Self-Assembling Colloidal System for the Ocular Administration of Cyclosporine A

Luschmann, Christoph; Teßmar, Jörg; Schoeberl, Simon; Strau, Olaf; Luschmann, Karl; Goepferich, Achim

doi:10.1097/ico.0b013e3182a7f3bf

Cited by 30 publications

(7 citation statements)

References 23 publications

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“…Di Tommaso et al 32 detected higher cyclosporine amounts in the corneas of rats treated with methoxy poly(ethylene glycol)-hexyl-substituted poly(lactide) micelles (5 mg/mL cyclosporine) (6470 ± 1730 ng drug /g tissue ) in comparison with an oily solution of the drug at the same concentration (580 ± 110 ng drug /g tissue ). Luschmann et al 33 observed in vitro a more efficient cyclosporine penetration into porcine cornea for drug (1 mg/mL) encapsulated in poly-(ethylene glycol)-fatty alcohol ether type based micelles (1557 ± 407 ng drug /g cornea ) compared to Restasis® (545 ± 137 ng drug / g cornea ). More recently, Prosperi-Porta et al 34 developed poly(Llactide)-b-poly(methacrylic acid-co-3-acrylamidophenylboronic acid) block copolymer micelles as mucoadhesive cyclosporine delivery system, while Bonferoni et al 29 demonstrated the enhancing effect of palmitoyl glycol chitosan micelles to promote ex vivo drug penetration in pig cornea.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Several studies have focused on colloidal systems such as solid lipid nanoparticles, , nanostructured lipid carriers, nanoparticles, − liposomes, nanosuspensions, and micelles. − Micelles may be particularly useful for cyclosporine ocular delivery, being able to increase water solubility of poorly soluble drugs without the need for an oily phase, and to enhance permeability across the physiological barriers. − Guo et al demonstrated a significantly more efficient in vivo penetration into rabbit cornea when cyclosporine (0.5 mg/mL) was encapsulated in polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer micelles compared to a cyclosporine oil-based solution of much higher concentration (10 mg/mL). Di Tommaso et al detected higher cyclosporine amounts in the corneas of rats treated with methoxy poly(ethylene glycol)-hexyl-substituted poly(lactide) micelles (5 mg/mL cyclosporine) (6470 ± 1730 ng drug /g tissue ) in comparison with an oily solution of the drug at the same concentration (580 ± 110 ng drug /g tissue ).…”

Section: Introductionmentioning

confidence: 99%

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Poloxamer 407/TPGS Mixed Micelles as Promising Carriers for Cyclosporine Ocular Delivery

et al. 2018

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Cyclosporine is an immunosuppressant agent approved for the treatment of dry eye disease and used off-label for other ocular pathologies. Its formulation and ocular bioavailability present a real challenge due to the large molecular weight (1.2 kDa), high lipophilicity, and low water solubility. The aim of the work was to develop an aqueous micellar formulation for an efficient cyclosporine delivery to the ocular tissues, using a water-soluble derivative of vitamin E (TPGS: d-α-tocopheryl polyethylene glycol 1000 succinate) and poloxamer 407 (Pluronic ®F127) as excipients. The mixed micelles were characterized in terms of particle size, zeta potential, rheology, and stability upon dilution and freeze-drying. Additionally, the enzymatic-triggered release of vitamin E and vitamin E succinate from TPGS was investigated in vitro in the presence of esterase. Compared to the commercially available ophthalmic formulation, the poloxamer 407:TPGS 1:1 molar ratio micellar formulation significantly improved cyclosporine solubility, which increased proportionally to surfactant concentration reaching 0.4% (w/v) for 20 mM surfactant total concentration. Cyclosporine-loaded mixed micelles efficiently retained the drug once diluted in simulated lachrymal fluid and, in the presence of a 20 mM surfactant concentration, were stable upon freeze-drying. The drug-loaded mixed micelles were applied ex vivo on porcine cornea and compared to Ikervis®. Drug accumulation in the cornea resulted proportional to drug concentration (6.4 ± 1.9, 17.6 ± 5.4, and 26.9 ± 7.4 μg/g, after 3 h for 1, 2.5, and 4 mg/mL cyclosporine concentration respectively). The formulation containing cyclosporine 4 mg/mL (20 mM surfactant) was also evaluated on the sclera, with a view to targeting the posterior segment. The results demonstrated the capability of mixed micelles to diffuse into the sclera and sustain cyclosporine delivery (28 ± 7, 38 ± 10, 57 ± 9, 145 ± 27 μg/cm cyclosporine accumulated after 3, 6, 24, and 48 h respectively). Reservoir effect experiments demonstrated that the drug accumulated in the sclera can be slowly released into the underlying tissues. Finally, all the formulations developed in this work successfully passed the HET-CAM assay for the evaluation of ocular irritability.

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Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Poloxamer 407/TPGS Mixed Micelles as Promising Carriers for Cyclosporine Ocular Delivery

et al. 2018

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“…В мире проводятся исследования различных способов пролонгированной доставки циклоспо-рина А, в том числе в составе временных ок-клюдеров слёзных точек, поскольку в ряде работ отмечено повышение эффективности лечения тя-жёлых форм ССГ при сочетании этих двух мето-дов [38,63,91]. Кроме того, при лечении тяжёлых форм ССГ изучается воздействие местных форм такролимуса (современный высокоэффективный иммуносупрессор), перспективы применения ко-торого в офтальмологии представляются очень многообещающими [49].…”

Section: реакция «трансплантат против хозяина»unclassified

Ophthalmic manifestation of leukemia

Chistyakova

Викторовна²

2016

Ophthalmology Reports

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ОфтальмОлОгические ПрОЯвлениЯ леЙкОЗОвG This paper includes a literature review on the ophthalmic manifestations of leukemia. Various eye disorder types in leukemia with concurrent anemia, hypoxia, increased blood viscosity, as well as the compression of tissues by tumor cells conglomerates and/or presence of direct leukemic infiltration were considered. Ophthalmic diseases in patients with hematological malignancies may occur due to opportunistic infections and the impact of such treatments as chemotherapy, radiotherapy and bone marrow transplantation. Reliable estimation of eye involvement rates in leukemic process is difficult, as many patients are asymptomatic at early stages of the disease. However, the predictive value of visual impairment assessment in leukemia is high, which requires close cooperation between ophthalmologists and hematologists, and appropriate adjustment of both local and systemic therapies.G

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“…They have been evaluated for therapeutic agent (drug, gene, and protein) delivery systems, as well as for diagnostic application. Almost all drug administration routes (parenteral, oral, nasal, and ocular) have benefited from micellar forms of drugs in terms of either increased bioavailability or reduction of adverse effects …”

Section: Introductionmentioning

confidence: 99%

Applications of polymer micelles for imaging and drug delivery

Movassaghian

Merkel

Torchilin

2015

WIREs Nanomed Nanobiotechnol

223

141

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Polymeric micelles, self-assembling nano-constructs of amphiphilic copolymers, are widely considered as convenient nano-carriers for a variety of applications, such as diagnostic imaging, and drug and gene delivery. They have demonstrated a variety of favorable properties including biocompatibility, longevity, high stability in vitro and in vivo, capacity to effectively solubilize a variety of poorly soluble drugs, changing the release profile of the incorporated pharmaceutical agents, and the ability to accumulate in the target zone based on the enhanced permeability and retention effect. Moreover, additional functions can be imparted to the micelle-based delivery systems by engineering their surface for specific applications. Various targeting ligands can be attached for cell or intracellular accumulation at a site of interest. Also, the chelation or incorporation of imaging moieties into the micelle structure enables in vivo biodistribution studies. Moreover, pH-, thermo-, ultrasound-, enzyme- and light-sensitive block-copolymers allow for controlled micelle dissociation and triggered drug release in response to the pathological environment-specific stimuli and/or externally applied signals. The combination of these approaches can further improve specificity and efficacy of micelle-based drug delivery to promote the development of smart multifunctional micelles.

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Self-Assembling Colloidal System for the Ocular Administration of Cyclosporine A

Abstract: In conclusion, we have shown a promising simple and efficient approach for the application of CsA in an aqueous solution to the cornea to treat inflammatory corneal diseases.

Cited by 30 publications

References 23 publications

Poloxamer 407/TPGS Mixed Micelles as Promising Carriers for Cyclosporine Ocular Delivery

Poloxamer 407/TPGS Mixed Micelles as Promising Carriers for Cyclosporine Ocular Delivery

Ophthalmic manifestation of leukemia

Applications of polymer micelles for imaging and drug delivery

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