Background: Over the last four decades, the use of water soluble polymers in rational
formulation design has rapidly evolved into valuable drug delivery strategies to enhance
the safety and therapeutic effectiveness of poorly soluble drugs, particularly anticancer
drugs. Novel advances in polymer chemistry have provided new generations of well defined
polymeric architectures for specific applications in polymer-drug conjugate design.
However, total control of crucial parameters such as particle size, molecular weight distribution, polydispersity,
localization of charges, hydrophilic-lipophilic balance and non site-specific coupling reactions during
conjugation has been a serious challenge.
Objective: This review briefly describes the current advances in polymer-drug nanoconjugate design and various
challenges hindering their transformation into clinically useful medicines.
Method: Existing literature was reviewed.
Results: This review provides insights into the significant impact of covalent and non-covalent interactions
between drug and polymer on drug loading [or conjugation] efficiency, conjugate stability, mechanism of
drug release from the conjugate and biopharmaceutical properties of poorly soluble drugs. The utility values
and application of Quality by Design principles in rational design, optimization and control of the Critical
Quality Attributes [CQA] and Critical Process Parameters [CPP] that underpin the safety, quality and efficacy
of the nanoconjugates are also presented.
Conclusion: It was apparent that better understanding of the physicochemical properties of the nanoconjugates
as well as the drug-polymer interaction during conjugation process is essential to be able to control the
biodistribution, pharmacokinetics, therapeutic activity and toxicity of the nanoconjugates which will in turn
enhance the prospect of successful transformation of these promising nanoconjugates into clinically useful