Polymer-Drug Nanoconjugate – An Innovative Nanomedicine:
Challenges and Recent Advancements in Rational Formulation Design for Effective
Delivery of Poorly Soluble Drugs
Author(s):
Amos O. Abioye, George Tangyie Chi, Adeola T.
Kola-Mustapha, Ketan Ruparelia, Ken Beresford and Randolph Arroo Pages
38 - 79 ( 42 )
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.
Affiliation:
Leicester School of Pharmacy, De Montfort
University, The Gateway, Leicester, LE1 9BH, UK.
Graphical Abstract:
0 comments:
Post a Comment