Biodegradable hydrophobic polysaccharide-based coatings

Abstract

Implantable medical articles having a coating formed of hydrophobic derivatives of natural biodegradable polysaccharides are described. The coatings can include a bioactive agent, and demonstrate desirable bioactive agent release profiles and can be prepared to have high drug loading. The coated implantable medical articles can be used to treat medical conditions, such as those requiring prolonged administration of the bioactive agent at a target location in the body.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001]The present non-provisional Application claims the benefit of commonly owned provisional Application having Ser. No. 60 / 782,957, filed on Mar. 15, 2006, and entitled HYDROPHOBIC DERIVATIVES OF NATURAL BIODEGRADABLE POLYSACCHARIDES; and commonly owned provisional Application having Ser. No. 60 / 900,853, filed on Feb. 10, 2007, and entitled BIODEGRADABLE HYDROPHOBIC POLYSACCHARIDE-BASED DRUG DELIVERY IMPLANTS; which Applications are incorporated herein by reference in their entirety.TECHNICAL FIELD [0002]The present invention relates to biodegradable coatings for implantable medical articles. The method also relates to methods for treating medical conditions by releasing a bioactive agent from the coatings to a subject.BACKGROUND [0003]Coatings formed on the surface of medical devices have been shown to be beneficial as they can improve the properties of the device in one or more ways. As examples, coatings can provide the surface of implan...

AI Technical Summary

Benefits of technology

[0204]The bioactive agent can be released for a period of time and in an amount sufficient to treat a medical condition in a subject, such as one suffering from a cardiovascular disease or compilation. One distinct advantage of the present invention are that bioactive agents can be released from the coating at a steady rate, meaning that there is not substantial variation in amount of bioactive agent released per day over the bioactive agent release period of the coating. Given this, the coatings of the invention allow for drug delivery that is close to a zero-order release rate. The bioactive agent can also be released in therapeutically effective amounts for treatment of medical conditions.

[0205]In some aspects, the bioactive agent is released at an average rate in the range of 10 ng / day to 10 μg / day. In more specific aspects, the bioactive agent is released at an average rate in the range of 100 ng / day to 7.5 μg / day. In yet more specific aspects, the bioactive agent is released at an average rate in the range of 500 ng / day to 5 μg / day. In yet more specific aspects, the bioactive agent is released at an average rate in the range of 750 ng / day to 2.5 μg / day. In yet more specific aspects, the bioactive agent is released at an average rate of approximately 1 μg / day.

[0206]Another distinct advantage is that the coatings can be prepared having a particularly long bioactive agent release period, in which therapeutically effective amounts of bioactive agent are able to be released at later points during this period. With regard to bioactive agent release, the coating can have a “half-life,” which is the period of time at which half of the total amount of bioactive agent that is present in the coating is released during the bioactive agent release period.

[0207]For example, in one aspect, 50% of the amount of bioactive agent present in the coating is released from the coating after a period of 100 days. In this regard, the coating can be used for the treatment of medical conditions wherein bioactive agent is to be released for a period of time of about 3 months or greater, a period of time of about 6 months or greater, a period of time of about 9 months or greater, a period of time of about 12 months or greater, a period of time in the range of about 3 to about 6 months, a period of time in the range of about 3 to about 9 months, a period of time in the range of about 3 to about 12 months, or a period of time in the range of about 3 to about 24 months.

[0208]In some aspects, depending on the properties of the implant, a carbohydrase can promote the degradation of the coating. For example, the groups pendent from the polysaccharide backbone can be released by hydrolytic cleavage, and a portion of the coating can become accessible to a carbohydrase, which can enzymatically digest the polysaccharide and degrade the coating.

[0209]In these aspects, hydrolysis of the ester bond, which can occur non-enzymatically, and enzymatic hydrolysis of the linkages between the monomeric (or dimeric) units of the polysaccharide portion can contribute to degradation of the coating. For example, non-enzymatic hydrolysis can lead to cleavage and loss of the pendent group comprising the hydrocarbon segment from the coating. This loss may lead to a portion of the article becoming more hydrophilic, and subject to attack by a carbohydrase resulting in biodegradation of the polysaccharide, and / or further decomposition of the coating by loss of the polysaccharide from the surface.

Problems solved by technology

Injection of drugs can have limitations, for example, by requiring multiple administrations, increasing risk of complications (such as infection), and patient discomfort.

However, the molecular weight, porosity of the polymer, a greater percentage of coating exposed on the medical device, and the thickness of the polymer coating can contribute to adverse reactions to the medical device.

These types of biodegradable materials, however, have the potential to degrade into products that cause unwanted side effects in the body by virtue of their presence or concentration in vivo.

These unwanted side effects can include immune reactions, toxic buildup of the degradation products in the body, or the initiation or provocation of other adverse effects on cells or tissue in the body.

Several other challenges confront the use of medical devices or articles that release bioactive agents into a patient's body.

For example, treatment may require release of the bioactive agent(s) over an extended period of time (for example, weeks, months, or even years), and it can be difficult to sustain the desired release rate of the bioactive agent(s) over such long periods of time.

While advances in site-specific implantable drug delivery systems have been made, many systems do not release drug in a desired manner following implantation in a patient.

For example, in many systems the majority of the drug present in the article is released from the device in an initial burst, resulting in premature depletion of the drug.

If drug is prematurely released from the implant, or not released until later, the duration of treatment or the rate of release may not be as long as desired.

This can cause the implant to be therapeutically less effective.

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