recent antiglaucomatous drugs delivery

1. Recent advances for anti glaucoma
drugs delivery
Hany Mahmoud, MD, PhD
Lecturer of ophthalmology
Sohag university

2. Ocular Hypotensive Agents
• Prostaglandin (PG) Analogues
• β blockers
• α agonist
• Carbonic Anhydrase (CA) Inhibitors
• Miotics
• Hyperosmolar agents

3. Surprise in topical medical therapy
1 st line
50 % compliance
5% penetration
Due to
Natural barriers

4. Leclercq B, Mejlachowicz D, Behar-Cohen F. Ocular Barriers and Their Influence on Gene
Therapy Products Delivery. Pharmaceutics. 2022 May 6;14(5):998. doi:
10.3390/pharmaceutics14050998. PMID: 35631584; PMCID: PMC9143174.

5. Need for Newer Drug delivery systems
• Reduced dosing frequency
• Improve adherence and increase precorneal contact.
• Ensure proper application of drug
• Increased bioavailability
• Adequate delivery of drug to target site –
neuroprotective drugs
• Decrease systemic side effects
K.D. Patel, L. Barrios Silva, Y. Park, et al., Recent advances in drug delivery systems for
glaucoma treatment, Materials Today Nano, Volume 18,2022,100178

6. Nanotechnology and nanoparticles
A nanoparticle is a small particle that ranges between 1
to 100 nanometers in size. Undetectable by the human
eye, nanoparticles can exhibit significantly different
physical and chemical properties to their larger material
counterparts.
King, Stephen , Jarvie, Helen and Dobson, Peter. "nanoparticle". Encyclopedia Britannica, 8 Jan.
2024, https://www.britannica.com/science/nanoparticle. Accessed 26 January 2024.

7. King, Stephen , Jarvie, Helen and Dobson, Peter. "nanoparticle". Encyclopedia Britannica, 8 Jan.
2024, https://www.britannica.com/science/nanoparticle. Accessed 26 January 2024.

8. Extra ocular drug delivery systems
In situ gel forming
Liquid ----→ viscoelastic gel
Timoptic-XE® (Merck)
Pilopine HS® (Alcon Laboratories)
(Increase contact time )
Wu Y, Liu Y, Li X, Kebebe D,et al. ,Research progress of in-situ gelling ophthalmic drug delivery
system. Asian J Pharm Sci. 2019 Jan;14(1):1-15. doi: 10.1016/j.ajps.2018.04.008. Epub 2018 May
24. PMID: 32104434; PMCID: PMC7032175.

9. SoliDrop
Microsphere formation by PLCGA in the lower
fornix which degrades over one month.
SoliDrop (Otero Therapeutics, Pittsburgh, PA,
U.S.A) Brimonidine Tetrate.
Fedorchak MV, Conner IP, Schuman JS,et al., Long Term Glaucoma Drug Delivery Using a Topically
Retained Gel/Microsphere Eye Drop. Sci Rep. 2017 Aug 17;7(1):8639. doi: 10.1038/s41598-017-
09379-8. PMID: 28819134; PMCID: PMC5561248.

10. DuraSite ISV-215
Polymer based Mucoadhesive .
Pent block polymer. Pilocarpine , bimatoprost.
DuraSite® (InSite Vision, Alameda, CA, U.S.A).
6 months.
Shafiee A, Bowman LM, Hou E, Hosseini K. Ocular pharmacokinetics of bimatoprost formulated in
DuraSite compared to bimatoprost 0.03% ophthalmic solution in pigmented rabbit eyes. Clin
Ophthalmol. 2013;7:1549-56. doi: 10.2147/OPTH.S48766. Epub 2013 Jul 31. PMID: 23940414;
PMCID: PMC3737010.

11. Ocular inserts
Ocular inserts are sterile solid and semisolid formulations that are
placed in the conjunctival sac between the surface of the eye and
the lower eyelid.
Ocular inserts may release a medication by diff usion, osmosis, or
bioerosion.
6 months.
(Helios™) ForSight Vision5 Inc. (Menlo Park, California, U.S.A)
Kumari A, Sharma PK, Garg VK, et l., Ocular inserts - Advancement in therapy of eye diseases. J
Adv Pharm Technol Res. 2010 Jul;1(3):291-6. doi: 10.4103/0110-5558.72419. PMID: 22247860;
PMCID: PMC3255407.

12. Zinah K. Al-Qaysi, Ian G. Beadham,et al.,Sustained release ocular drug delivery systems for
glaucoma therapy, Expert Opinion on Drug Delivery, (2023) 20:7, 905-919, DOI:
10.1080/17425247.2023.2219053

13. Contact lenses
-Soft contact lenses are made of chemically cross-
linked networks of hydrophilic polymers.
-they could be used for delivery of hydrophilic drugs,
such as timolol and dorzolamide, which elute rapidly
from the highly hydrated polymer networks.
-Soft contact lenses are made
from2hydroxyethylmethacrylate (HEMA)
- Medicated contact lenses may provide controlled and
sustained drug delivery.

14. mechanisms
Zhao L, Song J, Du Y,et al., Therapeutic applications of contact lens-based drug delivery systems in
ophthalmic diseases. Drug Deliv. 2023 Dec;30(1):2219419. doi: 10.1080/10717544.2023.2219419.
PMID: 37264930; PMCID: PMC10240982.

15. disadvantages
advantages
example
Type
Less duration
Easy
Cost less
Timolol, Brimonidine,
pilocarpine
Soak and leak
cost
More duration
antioxidant
Timolol , dorzolamide
Vit E loaded
Cost
Thicker lens
duration
latanoprost
Film
Impregnation
variability
duration
Timolol +chitosan
Enzyme triggered
cost
duration
Timolol
Molecular imprinting

16. Topical ophthalmic drug delivery
device (TODDD)
The Topical Ophthalmic Drug Delivery Device (TODDD, Amorphex
Therapeutics) is a flexible, non-erodible topical device
constructed from a soft elastomeric, non-hydrogel material that is
placed in the upper conjunctival fornix
.The TODDD is a large (20 mm length, 8 mm width, and 1 mm
thickness), yet comfortable device that patients can easily insert
and remove.
Upon insertion into the eye (on the conjunctiva/sclera below the
upper eyelid), the drug diff uses continuously from the device
across the conjunctiva and sclera, without changing the shape of
the device.

17. Kagkelaris K, Panayiotakopoulos G, Georgakopoulos CD. Nanotechnology-based formulations
to amplify intraocular bioavailability. Ther Adv Ophthalmol. 2022 Jul
18;14:25158414221112356. doi: 10.1177/25158414221112356. PMID: 35873277; PMCID:
PMC9301101.

19. Advantages
Long duration up to 3 months.
Easy insertion
More beneficial when 2 drugs used
( Travoprost +Timolol)

20. punctual plug delivery system (PPDS)
OTX-TP
• The OTX-TP (Ocular Therapeutix, Bedford, MA, U.S.A)
• a novel sustained-release travoprost delivery system
that made of a rod-shaped, dried polyethylene glycol-
based hydrogel. A punctum plug inserted into the
superior or inferior canaliculus. Embedded in the
punctum plug are poly (lactic acid) microspheres that
contain encapsulated travoprost.

21. Donnenfeld ED, Holland EJ, Solomon KD. Safety and efficacy of nepafenac punctal plug
delivery system in controlling postoperative ocular pain and inflammation after cataract
surgery. J Cataract Refract Surg. 2021 Feb 1;47(2):158-164. doi:
10.1097/j.jcrs.0000000000000414. PMID: 32925651.
disadvantages
advantages
Discomfort
Lacrimation
migration
Long duration
Easy insertion
tolerable

23. Evolute/Latanoprost punctual
plug delivery system (L-PPDS)

24. Intraocular implants
-Intraocular implants could deliver drugs over a
very long period, lasting months to years. They
are well suited to a clinical setting and can
often be injected via a minimally invasive
procedure.
-intrcameral
-subconjunctival
Mostafa M, Al Fatease A, Alany RG, Abdelkader H. Recent Advances of Ocular Drug Delivery
Systems: Prominence of Ocular Implants for Chronic Eye Diseases. Pharmaceutics. 2023;
15(6):1746. https://doi.org/10.3390/pharmaceutics15061746

25. DURYSTA™
DURYSTA™ (Allergan plc, Dublin, Ireland)
Approved 2020
Intracameral
Travoprost with PLGA.
Nouvadour tech.

26. Shirley M. Bimatoprost Implant: First Approval. Drugs Aging. 2020 Jun;37(6):457-462. doi:
10.1007/s40266-020-00769-8. Erratum in: Drugs Aging. 2020 Jul;37(7):549. PMID: 32447639;
PMCID: PMC7303088.

27. ENV515 or travoprost XR
-ENV515/Travoprost XR (Envisia Therapeutics,
Morrisville, NC, U.S.A)
-Printing technology

28. OTX-TIC
-The OTX-TIC (Ocular Therapeutix, Bedford,
MA, U.S.A)
-Bioabsorbable hydrogel.

29. iDose travoprost
-iDose Travoprost (Glaukos, San Clemente, CA,
U.S.A)
-Titanium implant.
-needs removal.
Glance Editorial Team (2023, Dec 15). FDA approves Glaukos' iDose TR intracameral implant.
Glance by Eyes On Eyecare. https://glance.eyesoneyecare.com/stories/2023-12-15/fda-
approves-glaukos-idose-tr-intracameral-implant.

30. DE-117
-Santen Pharmaceuticals.
-Omidenepag isopropyl (DE-117).
-DE-117 is a selective agonist for the
prostaglandin receptor EP2 and can increase
aqueous humor drainage through both the
trabecular and uveoscleral outflow pathways
Matsuo M, Matsuoka Y, Tanito M. Efficacy and Patient Tolerability of Omidenepag
Isopropyl in the Treatment of Glaucoma and Ocular Hypertension. Clin
Ophthalmol. 2022 Apr 26;16:1261-1279. doi: 10.2147/OPTH.S340386. PMID:
35510270; PMCID: PMC9058248.

31. Durasert™ (Latanoprost)
-Durasert™ technology (pSivida Corp., Watertown
MA, U.S.).
-Subconjunctival.
-linear release kinetics.

32. POLAT-001
-The POLAT-001 (Peregrine Ophthalmic
Pte Ltd, Singapore)
-Subconjunctival.
-Nanoliposome.
-affinity to fatty chain of lipid bilayer
Kim JY, Yim HW. Effect of Topical Prostaglandin Analogue Therapy on Central Corneal
Thickness: A Systematic Review. J Clin Med. 2022 Dec 21;12(1):44. doi:
10.3390/jcm12010044. PMID: 36614844; PMCID: PMC9821235.

33. Intraocular delivery
Extra ocular delivery
Zero order kinetics
More duration
bioavailability
Easy application
without surgery
compliance
advantages
Need surgery
Complications of the
surgery
Somme types need
removal
Short duration
Less targeted
disadvantages

34. summery