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.

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    • "CLZ exerts its action by binding to the benzodiazepine site of the GABA receptors, which causes an enhancement of the electric effect of GABA binding on neurons resulting in an increased influx of chloride ions into the neurons. This results in an inhibition of synaptic transmission across the central nervous system [1] [2] [3] [4] [5] [6] [7] [8]. "
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    ABSTRACT: Many FDA approved drugs currently available in the market have limitations in crossing the blood brain barrier (BBB) owing to its complicated vasculature posed by the presence of specialized cells One of the most challenging problems, if not the most challenging, in drug development is not to develop drugs to treat diseases of the central nervous system (CNS), but to manage to distribute them to the CNS across the blood–brain barrier. The development of BBB targeting technologies is a very active field of research and development. One goal is to develop chemically modified derivatives of CNS drug (clonazepam) chemically modified nanoparticulate of drugs, capable of crossing biological barriers, in particular the BBB. Nanocarrier drug delivery involves targeting CNS drugs enclosed in a particular PVP polymer. Drug nanoparticles have been shown to improve bioavailability and enhance drug exposure for oral and parenteral dosage forms. Nanoparticles of clonazepam were prepared by many methods.
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    • "However, PNVaided chemotherapy appears to suffer from several physical barriers during the transport process [5] [6]. Unlike small drug molecules, PNVs are unable to diffuse through the cell membrane but undergo intracellular internalization via an energy-dependent endocytotic pathway [7] [8]. The entrapment of drug-loaded PNVs inside endosome/lysosome organelles is a significant limiting factor affecting the drug efficacy [9] [10] [11]. "
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    Acta Biomaterialia 05/2014; 10(8). DOI:10.1016/j.actbio.2014.05.018 · 5.68 Impact Factor
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    • "This passive tumor targeting is achieved primarily through the enhanced permeability and retention effect. In past decades, conjugation of hydrophilic polymers with hydrophobic anticancer drugs (such as paclitaxel, doxorubicin, camptothecin, and curcumin) to produce polymer-drug conjugate systems has been proven to be a viable formulation strategy.17–25 A large number of hydrophilic polymers could be chosen as water-soluble macromolecule carriers; among them, poly(ethylene glycol) (PEG) is considered to be one of the best candidates. "
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