Topical delivery of ocular therapeutics: carrier systems and physical methods

Souza, J. C.; Dias, Karina; Pereira, Tatiana Aparecida; Bernardi, Daniela Spuri; Lopez, Renata Fonseca Vianna

doi:10.1111/jphp.12132

Cited by 113 publications

(79 citation statements)

References 266 publications

(746 reference statements)

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“…11,[13][14][15][16][17][18] While topical administration of drug is the preferred method of delivery for most ocular diseases, including glaucoma, this route is very inefficient. 7,49 In fact, less than 5% of drug applied topically reaches its target tissue within the eye, which necessitates the frequent dosing (up to 3 times daily) required for most topical ocular drugs. 50,[59][60][61] Many factors, including ocular anatomy, blinking, and tear film, limit the bioavailability of topical ocular drugs.…”

Section: Discussionmentioning

confidence: 99%

“…52 Due to these challenges, more efficient drug delivery systems are being developed for ocular tissues that include ocular inserts, lipid-based nanocarriers, nanoparticles, and punctum inserts. 24,[49][50][51][52][53][54] Recent studies using topically applied nanoparticles loaded with ocular hypotensive drugs have shown promise. For example, topical administration of nanoparticles (256 nm) containing the carbonic anhydrase inhibitor methazolamide lowered IOP for 18 hours, with the maximal effect observed 2 to 8 hours after dosing.…”

Section: Discussionmentioning

confidence: 99%

“…Although more studies using our NS are required, we do feel the data presented here add to the growing body of work examining more effective ocular drug delivery methods for the treatment of diseases, like glaucoma and AMD. 24,[49][50][51][52][53][54] Compared to noncompliant patients, patients who adhere to treatment plans have lower ocular pressures, less disc cupping, and less visual field loss over time. 13 Given that glaucoma progresses to blindness, and this progression occurs faster with no treatment, one would think adherence rates for glaucoma therapy would be quite high.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Nanosponge-Mediated Drug Delivery Lowers Intraocular Pressure

Lambert

Carlson

Ende

et al. 2015

Trans. Vis. Sci. Tech.

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Purpose: We examined the efficacy of an extended-release drug delivery system, nanosponge (NS) encapsulated compounds, administered intravitreally to lower intraocular pressure (IOP) in mice.Methods: Bilateral ocular hypertension was induced in mice by injecting microbeads into the anterior chamber. Hypertensive mice received NS loaded with ocular hypotensive drugs via intravitreal injection and IOP was monitored. Retinal deposition and retinal ganglion cell (RGC) uptake of Neuro-DiO were examined following intravitreal injection of Neuro-DiO-NS using confocal microscopy.Results: Brimonidine-loaded NS lowered IOP 12% to 30% for up to 6 days (P , 0.02), whereas travoprost-NS lowered IOP 19% to 29% for up to 4 days (P , 0.02) compared to saline injection. Three bimatoprost NS were tested: a 400-nm NS and two 700-nm NS with amorphous (A-NS) or amorphous/crystalline (AC-NS) crosslinkers. A single injection of 400 nm NS lowered IOP 24% to 33% for up to 17 days compared to saline, while A-NS and AC-NS lowered IOP 22% to 32% and 18% to 26%, respectively, for up to 32 days (P , 0.046). Over time retinal deposition of Neuro-DiO increased from 19% to 71%; Neuro-DiO released from NS was internalized by RGCs.Conclusions: A single injection of NS can effectively deliver ocular hypotensive drugs in a linear and continuous manner for up to 32 days. Also, NS may be effective at targeting RGCs, the neurons that degenerate in glaucoma.Translational Relevance: Patient compliance is a major issue in glaucoma. The use of NS to deliver a controlled, sustained release of therapeutics could drastically reduce the number of patients that progress to vision loss in this disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Nanosponge-Mediated Drug Delivery Lowers Intraocular Pressure

Lambert

Carlson

Ende

et al. 2015

Trans. Vis. Sci. Tech.

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“…The strategies that have been employed to increase drug bioavailability can be broadly divided into those that enhance drug penetration and those that provide sustained-release drug delivery, and are summarized in Table 2, modified from the recent paper by Souza et al 81 and are discussed below.…”

Section: Means Of Enhancing Drug Delivery To the Retinamentioning

confidence: 99%

Recent Advances in Topical Therapeutics for Vitreoretinal Diseases

Gibson¹,

McGinnigle

2015

US Ophthalmic Review

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Amongst other attributes, the ideal drug for retinal disorders should be easy to administer, safe, have a long duration of action, and be costeffective. Needless to say, to date, no such drug exists as far as we are aware, but how close does topical delivery come to meeting these aspirations? Compared with intravitreal drug delivery, topical delivery has some obvious advantages and disadvantages and these are summarized in Table 1.Maurice wrote a seminal review of this subject in 2002, in which he was particularly interested in the passage of drugs delivered by eye AbstractEye drops are convenient for patients, but achieving therapeutic doses and maintaining sustained drug release without frequent re-application to treat diseases of the retina has been largely unsuccessful. Topical administration of drugs is hindered by the anatomy, physiology, and biochemistry of the eye and its highly effective defence mechanisms. Advances in nanotechnology have led to the experimental use of topical permeation-enhancing liposomes, emulsions, and microspheres to enhance absorption and penetration of drugs across membranes; allow controlled release of the drug; and to target drugs at distinct tissues to allow sufficient local bioavailability. In the near future it is hoped that improved technologies may provide means of sustained topical drug delivery for retinal therapy, with improved side-effect profiles and reduced cost compared with currently available clinical treatments.

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“…One includes chemical approaches such as the use of prodrugs, liposomes, cyclodextrins, and chemical enhancers, while others include physical approaches such as iontophoresis (IP) and sonophoresis. 3,4) IP is known as an useful technique to increase the penetration of ionic and non-ionic compounds into the body across surface epithelial tissues including skin and the ocular surface. 5,6) This technique has a potential to regulate the drug delivery depending upon the applied current density and application time and, thus, provides an ON/OFF control.…”

mentioning

confidence: 99%

Characterization of Ocular Iontophoretic Drug Transport of Ionic and Non-ionic Compounds in Isolated Rabbit Cornea and Conjunctiva

Sekijima

Ehara

Hanabata

et al. 2016

Biological & Pharmaceutical Bulletin

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Ocular iontophoresis (IP) in isolated rabbit cornea and conjunctiva was examined in terms of transport enhancement, tissue viability and integrity using electrophysiological parameters by the Ussing-type chamber technique. Lidocaine hydrochloride (LC, a cationic compound), sodium benzoate (BA, anionic compound), and fluorescein isothiocyanate labeled dextran (molecular weight 4400 Da, FD-4, hydrophilic large compound) were used as model permeants. Direct electric current was applied at 0.5-5.0 mA/cm 2 for the cornea and 0.5-20 mA/cm 2 for the conjunctiva for 30 min. LC and BA fluxes across the cornea and conjunctiva were significantly increased by the application of electric current up to 2.3-and 2.5-fold and 4.0-and 3.4-fold, respectively, and returned to their baseline level on stopping the current. Furthermore, a much higher increase by IP application was obtained for the FD-4 transport. The increased FD-4 flux in the conjunctiva returned to baseline on stopping the current, whereas the flux in the cornea was sustained at a higher level after stopping the current. The transepithelial electric resistance of the cornea and conjunctiva was lowered by electric current application but fully recovered after stopping the current up to 2.0 mA/cm 2 for the cornea and 10 mA/cm 2 for the conjunctiva, suggesting that the corneal and conjunctival viability and integrity are maintained even after application of these current densities. These results indicate that ocular IP may be a useful non-invasive technique to achieve drug delivery of hydrophilic large molecules into the eyes.Key words ocular drug delivery; physical enhancement; iontophoresis; electric current; cornea; conjunctiva Eye drops are used for treatment of ocular diseases and the drugs applied by the eye drops distribute onto the ocular surface, then penetrate into the eye through the ocular surface tissues such as cornea and conjunctiva.1) In spite of the simple and convenient dosage form of eye drops, elimination and dilution of drugs by turn-over of tear fluid and the low permeability of the surface ocular tissues are major challenges that limit the absorption of an effective amount of drugs into the eyes.2) Thus, approaches to increase drug absorption into the eyes have attracted much attention. One includes chemical approaches such as the use of prodrugs, liposomes, cyclodextrins, and chemical enhancers, while others include physical approaches such as iontophoresis (IP) and sonophoresis. 3,4)IP is known as an useful technique to increase the penetration of ionic and non-ionic compounds into the body across surface epithelial tissues including skin and the ocular surface. 5,6)This technique has a potential to regulate the drug delivery depending upon the applied current density and application time and, thus, provides an ON/OFF control. A number of in vivo ocular IP studies have shown that application of IP increases the drug concentration in the aqueous and vitreous humors compared to instillation with gentamicin, 7-9) vancomycin, 10) tobramycin, 11,12)...

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Topical delivery of ocular therapeutics: carrier systems and physical methods

Cited by 113 publications

References 266 publications

Nanosponge-Mediated Drug Delivery Lowers Intraocular Pressure

Nanosponge-Mediated Drug Delivery Lowers Intraocular Pressure

Recent Advances in Topical Therapeutics for Vitreoretinal Diseases

Characterization of Ocular Iontophoretic Drug Transport of Ionic and Non-ionic Compounds in Isolated Rabbit Cornea and Conjunctiva

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