Development of self-immolative dendrimers for drug delivery and sensing

• Published in: Journal of controlled release Vol. 159; no. 2; pp. 154 - 163
• Main Authors: Wang, Rongsheng E., Costanza, Frankie, Niu, Youhong, Wu, Haifan, Hu, Yaogang, Hang, Whitney, Sun, Yiqun, Cai, Jianfeng
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 30.04.2012; Elsevier
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Biodegradability; Biological and medical sciences; Biosensors; Cascade-release; Cell Line, Tumor; chemical structure; Controlled release; Decomposition; Dendrimer; Dendrimers - chemistry; Dendritic amplification; Developmental stages; Drug Carriers - chemistry; Drug delivery; Drug development; drugs; Excretion; General pharmacology; Humans; image analysis; imaging; Macromolecules; Medical sciences; Models, Molecular; Molecular Structure; Permeability; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Self-immolative; Solubility; Structure-Activity Relationship; Therapeutic applications; Toxicity; Trigger; Dendrimer; Drug delivery; Trigger; Dendritic amplification; Cascade-release; Self-immolative; Pharmaceutical technology; Branched polymer; Drug carrier; Release; Dendritic structure
• ISSN: 0168-3659; 1873-4995; 1873-4995
• DOI: 10.1016/j.jconrel.2011.11.032

Traditional dendrimers possess unique cascade-branched structural properties that allow for multivalent modifications with drug cargos, targeting/delivery agents and imaging tools. In addition to multivalency, the dendrimer's macromolecular size also brings about the enhanced permeability and retention (EPR) effect, which makes it an attracting agent for drug delivery and biosensing. Similar to other macromolecules, therapeutic application of dendrimers in the human body faces practical challenges such as target specificity and toxicity. The latter represents a substantial issue due to the dendrimer's unnatural chemical structure and relatively large size, which prohibit its in vivo degradation and excretion from the body. To date, a class of self-immolative dendrimers has been developed to overcome these obstacles, which takes advantage of its unique structural backbone to allow for cascade decompositions upon a simple triggering event. The specific drug release can be achieved through a careful design of the trigger, and as a result of the fragmentation, the generated small molecules are either biodegradable or easily excreted from the body. Though still at a preliminary stage, the development of this novel approach represents an important direction in nanoparticle-mediated drug delivery and sensor design, thereby opening up an insightful frontier of dendrimer based applications. [Display omitted]