Abstract
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 nanomedicines.
Keywords: Controlled biodistribution, critical quality attributes, nanoconjugate stability, polymer-drug nanoconjugates, poorly soluble drugs, rational formulation design.
Graphical Abstract
Call for Papers in Thematic Issues
Polymeric nanocarriers in drug delivery
Polymeric nanocarriers play a crucial role in drug delivery due to their versatility, and unique properties for targeting and modifying drug release. Their ability to enhance therapeutic outcomes, reduce side effects, and enable the delivery of drugs in a more targeted and controlled manner made them popular in the last ...read more
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