Polymer-drug conjugates: Progress in polymeric prodrugs

Progress in Polymer Science (Impact Factor: 26.85). 04/2006; 31(4). DOI: 10.1016/j.progpolymsci.2005.09.004

ABSTRACT Polymers are used as carriers for the delivery of drugs, proteins, targeting moieties, and imaging agents. Several polymers, poly(ethylene glycol) (PEG), N-(2-hydroxypropyl)methacrylamide (HPMA), and poly(lactide-co-glycolide) (PLGA) copolymers have been successfully utilized in clinical research. Recently, interest in polymer conjugation with biologically active components has increased remarkably as such conjugates are preferably accumulated in solid tumors and can reduce systemic toxicity. Based on the site and the mode of action, polymer conjugates possess either 'tuned' degradable or non-degradable bonds. In order to obtain such bonds, most of the strategies involve incorporation of amino acids, peptides or small chains as spacer molecules through multiple steps to include protections and deprotections. There is a need to design efficient synthetic methods to obtain polymeric conjugates with drugs and other bioactive components. Designs should aim to decrease the steric hindrance exhibited by polymers and the biocomponents. In addition, the reactivity of polymer and drug must be enhanced. This is especially true for the use of high molecular weight linear polymers and bulkier unstable drugs such as steroids and chemotherapeutic agents. Further, it is essential to elucidate the structure activity relationship (SAR) of a drug when it is conjugated with a polymer using different conjugation sites, as this can vary the efficacy and mechanism of action when compared with its free form. This review will discuss the current synthetic advances in polymer-conjugation with different bioactive components of clinical importance. In addition, the review will describe the strategies for reduction of steric hindrance and increase in reactivity of the polymers, drugs and bioactive agents and highlight the requisite structure activity relationship in polymer–drug bioconjugates. Finally, we will focus on passive and active targeting of polymeric drug delivery systems to specific site of drug action.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Biopolymer-based nanogels (bionanogels) are a promising platform as polymer-based drug delivery systems encapsulting hydrophilic anticancer therapeutics; however, enhanced/controlled drug release is highly desired. Herein, we report new dual stimuli-responsive bionanogels (ssBNGs) as potential intracellular delivery nanocarriers with multi-controlled and enhanced drug release. A facile aqueous crosslinking polymerization of oligo(ethylene oxide)-containing methacrylate (OEOMA) in the presence of carboxymethyl cellulose (CMC) and a disulfide-labeled dimethacrylate allows for the synthesis of ssBNGs crosslinked with disulfide linkages of POEOMA-grafted CMC. These ssBNGs exhibit dual response release of encapsulated anticancer drugs: reductive cleavage of disulfide crosslinks and acidic pH-response of carboxylic acid groups in CMC. Their applicability toward tumor-targeting drug delivery applications is demonstrated with confocal laser scanning microscopy for cellular uptake and cell viability, as well as a facile bioconjugation with a water-soluble UV-active dye as a model cell-targeting biomolecule.
    RSC Advances 01/2014; 4(1):229. DOI:10.1039/c3ra46072j · 3.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nanocarriers providing spatiotemporal control of drug release contribute to reducing toxicity and improving therapeutic efficacy of a drug. On the other hand, nanocarriers face unique challenges in controlling drug release kinetics, due to the large surface area per volume ratio and the short diffusion distance. To develop nanocarriers with desirable release kinetics for target applications, it is important to understand the mechanisms by which a carrier retains and releases a drug, the effects of composition and morphology of the carrier on the drug release kinetics, and current techniques for preparation and modification of nanocarriers. This review provides an overview of drug release mechanisms and various nanocarriers with a specific emphasis on approaches to control the drug release kinetics.
    Chemical Engineering Science 03/2015; 125:75-84. DOI:10.1016/j.ces.2014.08.046 · 2.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Polymers have been utilized to deliver the drug to targeted site in controlled manner, achieving the high-therapeutic efficacy. Polymeric drug conjugates having variable ligands as attachments have been proved to be biodegradable, stimuli sensitive and targeted systems. Numerous polymeric drug conjugates having linkers degraded by acidity or intracellular enzymes or sensitive to over expressed groups of diseased organ/tissue have been synthesized during last decade to develop targeted delivery systems. Most of these organs have number of receptors attached with different cells such as Kupffer cells of liver have mannose-binding receptors while hepatocytes have asialoglycoprotein receptors on their surface which mainly bind with the galactose derivatives. Such ligands can be used for achieving high targeting and intracellular delivery of the drug. This review presents detailed aspects of receptors found in different cells of specific organ and ligands with binding efficiency to these specific receptors. This review highlights the need of further studies on organ-specific polymer–drug conjugates by providing detailed account of polymeric conjugates synthesized till date having organspecific targeting.
    Journal of drug targeting 02/2015; DOI:10.3109/1061186X.2015.1016436 · 2.72 Impact Factor


Available from