Editorial Feature

Polymeric Nanoparticles Development

Polymeric nanoparticles (PNPs) are key components in a range of products including paints, adhesives, and coatings. Current interest is in the field of biomedical products, to make use of them as drug delivery agents and diagnostic agents.

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PNPs are solid particles in colloidal form, sized 10-1000 nm. They are composed of biocompatible and biodegradable polymers or copolymers. They can be used to deliver drugs to various spots within the body, by trapping the drug within or on the surface of the polymer carrier, either by physical processes like adsorption or by chemical linkage.

The appeal of PNPs lies in their small size, the fact that they break down into natural components, are soluble in water, are non-toxic, and are stable at room temperature over the long term. Therefore, they can be loaded with various chemicals and proteins, or DNA, for use within the body.

Polymeric nanoparticle synthesis

Polymeric nanoparticles are classified into three categories:

  • From preformed polymers in dispersion, using methods such as solvent evaporation, nanoprecipitation, emulsification, dialysis, and supercritical fluid
  • From monomers by emulsification, mini emulsion, microemulsion, controlled radical polymerization, and interfacial polymerization
  • From hydrophilic polymers by ionic gelation or coacervation

In this way, PNPs may be either nanospheres or nanocapsules. The former consists of a matrix within which the drug is dispersed. The second is a drug surrounded by a polymeric membrane.

The surface of PNPs synthesized from hydrophilic polymers can be tuned using methods like PEGylation. Such changes can reduce the rate of protein adsorption, increasing the time the PNPs spend in circulation, thus enabling more of them to accumulate in the target tissue.

The polymers used to synthesize PNPs are of three types:

  • Natural hydrophilic polymers, either natural proteins like gelatin or albumin or natural polysaccharides like alginate and chitosan
  • Synthetic hydrophobic polymers, either preformed polymers like polystyrene and poly(ε-caprolactone) or polymerized during the process, such as poly(methyl methacrylate).
  • Amphiphilic block copolymers which contain polymers with both a hydrophobic and a hydrophilic group in the polymer molecule, including deblock, triblock and tetra block copolymers.

Stimuli-responsive PNPs

Conventional stimuli-responsive PNPs respond to changes in pH or temperature by a reversible phase transition. For instance, the well-known polymer poly(N-isopropyl)acrylamide dissolves easily in water at room temperature, but when heated, the precipitate is formed. This, in turn, dissolves upon cooling. The phase change is due to a conformational change from an extended chain conformation to a collapsed chain as it cools. The polymer effectively changes from a hydrophilic one to a hydrophobic one with a change in temperature.

The use of diblock copolymers in which one block is temperature-sensitive enables multiple polymer chains to aggregate into micelles non-covalently. These micelles are PNPs. These are very useful in making nanoparticles that act as drug delivery agents, for instance, releasing their cargo of small hydrophobic molecule drugs when they reach a part of the body which is at a different temperature. However, they have a restricted range of structures which in turn limits the spectrum of properties and responsiveness.

Newer PNPs

New PNPs are being developed which can respond to stimuli by changing their structure, allowing the nanoparticle to be used more effectively. For instance, they could hold the drugs in an encapsulated form within the upper gut, which is acidic, changing their physical structure to enable drug release as they move down into a more basic environment.

This stimulus-responsiveness is because they contain dynamic covalent bonds that form and dissolve as the environmental parameters change. Such alterations may include pH changes, oxidation or reduction.

Also, such covalent bonds can exchange one reaction partner for another, producing one amine in place of another, for instance. Such interactions allow these PNPs to incorporate or release new components. This could produce a new class of stimuli-responsive polymers apart from the conventional ones.

Apart from micelle formation, such diblock copolymers can be used to create core cross-linked star polymers, nanogels and single-chain polymer nanoparticles that crosslink intramolecularly to form a collapsed NP.

Liposomes are other natural PNPs that can carry drugs within the body, for cancer therapy. While limited in their ability to control the time of drug release, they are being used in the treatment of some cancers and are undergoing clinical trials for others.

PNPs are also being used in biomedical imaging, for instance, methoxy-PEG-protected poly-L-lysine (PLL) co-polymer (PGC) conjugated with dye molecules can serve as probes for in vivo imaging. Work is going on to resolve current issues with steric hindrance between the various components of the probe and the target enzyme.

Other probes PNPs to respond to apoptosis are being investigated which respond to near-infrared light by activation and fluorescence. Other sophisticated PNPs are being developed to target disease sites, find tumor locations, and release multiple tumor-killing drugs all in one.

One PNP that is currently being clinically tested is BIND-014, which has prostate-specific membrane antigen (PSMA) on the surface of a PEG-PLGA nanoparticle so that it can achieve the targeted delivery of the cancer drug docetaxel to nonsmall-cell lung cancer cells and prostate cancer cells. Another is CRLX101 (IT-101), a PNP that consists of a copolymer of cyclodextrin–polyethylene glycol (CD–PEG) covalently conjugated to the anticancer drug camptothecin (CPT).

Sources

  • Making polymeric nanoparticles stimuli-responsive with dynamic covalent bonds. Alexander W. Jackson and David A. Fulton. Polymer Chemistry, 2013, 4, 31-45. DOI: 10.1039/C2PY20727C. https://pubs.rsc.org/en/content/articlehtml/2012/py/c2py20727c
  • New generation of multifunctional nanoparticles for cancer imaging and therapy. Kyeongsoon Park, Seulki Lee, Eunah Kang, Kwangmeyung Kim, Kuiwon Choi, and Ick Chan Kwon. Advanced Functional Materials. 2009,19,1553–1566. DOI: 10.1002/adfm.200801655
  • Nanotherapeutic platforms for cancer treatment: from preclinical development to clinical application. S. P. Egusquiaguirre, J. L. Pedraz, M. Hernández, and M. Igartu. Nanoarchitectonics for Smart Delivery and Drug Targeting, 2016. https://doi.org/10.1016/B978-0-323-47347-7.00029-X.

 

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Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.

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