Particulate Constructs For Release of Active Agents

Abstract

Particulate constructs stabilized by amphiphilic copolymers and comprising at least one active coupled to a hydrophobic moiety provide sustained release of the active in both in vitro and in vivo environments.

Description

RELATED APPLICATION[0001]This application claims benefit of U.S. application Ser. No. 60 / 589,164 filed 19 Jul. 2004, which is incorporated herein by reference in its entirety.TECHNICAL FIELD[0002]The description relates to compositions and methods for improved delivery and performance of active agents. More particularly, the invention concerns particulate constructs stabilized by an amphiphilic compound and comprising at least one active agent coupled through a linker to a hydrophobic moiety, which agent can be released from the construct by cleavage of the linker.BACKGROUND ART[0003]Sustained release is desirable in many applications to provide optimal use and effectiveness of active agents, including pharmaceuticals, cosmetics, food, and fragrances. Attempts have been made to solubilize, target, stabilize, and control the release of substances, including use of microparticles, nanoparticles, and polymer conjugation.[0004]Approaches based on using polymer encapsulation to formulate...

AI Technical Summary

Benefits of technology

[0024]The present invention provides particulate constructs that can be adapted to the release of active agents of various types useful in both pharmaceutical and non-pharmaceutical applications. These delivery systems provide high loading capacity for active compounds as well as provide a means for controlled release of the active, reduction in toxicity where relevant, and, if desired, selective delivery to a target site. The active agents may include various therapeutic agents such as platinum agents, taxanes and antibiotics, actives important in other applications such as pigments, dyes, fragrances and flavors, and may be applied in in vivo therapeutic and diagnostic contexts, in agricultural applications and in industrial uses.

[0031]In various embodiments, the active may be a fragrance, a pharmaceutical, a diagnostic agent, a toner, or any compound with a desirable activity. As noted in formula (I), a multiplicity of active compounds may be coupled to the same hydrophobic moiety, which may be a hydrophobic polymer with multiple linking sites, or a smaller molecule, such as a vitamin or steroid. More than one type of active agent may also be included, making the constructs particularly useful for combination therapy. In any event, by providing the delivery vehicle in this form, controlled release of the active, either over time or at a desired site, is facilitated.

Problems solved by technology

This approach is not effective in smaller particles, such as nanoparticles.

While the art provides many descriptions for preparation of nanoparticles containing active agents, none is completely satisfactory.

Conjugation of drugs to PEG has been shown to provide long circulation times in vivo, and increases the solubility of hydrophobic drug.

According to this disclosure, other phospholipids such as phosphatidyl inositol and phosphatidyl glycerol are unworkable in this system.

Despite the substantial number of preparations of microparticle, matrix chelator and nanoparticle formulations designed for drug delivery and other applications, an ideal composition has not been achieved.

Due to this complexity, achieving cures with a single agent has been met with limited success.

Administration of free drug cocktails often results in rapid clearance of one or all of the drugs before reaching the tumor site.

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