TY - JOUR
T1 - Multiple drug delivery from the drug-implants-laden silicone contact lens
T2 - Addressing the issue of burst drug release
AU - Desai, Ankita
AU - Maulvi, Furqan
AU - Desai, Ditixa
AU - Shukla, Manish
AU - Ranch, Ketan
AU - Vyas, Bhavin
AU - Shah, Shailesh
AU - Sandeman, Susan
AU - Shah, Dinesh
PY - 2020/3/23
Y1 - 2020/3/23
N2 - 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.
AB - 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.
KW - Timolol
KW - bimatoprost
KW - hyaluronic acid
KW - silicone contact lenses
KW - implantation technology
KW - animal studies
KW - Silicone contact lenses
KW - Animal studies
KW - Implantation technology
KW - Hyaluronic acid
KW - Bimatoprost
UR - http://www.scopus.com/inward/record.url?scp=85082921070&partnerID=8YFLogxK
U2 - 10.1016/j.msec.2020.110885
DO - 10.1016/j.msec.2020.110885
M3 - Article
SN - 0928-4931
VL - 112
JO - Materials Science and Engineering: C
JF - Materials Science and Engineering: C
M1 - 110885
ER -