Polymeric Prodrugs: Recent Achievements and General Strategies

Rohini Neeraj Agrawal,Anupam Joseph Alok Mukerji

doi:10.4172/jaa.s15-007

Abstract

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.

Highlights

Improving the therapeutic index of drugs is a major impetus for innovation in many therapeutic areas
The results showed that the drug release from the polymeric backbone takes place in a sustained manner over a period of 24 h, and the amount of drug released was comparatively higher at pH 7.4
The results showed that the drug release from the polymeric backbone takes place in a sustained manner over a period of 24 h and the amount of drug released was comparatively higher at pH 7.4 indicating that the drug release takes place predominantly at the alkaline environment of the lower GIT rather than at the acidic environment of the upper GIT

Summary

Introduction

Improving the therapeutic index of drugs is a major impetus for innovation in many therapeutic areas. For example a) Conjugate of plant toxins and antibodies, referred as immunotoxin is a very potent antitumor therapy b) Tumor selective monoclonal antibody is covalently attached to an enzyme which converts non toxic prodrug into potent cytotoxic drug after specific targeting at the tumor site [30]. It has been reported that treatment with free anti-tumor drugs promotes induction of Fas ligands on cancer cells whereas their macromolecular derivatives did not increase Fas L [37] This is an important outcome that might indicate that polymeric prodrugs are able to protect the patient’s immune system. Advantages: Non immunogenic, non toxic, resides in blood circulation well It is frequently used as macromolecular carriers for low molecular weight drugs (especially anti-cancer chemotherapeutic agents) to enhance therapeutic efficacy and limit side effects [40].

Coupling methods

D D a DD D b

Findings

Conclusion