Polymer conjugates as therapeutics: future trends, challenges and opportunities

Vicent, Marı́a J.; Dieudonné, Lucile; Carbajo, Rodrigo J.; Pineda‐Lucena, Antonio

doi:10.1517/17425247.5.5.593

Cited by 78 publications

(38 citation statements)

References 177 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nanoscience and nanotechnology are the bases of innovative delivery techniques and offer great potential benefits to patients and new markets to pharmaceutical industry. 164,165 Polymer therapeutics are nanosized hybrid constructs that covalently combine a drug, protein, or anti-body with a polymer; they can rightly be viewed as the first polymeric nanomedicines (see [166][167][168][169][170] for more information on this field). The successful clinical application of polymer-protein conjugates (PEGylated enzymes and cytokines) 171,172 and the promising results arising from clinical trials with polymer-bound chemotherapeutics 167 have established the potential of polymer therapeutics as anti-cancer therapy.…”

Section: Synthetic Inhibitors Of the Apaf-1-mediated Apoptosome Assemmentioning

confidence: 99%

“…Delivery of new anti-cancer agents focusing on novel molecular targets and their combination, development of both new and exciting polymeric materials with defined architectures and treatment of diseases other than cancer (e.g., rheumatoid arthritis, diabetes, or ischemia), are the most exciting and promising areas. 170 The latter is one of the most interesting advances in the field of polymerdrug conjugates and, in particular, the design of macromolecular systems to promote tissue regeneration. 173,174 Within this context and, in particular, tissue regeneration and ischaemic diseases, the research carried out considering the above-mentioned Apaf-1 inhibitors as bioactive agents could be enclosed.…”

Section: Synthetic Inhibitors Of the Apaf-1-mediated Apoptosome Assemmentioning

confidence: 99%

See 1 more Smart Citation

Molecules that modulate Apaf‐1 activity

Pérez‐Payá

Orzáez

Mondragón

et al. 2011

Medicinal Research Reviews

View full text Add to dashboard Cite

Programmed cell death, apoptosis, is a highly regulated cellular pathway, responsible for the elimination of cells in the organism that are no longer needed or extensively damaged. Defects in the regulation of apoptosis could be at the molecular basis of different diseases, either when it is insufficient or excessive. The formation of the macromolecular complex, apoptosome, is a key event in this pathway, which has also been defined as the intrinsic apoptosis pathway. The apoptosome is a holoenzyme multiprotein complex formed by cytochrome c-activated apoptotic protease-activating factor (Apaf-1), dATP, and procaspase-9. Recent studies have produced a wealth of information about the regulation and functions of Apaf-1, but additional studies aimed at elucidating its role as a signaling device at the crosstalk between different signaling pathways are needed to take advantage for the development of modulators of apoptosis pathways and possible therapeutic applications.

show abstract

Section: Synthetic Inhibitors Of the Apaf-1-mediated Apoptosome Assemmentioning

confidence: 99%

Section: Synthetic Inhibitors Of the Apaf-1-mediated Apoptosome Assemmentioning

confidence: 99%

Molecules that modulate Apaf‐1 activity

Pérez‐Payá

Orzáez

Mondragón

et al. 2011

Medicinal Research Reviews

View full text Add to dashboard Cite

show abstract

“…Drugs are often conjugated to the polymers via biodegradable linkers which can control the site and rate of drug liberation, although the linker has to be carefully selected to display optimal in vivo drug release rates for the intended therapeutic application [7]. It is important to note however, that the physicochemical properties of the polymer can have an impact on the in vivo liberation of drugs linked via 'biodegradable' linkers, particularly when access by an enzyme is required [1,8,9].…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Polymer-drug conjugates as inhalable drug delivery systems: A review

Marasini

Haque

Kaminskas

2017

Current Opinion in Colloid & Interface Science

View full text Add to dashboard Cite

Abstract:Accelerating interest by the pharmaceutical industry in the identification and development of less invasive routes of nanomedicine administration, coupled with defined efforts to improve the treatment of respiratory diseases through inhaled drug administration has fuelled growing interests in inhalable polymer-drug conjugates. Polymer-drug conjugates can alter the pharmacokinetics profile of the loaded drug after inhaled administration and enable the controlled and sustained exposure of the lungs to drugs when compared to the inhaled or oral administration of the drug alone. However, the major concern with the use of inhalable polymer-drug conjugates is their biocompatibility and long-term safety with the lungs, which is closely linked to their retention time in the lungs. A detailed understanding about the pharmacokinetics, lung disposition, clearance and safety of inhaled polymer-drug conjugates with significant translational potential is therefore required. This review therefore provides a comprehensive summary of the latest developments on several types of polymer-drug conjugates that are currently being explored as inhalable drug delivery systems. Finally, the current status and future perspective of the polymer-drug conjugates is also discussed with a focus on current knowledge gaps. Graphical abstract:

show abstract

“…Examples of PDCs include polymer-drug nanoconjugates; biologically active polymers; polymer-protein conjugates; polymer-antibody conjugates; drug loaded polymeric micelles and polymer-DNA complexes (polyplexes) for gene delivery etc. (11,(24)(25)(26). Because of their distinctive pharmacokinetic profiles, they are considered as new chemical entities relative to their parent drugs, not conventional pharmaceutical dosage formulation or drug delivery systems that simply physically entrap the drug (5,7,11,26).…”

Section: Polymer-drug Conjugatesmentioning

confidence: 99%

Polymer-Drug Nanoconjugate – An Innovative Nanomedicine: Challenges and Recent Advancements in Rational Formulation Design for Effective Delivery of Poorly Soluble Drugs

Abioye

Chi-Tangyie²,

Kola-Mustapha³

et al. 2016

PNT

View full text Add to dashboard Cite

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.

show abstract

Polymer conjugates as therapeutics: future trends, challenges and opportunities

Cited by 78 publications

References 177 publications

Molecules that modulate Apaf‐1 activity

Molecules that modulate Apaf‐1 activity

Polymer-drug conjugates as inhalable drug delivery systems: A review

Polymer-Drug Nanoconjugate – An Innovative Nanomedicine: Challenges and Recent Advancements in Rational Formulation Design for Effective Delivery of Poorly Soluble Drugs

Contact Info

Product

Resources

About