Targeted polymeric therapeutic nanoparticles: design, development and clinical translation

By N. Kamaly, Zeyu Xiao, P. Valencia, A. Radovic-Moreno, O. Farokhzad. Chemical Society Reviews, 2012

1,596 citations recorded by the source corpus.

Polymeric materials have been used in a range of pharmaceutical and biotechnology products for more than 40 years. These materials have evolved from their earlier use as biodegradable products such as resorbable sutures, orthopaedic implants, macroscale and microscale drug delivery systems such as microparticles and wafers used as controlled drug release depots, to multifunctional nanoparticles (NPs) capable of targeting, and controlled release of therapeutic and diagnostic agents. These newer generations of targeted and controlled release polymeric NPs are now engineered to navigate the complex in vivo environment, and incorporate functionalities for achieving target specificity, control of drug concentration and exposure kinetics at the tissue, cell, and subcellular levels. Indeed this optimization of drug pharmacology as aided by careful design of multifunctional NPs can lead to improved drug safety and efficacy, and may be complimentary to drug enhancements that are traditionally achieved by medicinal chemistry. In this regard, polymeric NPs have the potential to result in a highly differentiated new class of therapeutics, distinct from the original active drugs used in their composition, and distinct from first generation NPs that largely facilitated drug formulation. A greater flexibility in the design of drug molecules themselves may also be facilitated following their incorporation into NPs, as drug properties (solubility, metabolism, plasma binding, biodistribution, target tissue accumulation) will no longer be constrained to the same extent by drug chemical composition, but also become in-part the function of the physicochemical properties of the NP. The combination of optimally designed drugs with optimally engineered polymeric NPs opens up the possibility of improved clinical outcomes that may not be achievable with the administration of drugs in their conventional form. In this critical review, we aim to provide insights into the design and development of targeted polymeric NPs and to highlight the challenges associated with the engineering of this novel class of therapeutics, including considerations of NP design optimization, development and biophysicochemical properties. Additionally, we highlight some recent examples from the literature, which demonstrate current trends and novel concepts in both the design and utility of targeted polymeric NPs (444 references).

Subfields: Biomaterials, Biomedical Engineering, Pharmaceutical Science

View Paper: https://www.semanticscholar.org/paper/ae6e0a4e13c06d18d5f52d9e6b8bd0ea9872d12e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Biomaterials

1. S. Mitragotri
2. A. Anselmo
3. N. Bertrand
4. N. Kamaly
5. Xiaoyang Xu
6. Jun Wu
7. K. El-Say
8. Hossam S. El-Sawy

In Biomedical Engineering

1. S. Mitragotri
2. A. Anselmo
3. N. Bertrand
4. Xiaoyang Xu
5. N. Kamaly
6. Jun Wu
7. K. El-Say
8. Hossam S. El-Sawy

In Pharmaceutical Science

1. K. El-Say
2. Hossam S. El-Sawy
3. T. Vandamme
4. N. Bertrand
5. N. Anton
6. S. Mitragotri

Citations in the corpus

• Challenges and key considerations of the enhanced permeability and retention (EPR) effect for nanomedicine drug delivery in oncology (2013, neutral): “Recently, several actively targeted nanoparticle products have also entered clinical development, including liposomes and polymeric particles containing payloads ranging fromconventional cytotoxic drugs to genes expressing tumor suppressors (10).”
• The Advancing of Zinc Oxide Nanoparticles for Biomedical Applications (2018, background): “Targeted nanoparticles (NPs) also provide more therapeutic benefits besides specificity and specific localization like high payload, multidrug conjugation, easy tuning of release kinetics, selective localization, and bypass of multidrug resistance mechanism [70].”
• Cancer Nanomedicine: From Targeted Delivery to Combination Therapy (2015, background): “The combination of chemotherapy medications allows oncologists to use drugs at lower doses, reducing cytotoxic effects but increasing efficacy, and therefore present a promising approach for cancer research [10].”
• Nanoparticles in the clinic (2016, background): “Interestingly, while nanoparticles and targeting antibodies are both approved for clinical use, systems combining these two technologies are lacking in both approved products and in clinical trials (Table 3).(89) Considering the substantial preclinical research efforts into, and the proven benefits ”
• An overview of active and passive targeting strategies to improve the nanocarriers efficiency to tumour sites (2019, background): “The first evidence of this phenomenon was proposed in 1980 with antibodies grafted in the surface of liposomes,([27]) followed by other various kinds of ligands like for instance peptides, nucleic acids, aptamers.([28,29]) Among the classical targets, we can cite the transferrin receptors (TfR) or n”
• Polymeric nanoparticles: Promising platform for drug delivery. (2017, background): “…et al., 2000), polycaprolactone (PCL) (Wilczewska et al., 2012), poly (malic acid) (PMLA) (Kamaly et al., 2012), polyglutamic acid (PGA) (Kamaly et al., 2012), poly (methyl methacrylate) (PMMA) (Pinto Reis et al., 2006; Thickett and Gilbert, 2007), poly (N-vinyl pyrrolidone) (PVP)…”