Corneal Permeation Studies of Everolimus Microemulsion

Baspinar, Yuecel; Bertelmann, Eckart; Pleyer, Uwe; Buech, Guido; Siebenbrodt, Ingo; Borchert, Hans-Hubert

doi:10.1089/jop.2007.0088

Cited by 27 publications

(11 citation statements)

References 16 publications

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“…In addition, this method has been shown to achieve drug concentrations of up to 8.64 and 15.95 ng/mL in the cornea after 0.5 and 4 h, respectively. 13 Ethosomes, a type of carrier molecule, have many advantages for the treatment of eye irritation, including high stability; however, very few types are available for clinical application, and high concentrations can be toxic. 14,15 Cyclodextrin has been widely studied as a carrier in ophthalmic drug delivery systems and has been shown to prolong ocular retention time and increase drug solubility and bioavailability, thereby improving the drug's effectiveness.…”

Section: Introductionmentioning

confidence: 99%

Corneal permeation properties of a charged lipid nanoparticle carrier containing dexamethasone

Ban¹,

Zhang²,

Huang³

et al. 2017

IJN

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Drug delivery carriers can maintain effective therapeutic concentrations in the eye. To this end, we developed lipid nanoparticles (L/NPs) in which the surface was modified with positively charged chitosan, which engaged in hydrogen bonding with the phospholipid membrane. We evaluated in vitro corneal permeability and release characteristics, ocular irritation, and drug dynamics of modified and unmodified L/NPs in aqueous humor. The size of L/NPs was uniform and showed a narrow distribution. Corneal permeation was altered by the presence of chitosan and was dependent on particle size; the apparent permeability coefficient of dexamethasone increased by 2.7 and 1.8 times for chitosan-modified and unmodified L/NPs, respectively. In conclusion, a chitosan-modified system could be a promising method for increasing the ocular bioavailability of unmodified L/NPs by enhancing their retention time and permeation into the cornea. These findings provide a theoretical basis for the development of effective drug delivery systems in the treatment of ocular disease.

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Section: Introductionmentioning

confidence: 99%

Corneal permeation properties of a charged lipid nanoparticle carrier containing dexamethasone

Ban¹,

Zhang²,

Huang³

et al. 2017

IJN

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“…Therefore, various oral formulations, such as inclusion complexes [10,11], liposomes [12], nanocrystals [13], and solid dispersion [14] have been developed and tested in pre-clinical and clinical studies. In this study, we tested the biological activity of a novel formulation of rapamycin, Rapatar.…”

Section: Introductionmentioning

confidence: 99%

New nanoformulation of rapamycin Rapatar extends lifespan in homozygous p53−/− mice by delaying carcinogenesis

Comas

Toshkov²,

Kuropatwinski³

et al. 2012

Aging

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The nutrient-sensing mTOR (mammalian Target of Rapamycin) pathway regulates cellular metabolism, growth functions, and proliferation and is involved in age-related diseases including cancer, type 2 diabetes, neurodegeneration and cardiovascular disease. The inhibition of mTOR by rapamycin, or calorie restriction, has been shown to extend lifespan and delays tumorigenesis in several experimental models suggesting that rapamycin may be used for cancer prevention. This requires continuous long-term treatment making oral formulations the preferred choice of administration route. However, rapamycin by itself has very poor water solubility and low absorption rate. Here we describe pharmacokinetic and biological properties of novel nanoformulated micelles of rapamycin, Rapatar. Micelles of Rapatar were rationally designed to increase water solubility of rapamycin to facilitate oral administration and to enhance its absorption. As a result, bioavailability of Rapatar was significantly increased (up to 12%) compared to unformulated rapamycin, which concentration in the blood following oral administration remained below level of detection. We also demonstrated that the new formulation does not induce toxicity during lifetime administration. Most importantly, Rapatar extended the mean lifespan by 30% and delayed tumor development in highly tumor-prone p53−/− mice. Our data demonstrate that water soluble Rapatar micelles represent safe, convenient and efficient form of rapamycin suitable for a long-term treatment and that Rapatar may be considered for tumor prevention.

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“…Hence, o/w‐based microemulsions are widely used for the delivery of hydrophobic drugs across ocular tissues (Leonardi et al, ). Due to the small size and large surface area of the dispersed droplets, microemulsions have been demonstrated to exhibit a better interaction with ocular tissues and as a consequence improve permeation, retention, and bioavailability of topically administered medicaments (Baspinar et al, ; M. A. Kalam, Alshamsan, Aljuffali, Mishra, & Sultana, ; Vandamme, ). In a study, M. A. Kalam et al () demonstrated that topically administered microemulsion‐based delivery system improved ocular permeation and retention of gatifloxacin, and as a consequence, improved the bioavailability by up to twofold in aqueous humor of rabbit eyes when compared to solution‐based systems.…”

Section: Ocular Drug Delivery Systemsmentioning

confidence: 99%

Fundamentals, challenges, and nanomedicine‐based solutions for ocular diseases

Srinivasarao

Lohiya

Katti

2018

WIREs Nanomed Nanobiotechnol

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The eye consists of sensitive, compactly adjoined tissue structures which act as strong physical (static) and physiological (dynamic) barriers that prevent entry of foreign bodies into the eye. Together, these barriers reduce the bioavailability of topically and intraocularly administered medicaments thus demanding frequent drug administration for the treatment of chronic eye diseases. Hence, development of drug delivery systems (DDS) that can be retained in ocular tissues for longer durations can help to reduce the frequency of drug administration, whereas, delivery systems that traverse through ocular barriers may offer higher bioavailability of administered drugs to otherwise inaccessible ocular tissues. These objectives can be partially/fully achieved using nanoparticulate/colloidal DDS. Colloidal DDS, due to their nanodimensions, undergo internalization by cells which enables transport of drugs through ocular barriers. Furthermore, nanoparticles can prolong duration of drug release and can increase residence time of entrapped cargo molecules in ocular tissues. Together, these aspects facilitate a higher bioavailability, prolonged therapeutic effect and reduced frequency of drug administration for the effective treatment of chronic ocular diseases. Hence, nanocarriers have been widely explored for ophthalmic drug delivery applications. In this review, we discuss the anatomy of ocular tissues along with their barrier properties. We then discuss ocular diseases along with the various routes of drug administration and pathways of drug transport in the eye. The next section discusses the influence of physicochemical properties of therapeutic molecules on their ocular distribution and conventional and advanced (nanoparticulate/colloidal DDS) drug formulations that are used for the treatment of ocular diseases.

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Corneal Permeation Studies of Everolimus Microemulsion

Abstract: This everolimus-containing microemulsion is a promising ocular formulation for preventing corneal-graft rejection.

Cited by 27 publications

References 16 publications

Corneal permeation properties of a charged lipid nanoparticle carrier containing dexamethasone

Corneal permeation properties of a charged lipid nanoparticle carrier containing dexamethasone

New nanoformulation of rapamycin Rapatar extends lifespan in homozygous p53−/− mice by delaying carcinogenesis

Fundamentals, challenges, and nanomedicine‐based solutions for ocular diseases

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