Sustained-release Formulation of Mitomycin C to the Upper Urinary Tract Using a Thermosensitive Polymer: A
Nicholas M Donin1, Sandra Duarte2, Andrew T Lenis1
1Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
Urology
|October 11, 2016
Summary
MitoGel, a sustained release mitomycin C (MMC) formulation, demonstrated safety and feasibility for upper urinary tract delivery in a preclinical swine model. Further clinical trials are recommended for upper tract urothelial carcinoma treatment.
Area of Science:
- Urology
- Oncology
- Biomedical Engineering
Background:
- Upper tract urothelial carcinoma (UTUC) is a rare malignancy.
- Current treatments for UTUC can be invasive and may lead to nephrectomy.
- Sustained release drug delivery systems offer potential for targeted therapy.
Purpose of the Study:
- To assess the safety and feasibility of delivering MitoGel, a novel sustained release mitomycin C (MMC) formulation, into the upper urinary tract.
- To evaluate MitoGel's performance in a preclinical swine model for potential UTUC treatment.
Main Methods:
- A 3-phase study in 23 pigs utilized bilateral nephrostomy tubes for antegrade instillation.
- Evaluated single and serial (6 instillations over 3 weeks) administrations of MitoGel (2 and 4 mg/mL) and aqueous MMC.
- Included imaging, pharmacokinetic assessment (MMC plasma levels), and histological analysis.
Main Results:
- MitoGel was visible in the pelvicalyceal system for 4-6 hours post-instillation.
- Mitomycin C plasma levels remained within safe thresholds.
- No significant adverse events like urinary obstruction, kidney injury, sepsis, or myelosuppression were observed; histological changes were mild and transient.
Conclusions:
- Antegrade delivery of MitoGel to the swine pelvicalyceal system is feasible and safe.
- MitoGel shows promise as a targeted therapy for UTUC.
- Further investigation in human clinical trials is warranted.
More Related Videos
Related Concept Videos
01:19Modified-Release Drug Delivery Systems: Rate-Programmed II
68
Rate-programmed drug delivery systems release drugs in a controlled manner to maintain therapeutic levels. Three main designs include reservoir, matrix, and hybrid systems.Reservoir systems consist of a drug core enclosed within a membrane that controls drug release. In non-swelling reservoir systems, polymers like ethyl cellulose or polymethacrylates are used. These do not hydrate in aqueous media and control release through membrane thickness, porosity, or insolubility. This type includes...
68
01:24Site-Targeted Drug Delivery Systems: Polymeric Carriers
79
Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...
79
01:26Oral Drug Delivery Systems: Continuous-Release Systems
135
Continuous-release drug delivery systems offer a strategic approach to maintaining therapeutic drug levels over extended periods following oral administration. By modulating the release rate of active pharmaceutical ingredients, these systems minimize fluctuations in plasma concentrations, which enhances clinical efficacy and reduces the need for frequent dosing. Such characteristics make them particularly advantageous in managing chronic diseases where patient adherence and stable drug...
135
01:21Intrauterine Drug Delivery Systems
82
Controlled-release systems for intravaginal and intrauterine drug delivery have been developed primarily for the administration of contraceptive steroid hormones. These delivery routes circumvent first-pass hepatic metabolism, thereby enhancing bioavailability and allowing for reduced systemic dosages compared to oral administration. Such approaches contribute to improved therapeutic efficacy and patient compliance, particularly in long-term contraceptive regimens.Intravaginal Drug Delivery...
82
01:11Oral Drug Delivery Systems: Delayed-Release Systems
91
Delayed-release drug delivery systems are specialized pharmaceutical formulations designed to postpone the release of active compounds until the drug reaches a specific region of the gastrointestinal (GI) tract, typically the intestine. These systems are essential for drugs that may cause gastric irritation, are unstable in acidic environments, or need to exert therapeutic effects locally in the intestinal or colonic regions.The core feature of delayed-release systems is the use of enteric...
91
01:05Bioavailability Enhancement: Drug Stability Enhancement and GI Retention
292
Improving a drug's stability in the gastrointestinal (GI) tract is paramount for enhancing its bioavailability and therapeutic effectiveness. Various strategies are employed to protect the drug from the harsh gastric milieu and to ensure its release and absorption at the desired site within the GI tract.Polymer coatings are one such method used to shield drugs from the stomach's acidic environment. By preventing premature drug release, these coatings improve the bioavailability of unstable...
292