept® Hydro+ after saline/air cycles 0, 3, 5, & 10
5 | ISCLS | Aug 2015 | Confidential - Business Use Only
Contact angles of Acuvue® Oasys® lenses pre-treated in
each marketed peroxide solution after 10 saline/air cycles
In vitro methods – Characterization of Surface technologies



% atomic concentration in silicon measured by XPS
delefilcon A and lotrafilcon A and B exhibiting the lowest
silicon contents within the outermost 1.0 nm of the lens
surface.
Silicon has hydrophobic properties which, when found at the surface,
may influence the wettability of the contact lenses and their
interaction with the tear film and ocular tissues.
Lipidic dye
stains exposed
hydrophobic
domains
6 | ISCLS | Aug 2015 | Confidential - Business Use Only
In vitro methods - Characterization of water gradient
Efficacy
Water gradient
1
AFM (BCLA 2013)1
Sibichen Thekveli, PhD*; Erich Bauman, OD, MBA, FAAO (Alcon Laboratories Inc.)
 The water gradient properties of the delefilcon A
(DAILIES® TOTAL1®) contact lens was assessed
and compared with several other commercially
available silicone hydrogel daily disposable contact
lenses.
 Atomic force microscopy (AFM) data from height,
modulus and tip interaction force channels were
used to elucidate the micro-structure and
morphology of the surface region.
 It was established that delefilcon A lenses contain a
gradient chemical composition, modulus, and water
gradient content from the core to the surface of the
lens.
7 | ISCLS | Aug 2015 | Confidential - Business Use Only
In vitro methods simulated wear – Maintenance of water gradient
Substantivity
Wear models (beads)
Urueña JM ARVO 2013 & 2014 2,3
 Scalable laboratory method to mechanically exercise contact
lenses and simulate wear was established (Urueña 2013).
Energy imparted to the lenses can be tuned and its effects on
lubricity measured as a function of simulated wear time.
 Two hours of agitation delivered mechanical energy can
simulate up to 3 to 5 weeks of blinking.
 Lower driving frequencies resulted in no loss of lubricity, with
a coefficient of friction, µ < 0.02.
 Water gradient maintained during wear
2. Urueña JM, et al., “Laboratory Model for Wear of Contact Lenses and Effects on Lens
Lubricity of Surface Gel Layers”. ARVO 2013. Poster presentation.
3. Urueña JM, Nixon RM, Dunn AC, Sawyer WG, Angelini TE . In vitro mechanical wear of
Contact Lens Surface Gel layers. ARVO 2014. Poster presentation.
8 | ISCLS | Aug 2015 | Confidential - Business Use Only
Ex vivo assessment – Maintenance of lubricity
 Significant association between Coefficient of
friction and comfort ratings
 CoF measured after 16 hours of lens wear
using the incline plane
 The lubricity of delefilcon A water gradient
contact lenses measured after 16 hours of
wear was unchanged compared to unworn
lenses
5. Kern JR, et al. Poster presented at: BCLA Conference; June 6–9, 2014; Birmingham, United Kingdom
9 | ISCLS | Aug 2015 | Confidential - Business Use Only
Strategies for Surface Modification: Methods to Assess their
Impact and Substantivity
In Vitro Out of pack
Friction – AFM
Compositional analysis, Wettability-Contact Angle
In Vitro Simulated wear
Cycling, blink cell models, wear models, Dynamic
Relative Surface
Dehydration
Ex-vivo measurements
Friction, contact angle, lipidomic, proteomic
10 | ISCLS | Aug 2015 | Confidential - Business Use Only
In vitro
out of
pack
In Vitro
simulated
wear
Ex-vivo
Predict
On eye
Conclusion
• In vitro techniques can be used to characterize lens surfaces, confirm
intended surface modifications, and determine the effect of surface
modification on improving key performance measures (e.g. wettability and
lubricity)
• In vitro simulated wear models and ex-vivo methods can be used to confirm
substantivity/maintenance of such modifications over time or with wear
• Both help to better predict the performance of these surface technologies on
eye BUT no substitute for on-eye evaluation
• Future directions:
– Correlating these in vitro/ex vivo performance metrics with patient experience
– Measuring performance on-eye using specialised clinical assessments
11 | ISCLS | Aug 2015 | Confidential - Business Use Only
a Novartis company
12 | ISCLS | Aug 2015 | Confidential - Business Use Only