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Peer-reviewed articles

2022

Desai,D. T., Maulvi,F. A., Desai,A. R., Shukla,M. R., Desai,B. V., Khadela,A. D., Shetty,K. H., Shah,D. O., Willcox,M. D. P. In vitro and in vivo evaluation of cyclosporine-graphene oxide laden hydrogel contact lenses International Journal of Pharmaceutics 2022;613121414 [ Show Abstract ]

Drug-eluting contact lens can substitute the multiple eye drop therapy. However, loading hydrophobic drug like cyclosporine in the contact lens is very challenging, due to low drug uptake (via soaking method); and alteration in the swelling and optical properties which restricts its clinical application. To address the above issues, graphene oxide (GO, large surface area with oxygen containing functional groups) was incorporated in the contact lenses during fabrication. These GO-laden contact lenses (SM-GO-Cys) as well as blank contact lenses (SM-Cys) were soaked in the solution of cyclosporine. Alternatively, cyclosporine-laden contact lenses (DL-Cys-20) and cyclosporine-GO-laden contact lenses (DL-Cys-20-GO) were fabricated by adding drug and drug-GO (at various level of GO) during fabrication, respectively. Contact angle and swelling data showed increase in water holding capacity of GO laden contact lenses. Optical property was significantly improved due to molecular dispersion of drug on the surface of GO sheets. The drug uptake and in vitro release profile was improved with GO-laden contact lenses by soaking method (SM-GO-Cys-400n) due to hydrophobic interactions between GO and drug. Adding cyclosporine-GO (DL-Cys-20-GO-800n) during fabrication significantly improved drug release kinetics with higher drug leaching (during extraction and sterilization) due to increased swelling, improved dissolution and molecular dispersion of drug on GO sheets. Ocular irritation and histopathological studies demonstrated the safety of GO-contact lens. The in vivo drug release studies in the rabbit eye showed significant improvement in mean residence time (MRT) and area under the curve (AUC) using DL-Cys-20-GO-800n contact lens compared to eye drop solution with reduction in protein adherence value. The study demonstrated that the incorporation of GO into the contact lens can control the release of cyclosporine as well as improved the lens swelling and transmittance properties.

Lourenco Nogueira,C., Boegel,S. C., Shukla,M., Ngo,W., Jones,L., Aucoin,M. G. Antiviral Activity of Contemporary Contact Lens Care Solutions against Two Human Seasonal Coronavirus Strains Pathogens 2022;11(4):472 [ Show Abstract ]

Background: Given that reports have suggested SARS-CoV-2 can be transmitted via conjunctiva, the ability of contact lens (CL) care products to reduce the infectiousness of two seasonal human coronavirus (HCoV) (HCoV-229E and HCoV-OC43) surrogates for SARS-CoV-2 was investigated.

Methods: Biotrue and Boston Simplus (Bausch&Lomb), OPTI-FREE Puremoist and Clear Care (Alcon), and cleadew and cleadew GP (Ophtecs) were tested. Their ability to inactivate HCoV was evaluated using contact times of 4 and 6 h as well as 1% and 10% of virus inoculum.

Results: Non-oxidative systems (Biotrue, Boston Simplus, and OPTI-FREE) did not exhibit a significant log10 reduction compared to controls for the two viral strains for either incubation time (all p > 0.05) when 10% tests were performed. For the 1% test, while Boston Simplus and OPTI-FREE exhibited a significant log10 reduction of both HCoV-229E (after 6 h) and HCoV-OC43 (after either 4 or 6 h incubation), those products showed less than 1 log10 reduction of the two infectious viruses. Oxidative systems based on hydrogen peroxide or povidone-iodine showed a significant log10 reduction compared with the controls for both HCoV-229E and HCoV-OC43 in all tested conditions (all p < 0.01). Clear Care led to virus inactivation to below the limit of quantification for tests performed with 1% of inoculum after 6 h incubation, while cleadew and cleadew GP led to inactivation of the two viruses to below the limit of quantification in all tested conditions.

Conclusion: Oxidative CL disinfection systems showed significant virucidal activity against HCoV-229E and HCoV-OC43, while non-oxidative systems showed minimal ability to inactivate the HCoV species examined.

Lourenco Nogueira,C., Boegel,S. C., Shukla,M., Ngo,W., Jones,L. Aucoin,M. G. The impact of a rub and rinse regimen on removal of human coronaviruses from contemporary contact lens materials Contact Lens Anterior Eye 2022;45(6):101719 [ Show Abstract ]

Purpose
To assess the influence of contemporary contact lens (CL) materials on human coronavirus attachment and the influence of a rub and rinse step to remove these viruses.

Methods
The binding rates of HCoV-229E and HCoV-OC43 to eight soft CL materials and four rigid gas permeable materials were analyzed. The impact of a rub and rinse step to remove these viruses from all materials was examined. The efficacy of Biotrue (Bausch & Lomb), OPTI-FREE Puremoist (Alcon), Clear Care (Alcon) and cleadew (Ophtecs) to remove virus contamination from two representative soft lens materials (etafilcon A and lotrafilcon B) was also determined.

Results
Approximately 102 to 103 infectious viral particles were recovered from each CL material. Although some materials were more prone to coronavirus adhesion, contamination of both viral types was reduced to below the limit of quantification (LQ) from all materials using a simple saline rinse step. Exposure to Clear Care and cleadew reduced the number of infectious viral particles from both etafilcon A and lotrafilcon B to below the LQ, while for Biotrue and OPTI-FREE Puremoist, infectious viral particles were reduced to below the LQ only when additional rub and rinse steps were included.

Conclusion
Human coronavirus contamination can be easily removed from CL surfaces. Although CL care products containing hydrogen peroxide and povidone-iodine efficiently removed virus contamination from CL surfaces without the need for a rub and rinse step, a full regimen including rub and rinse steps is crucial when using CL care products based on non-oxidative systems.

2021

Phan,C. M., Shukla,M., Walther,H., Heynen,M., Suh,D., Jones,L. Development of an In Vitro Blink Model for Ophthalmic Drug Delivery Pharmaceutics 2021;13(Article 300):1-10 [ Show Abstract ]

Purpose: The purpose of this study was to develop an advanced in vitro blink model that
can be used to examine the release of a wide variety of components (for example, topical ophthalmic
drugs, comfort-inducing agents) from soft contact lenses. Methods: The model was designed using
computer-aided design software and printed using a stereolithography 3D printer. The eyelid and
eyeball were synthesized from polyvinyl alcohol and silicone material, respectively. Simulated
tear fluid was infused through tubing attached to the eyelid using a syringe pump. With each
blink cycle, the eyelid slides and flexes across the eyeball to create an artificial tear film layer. The
flow-through fluid was collected using a specialized trough. Two contact lenses, etafilcon A and
senofilcon A, were incubated in 2 mL of a water-soluble red dye for 24 h and then placed on the eye
model (n = 3). The release of the dye was measured over 24 h using a tear flow rate of 5 µL/min.
Results: Approximately 25% of the fluid that flowed over the eye model was lost due to evaporation,
nonspecific absorption, and residual dead volume. Senofilcon A absorbed more dye (47.6 ± 2.7 µL)
than etafilcon A (22.3 ± 2.0 µL). For etafilcon A, the release of the dye followed a burst-plateau
profile in the vial but was sustained in the eye model. For senofilcon A, the release of the dye was
sustained in both the vial and the eye model, though more dye was released in the vial (p < 0.05).
Overall, the release of the dye from the contact lenses was higher in the vial compared with the eye
model (p < 0.05). Conclusion: The blink model developed in this study could be used to measure
the release of topical ophthalmic drugs or comfort agents from contact lenses. Simulation of a blink
mechanism, an artificial tear film, and nonspecific absorption in an eye model may provide better
results than a simple, static vial incubation model.

2020

Desai,A. R., Maulvi,F. A., Desai,D. M., Shukla,M. R., Ranch,K. M., Vyas,B. A., Shah,S. A., Sandeman,S., Shah,D. O. Multiple drug delivery from the drug-implants-laden silicone contact lens: Addressing the issue of burst drug release Materials Science and Engineering: C 2020;112(July):110885 [ Show Abstract ]

A fixed combination of bimatoprost/timolol eye drop solution is used to manage the elevated intra-ocular pressure in glaucoma patients, including individuals whose condition is poorly controlled by monotherapy. Eye drop solutions are generally given in high dose, due to poor ocular bioavailability. The high ocular dose of bimatoprost and timolol lead to hyperaemia and systemic cardiac side effects respectively. Here, we introduce multiple implant-laden contact lenses (IM) to passively deliver timolol, bimatoprost and hyaluronic acid at therapeutically relevant doses without high burst release. The drug-loaded implants were individually implanted in the outer periphery of the silicone contact lenses. Atomic force microscopy showed the smooth surface of the implant contact lens, as the implants were inside the contact lens matrix. The implant lens (IM) showed major loss of drugs [timolol = 60.60%, bimatoprost = 61.75% and HA = 46.03%] during the monomer extraction and wet sterilization, while the option of dry radiation sterilization (IM-R lens) and hydration for 24 h prior to use showed relatively lower loss of drugs [timolol = 16.87%, bimatoprost = 47.95% and HA = 24.41%]. The in-vitro drugs release data of IM-R lens, showed sustained release for 72 h, with low burst release in comparison to the soaked (SM) and direct drug-laden contact lenses (DL). The in vivo drug release data in the rabbit tear fluid showed sustained release using IM-R lens in comparison to the SM lens and eye drop therapy. The burst release with the IM-R lens was many folds reduced, which could bypass the side effects associated with multiple eye drop therapy. The in vivo pharmacodynamic study in the rabbit model showed peak and valley profile with multiple eye drop therapy, while IM-R lens showed prolong reduction in intra ocular pressure (IOP) for 120 h. The study demonstrates the application of implantation technology to deliver multiple drug through contact lenses to treat glaucoma.

Maulvi,F. A., Parmar,R. J., Desai,A. R., Desai,M. D., Shukla,M. R., Ranch,K. M., Shah,S. A., Shah,D. O. Tailored gatifloxacin Pluronic® F-68-loaded contact lens: Addressing the issue of transmittance and swelling. International journal of pharmaceutics International Journal of Pharmaceutics 2020;581(May 15):119279 [ Show Abstract ]

Loading of gatifloxacin in contact lenses affects critical lens properties (optical and swelling) owing to drug precipitation in the contact lens matrix. The presence of Pluronic® F-68 in the packaging solution creates in-situ micelles in the contact lens to dissolve gatifloxacin precipitates and provide sustained drug release. The micelles further improved the drug uptake from the drug-packaging solution to create an equilibrium of drug between the lens matrix and the packaging solution. In this study, we optimized gatifloxacin-pluronic-loaded contact lenses to achieve the desired optical transmittance, swelling, and gatifloxacin loading capacity as well as sustained drug delivery. Optimization of gatifloxacin-pluronic-loaded contact lens was carried out using a 32 factorial design by tailoring the concentration of Pluronic® F-68 in the packaging solution (X1) and the amount of gatifloxacin in the monomer solution (X2) to achieve the desired lens properties. The optimized batch (X1 = 0.3%w/v and X2 = 0.3%w/v) showed an optical transmittance of 92.84%, swelling of 92.36% and gatifloxacin loading capacity of 92.56 μg. The in vitro flux data of the optimized batch (GT-Pl-CL) showed sustained release up to 72 h, whereas soaked contact lenses (SM-CL) and direct gatifloxacin-loaded contact lenses (DL-CL) showed a sustained release up to 48 h. The in vivo gatifloxacin release data for rabbit tear fluid showed sustained release with a high gatifloxacin level for the GT-Pl-CL lens in comparison to the SM-CL and the eye drop solution. This study demonstrates the application of the 32 full factorial design to optimize gatifloxacin-pluronic-loaded contact lenses to achieve the desired optical transmittance, swelling, and drug loading capacity.

Maulvi,F. A., Patel,P. J., Soni,P. D., Desai,A. R., Desai,D. T., Shukla,M. R., Ranch,K. M., Shah,S. A., Shah,D. O. Novel Poly(vinylpyrrolidone)-Coated Silicone Contact Lenses to Improve Tear Volume During Lens Wear: In Vitro and In Vivo Studies ACS Omega 2020;5(29):18148-18154 [ Show Abstract ]

Poly(vinylpyrrolidone) (PVP-K90) is widely used to manage dry eye syndrome (DES). The marketed eye drop solutions (high dose) need frequent instillation, affecting the routine lifestyle of patients. PVP-K90-laden contact lenses can be used to overcome the limitations of eye drop solutions (low bioavailability and frequent instillation). However, the conventional methods of PVP-K90 loading show poor loading capacity and short duration of effect. In the present study, we have developed PVP-K90-coated contact lenses via a short curing approach to increase the PVP-K90 loading capacity with a sustained release profile to manage dry eye syndrome. PVP-K90 was loaded by a soaking method (SM-PVP), direct loading (during fabrication, DL-PVP), a combination of soaking and direct loading (DL-SM-PVP), and a novel coating process (SM-PVP-C and DL-SM-PVP-C). The swelling studies suggested improvement in the water uptake (hydration) property of the contact lenses due to the presence of PVP-K90. The optical transparency was within an acceptable range. The in vitro release of PVP-K90 was in the following order: PVP-coated contact lens (168 h) > DL-SM-PVP (168 h) > DL-PVP (96 h) > SM-PVP (72–96 h). PVP-coated contact lenses showed a high burst effect (lubricating effect) and sustained release (3161–448 ng/h between 24 and 168 h) due to high PVP loading/coating in comparison to the uncoated respective contact lenses (964–113 ng/h between 24 and 96 h). In animal studies, the PVP-K90-coated contact lens showed higher tear volume in comparison to the respective uncoated contact lenses and an eye drop solution. This study demonstrates a novel approach of coating a high amount of PVP-K90 on contact lenses for sustained release to manage several ocular diseases like dry eye syndrome, conjunctivitis, and other ocular injuries.

Scientific Presentations

2022

Shukla M, Phan CM, Jones L. Effect of methacrylic acid on atropine sulfate loading into model contact lens materials 10th Canadian Optometry School Research Conference, Montréal, Canada, Dec 3, 2022

2021

Boegel S, Nogueira C, Shukla M, Ngo W, Jones L, Aucoin M. The impact of a rub and rinse step on the removal of an enveloped virus from a contemporary silicone hydrogel contact lens material American Academy of Optometry, Boston, November, 2021

Nogueira CL, Boegel SC, Shukla M, Ngo W, Jones L, Aucoin MG. Antiviral activity of contemporary contact lens solutions against human seasonal coronavirus strains American Academy of Optometry, Boston, November, 2021

2020

Phan CM, Shukla M, Heynen M, Walther H, Jones L. Development of an In Vitro Blink Model for Measuring Drug and Comfort Agent Elutes from Soft Contact Lens Polymers Academy at Home, 2020 [ Show Abstract ]

Purpose: To develop an advanced in vitro blink model that could be used to examine release of a wide variety of components (topical drugs; comfort agents etc) from soft contact lenses.
Methods: The model was designed using CAD software and 3D printed using an SLA printer. A UV-curable resin polymer was used to fabricate the main components of the eye model to ensure water-sealed parts. The eyelid and eyeball were synthesized from a polyvinyl alcohol and a silicone material respectively. Simulated tear fluid is delivered through tubing attached to the eyelid. With each blink cycle (1 blink/10s), the eyelid slides and flexes across the eyeball to create an artificial tear film. The flow-through fluid is collected in a specialized trough. Two contact lenses, etafilcon A and senofilcon A, were incubated in 2 mL of a water-soluble red dye for 24 hours and then placed on the eye model. The release of the dye was measured at t= 0.5, 1, 2, 4, 8, 12, and 24 hours (n=3) in phosphate buffered saline (flow rate = 5 µL/min). The dye release from the lenses was also evaluated in a vial containing 2 mL of PBS over 24 hours (n=3). The amount of dye in the samples was determined using a UV/Vis spectrophotometer at 520 nm.
Results: All of the contact lenses were visibly red after the incubation with the dye. After the release studies, the etafilcon A lenses became transparent with a slight red tint, whereas the senofilcon A lenses retained a moderate red colour. For the vial study, the release of the dye from the contact lenses was rapid within the first 4 hours, which was then followed by a slower release phase. In contrast, dye release from the lenses on the eye model was significantly slower and was sustained over the 24-hour period. The total amounts of dye released in the eye model were also significantly lower compared to the vial (p<0.05), which could be attributed to the absorption of the dye into the eyelid. From the total amount of tear fluid (7.2 mL) that was infused into the eye model, approximately 5.2 ± 0.6 mL of flow-through was collected. The loss of fluid can be attributed to fluid absorption into the eyelid and contact lenses, as well as evaporation.
Conclusion: The blink model developed in this study could be used to measure the release of topical ophthalmic drugs or comfort agents from contact lenses. The results showed that the release kinetics of a dye from contact lenses on the eye model was significantly different than that of a vial. The model also simulated non-specific absorption of the dye into the eyelid. Future work will focus on developing polymers to simulate the absorption of drugs on the eye.

Continuing Education Presentations

2023

Shukla M. Contact Lenses as a platform for ocular drug delivery Controlled Release Society – Ocular Delivery Focus Group, Webinar, Feb 10, 2023

Books

2021

Ranch KM, Shukla MR, Maulvi FA, Desai DT. Chapter 7: Carbon-based nanoparticles and dendrimers for delivery of combination drugs In: Nanocarriers for the Delivery of Combination Drugs , ed. Baboota S, Ali J. Elsevier Inc.. 2021.