Implantable drug delivery devices for localized drug delivery
Inventors
Rairkar, Maithili • Desai, Pujan • Schuler, Carlos • Daud, Maxime • Rappaport, Maxime D. • Munster, Pamela • Maroney, John • McLaughlin, Margaret • Casab, Tobias H. • Hall, Keith • Thomas, Scott
Assignees
University of California San Diego UCSD • Alessa Therapeutics Inc
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Publication Number
US-11173291-B2
Publication Date
2021-11-16
Expiration Date
Abstract
Provided herein are drug implants comprising a therapeutically active agent for the treatment of disease in a subject. In some cases, the drug implant may comprise a polymer matrix and a therapeutically active agent disposed therein. Additionally provided are methods for manufacturing the drug implants and methods of treating diseases with the implants. In some cases, the drug implant may comprise bicalutamide, e.g., for use in the treatment of prostate cancer.
Core Innovation
The invention relates to implantable localized drug delivery devices, including a prostate implant for delivering bicalutamide using a drug/polymer composite. The prostate implant includes a silicone rubber matrix with a Shore A hardness of at least 30 durometer, and bicalutamide is present in solid form and dispersed within the silicone rubber matrix.
The bicalutamide is characterized by particle size, including a D90 of less than 15 microns, and is present at an amount of at least 30% w/w of the total implant. The silicone rubber matrix is non-biodegradable and is described as remaining at a high level after implantation.
The implant is configured to release bicalutamide over an extended period after implantation, including release measured at 2 years. The document links formulation and structure parameters such as particle size and silicone hardness, and describes delivery of the implant via needle/cannula catheter administration and ultrasound visibility.
Claims Coverage
The disclosed claims are centered on a single independent claim covering a silicone rubber matrix prostate implant containing solid bicalutamide with defined particle size, loading level, mechanical hardness, and a specified long-term in vivo release window at 2 years. Dependent claims further refine quantitative formulation and physical properties and narrow delivery and structure-related features.
Silicone rubber matrix prostate implant with Shore A hardness
A drug/polymer composite prostate implant comprising a silicone rubber matrix having a Shore A hardness of at least 30 durometer.
Solid bicalutamide with fine particle size dispersed in matrix
Bicalutamide in solid form having a D90 of less than 15 microns dispersed in the silicone rubber matrix.
High bicalutamide loading in implant
Bicalutamide dispersed in the silicone rubber matrix at an amount of at least 30% w/w of the total implant.
Specified long-term bicalutamide release at 2 years
The prostate implant releases between 0.6 µg/day and 10 µg/day of the bicalutamide at 2-years after implantation in a subject.
Increased bicalutamide loading threshold
The prostate implant further specifies bicalutamide dispersed in the silicone rubber matrix at an amount of at least 40% w/w of the total implant.
Median particle size constraint for solid bicalutamide
The prostate implant is made in a solid form having a median particle size of less than 10 microns.
Silicone curing temperature below bicalutamide melting point
The prostate implant includes silicone whose curing temperature is less than the melting point of bicalutamide.
Crystalline bicalutamide solid form
The prostate implant includes bicalutamide that is present in crystalline form.
Needle cannula deliverability
The prostate implant is deliverable using a cannula of a needle.
Overall, the claim coverage is directed to a prostate implant that combines a silicone rubber matrix of at least 30 durometer hardness with finely sized solid bicalutamide (D90 <15 microns) dispersed at high loading (≥30% w/w) and delivering bicalutamide within a specified 2-year release range. Dependent claims additionally constrain loading (e.g., ≥40% w/w), particle size metrics (e.g., median <10 microns), silicone curing relative to bicalutamide melting point, bicalutamide crystalline form, and administration using a needle cannula.
Stated Advantages
Enhanced local prostate drug distribution versus systemic circulation.
Reduced systemic exposure.
Documented Applications
Implantable localized drug delivery for prostate treatment using a prostate implant that releases bicalutamide over an extended period after implantation.
Use of needle/cannula catheter administration for delivering the prostate implant, including ultrasound visibility.
Preclinical canine evaluation of device safety and tissue distribution/prostate biopsy quantitation, with plasma bicalutamide levels described in the document.
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