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Drug delivery implants in the treatment of vitreous inflammation.

ABSTRACT: The eye is a model organ for the local delivery of therapeutics. This proves beneficial when treating vitreous inflammation and other ophthalmic pathologies. The chronicity of certain diseases, however, limits the effectiveness of locally administered drugs. To maintain such treatments often requires frequent office visits and can result in increased risk of infection and toxicity to the patient. This paper focuses on the implantable devices and particulate drug delivery systems that are currently being implemented and investigated to overcome these challenges. Implants currently on the market or undergoing clinical trials include those made of nonbiodegradable polymers, containing ganciclovir, fluocinolone acetonide, triamcinolone acetonide, and ranibizumab, and biodegradable polymers, containing dexamethasone, triamcinolone acetonide, and ranibizumab. Investigational intravitreal implants and particulate drug delivery systems, such as nanoparticles, microparticles, and liposomes, are also explored in this review article.

SUBMITTER: Wang J

PROVIDER: S-EPMC3804444 | biostudies-other | 2013

REPOSITORIES: biostudies-other

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Drug delivery implants in the treatment of vitreous inflammation.

Wang Jillian J Jiang Angela A Joshi Malav M Christoforidis John J

Mediators of inflammation 20130928

The eye is a model organ for the local delivery of therapeutics. This proves beneficial when treating vitreous inflammation and other ophthalmic pathologies. The chronicity of certain diseases, however, limits the effectiveness of locally administered drugs. To maintain such treatments often requires frequent office visits and can result in increased risk of infection and toxicity to the patient. This paper focuses on the implantable devices and particulate drug delivery systems that are current ...[more]

PMID: 24191132

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Project description:P-glycoprotein (Pgp), a member of the ATP-binding cassette family, is one of the major causes of multidrug resistance in tumors. Current clinical treatments to overcome MDR involve the co-delivery of a Pgp inhibitor and a chemotherapeutic. A concern for this treatment that has led to varied clinical trial success is the associated systemic toxicities involving endogenous Pgp. Local drug delivery systems, such as in situ forming implants (ISFIs), alleviate this problem by delivering a high concentration of the drug directly to the target site without the associated systemic toxicities. ISFIs are polymeric drug solutions that undergo a phase transition upon injection into an aqueous environment to form a solid drug eluting depot allowing for a high initial intratumoral drug concentration. In this study, we have developed an ISFI capable of overcoming the Pgp resistance by co-delivering a chemotherapeutic, Doxorubicin (Dox), with a Pgp inhibitor, either Pluronic P85 or Valspodar (Val). Studies investigated in vitro cytotoxicity of Dox when combined with either Pgp inhibitor, effect of the inhibitors on release of Dox from implants in PBS, in vivo Dox distribution and retention in a subcutaneous flank colorectal murine tumor, and therapeutic response characterized by tumor growth curves and histopathology. Dox + Val showed a 4-fold reduction in the 50% lethal dose (LD50) after 48?hours. Concurrent delivery of Dox and Val showed the greatest difference at 16 days post injection for both Dox penetration and retention. This treatment group had a 5-fold maximum Dox penetration compared to Dox alone ISFIs (0.53 ± 0.22?cm vs 0.11 ± 0.11?cm, respectively, from the center of the ISFI). Additionally, there was a 3-fold increase in normalized total intratumoral Dox intensity with the Dox + Val ISFIs compared to Dox alone ISFIs (0.54 ± 0.11 vs 0.18 ± 0.09, respectively). Dox + Val ISFIs showed a 2-fold reduction in tumor growth and a 27.69% increase in necrosis 20 days post-injection compared to Dox alone ISFIs. These findings demonstrate that co-delivery of Dox and Val via ISFI can avoid systemic toxicity issues seen with clinical Pgp inhibitors.

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Drug delivery implants in the treatment of vitreous inflammation.

Publications

Drug delivery implants in the treatment of vitreous inflammation.

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