Neeraj Agrawal, Rohini, Anupam Joseph and Alok Mukerjee
It is well known that polymeric prodrug or polymer-drug conjugate is an effective and fast growing technique for improved use of drugs for therapeutic applications. Polymer conjugated drugs generally exhibit prolonged half-life, higher stability, water solubility, lower immunogenicity and antigenicity and specific targeting to tissues or cells. Polymers are used as carriers in polymeric prodrugs/macromolecular prodrugs for the delivery of drugs, proteins, targeting moieties, and imaging agents.
The polymeric pro-drug can be regarded as drug delivery systems that exhibit their therapeutic activities by means of releasing smaller therapeutic drug molecules from a polymer chain molecule for a prolonged period of time which results in enhanced pharmacokinetic behaviour by increasing the t1/2, bioavailability, and hence prolonged pharmacological action. The potential of the polymer-drug conjugates have already been proved by success of many products in the market for the treatment of different diseases.
A model for macromolecular pro-drugs was first proposed by Ringsdorf in the mid 1970s. The pro-drug shows particular properties determined by the macromolecule presence and manifested in the pharmacokinetic behaviour of the drug-polymer conjugate. This review deals with the Rational for design of polymer-drug conjugates, requirements for selection of drug candidate for polymeric prodrug, requirements for selecting polymers as candidate drug carriers, classification of polymers, design and synthesis of polymeric prodrugs, strategies to reduce steric hindrances exhibited by polymers and the bio-components, strategies to enhance the reactivity of polymer and the drug by incorporation of spacers and structure-activity relationship (SAR) of polymer-drug conjugates.