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132 C. Fante et al.
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biological fluids; (c) paclitaxel contains an hydroxyl group (this can be used for
conjugation via, for instance, ester linkage); (d) paclitaxel has a short plasma half-life
(which can be prolonged by conjugation to a polymer).
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Chapter 7
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Polymeric Nanoparticles
Ijeoma F. Uchegbu
7.1 Introduction
Polymers are extensively used in pharmacy (Uchegbu and Schatzlein 2006; Sheskey
et al. 2020) and have been used for a number of years as excipients in conventional
solid dosage form and liquid medicines. Polymers also form the backbone to a
number of pharmaceutical nanoparticles, such as Abraxane, in which the polymer in
question is albumin and in which the polymer is physically bound to paclitaxel
(Green et al. 2006). COVID-19 messenger RNA (mRNA) vaccines (Hou et al. 2021)
enabled pharmaceutical nanoscience to firmly demonstrate its utility, in preventing
loss of life during the pandemic of 2020. The use of nanoparticles to deliver COVID19 nucleic acid vaccines underpinned the rapid develo pment of these vital vaccine
formulations. COVID-19 vaccine formulations are composed of mRNA particles in
which lipids were used as nucleic acid carriers. However, polymers are excellent
materials for use in the fabrication of pharmaceutical nanoparticles, as polymer
nanoparticles may be easily loaded with hydrophobic small molecules such as
cyclosporine A (Siew et al. 2012; Uchegbu et al. 2021) and propofol (Qu et al.
2006; Siew et al. 2012) and hydrophilic macromolecules such as DNA (Petkova
et al. 2022; Fatani et al. 2023) and fluorescently labelled dextran (Dufes et al. 2000).
In the case of the hydrophilic molecule dextran, this compound was encapsulated
within the aqueous interior of polymeric bilayer vesicles (Dufes et al.
example.
The biological behaviour of the resulting nanomedicines may be fine-tuned by
subtly altering the chemistry of the polymer, with more hydrophobic polymers
increasing oral bioavailability to a greater extent, for example (Le et al.
2000) for
2013), and
I. F. Uchegbu (*)
UCL School of Pharmacy, University College London, London, UK
e-mail: Ijeoma.uchegbu@ucl.ac.uk
© The Editor(s) (if applicable) and The Author(s), under exclusive license to
Springer Nature Switzerland AG 2024
I. F. Uchegbu et al. (eds.), Fundamentals of Pharmaceutical Nanoscience,
https://doi.org/10.1007/978-3-031-59478-6_7
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smaller particles, originating from more hydrophilic polymers, avoiding uptake by
the liver on intravenous administration (Lalatsa et al. 2015; Fisusi et al. 2016).
Molecular weight may also be used to optimise the delivery capability of polymer
nanoparticles. Polymer molecular weight has a direct impact on the size of the
nanoparticles (Wang et al.
polymers form particles that are more efficient in increasing drug bioavailability via
the oral route (Siew et al.
bladder gene
an 85 kDa glycol chitosan enabling gene expression in the bladder on administration
of said polyplexes directly into the bladder via the urethra; whereas 45 kDa glycol
chitosan polyplexes did not enable gene expression in the bladder (Li et al.
Increasing the molecular weight of the polymer carrier appeared to favour
mucoadhesion and hence dwell time within the bladder, leading to gene expression
in the urothelium and lamina propria.
The polymers that have been most commonly used to prepare polymeric
nanoparticles include the polyesters (e.g. poly(D,L-lactide co-glycolide) (Seju
et al.
(PLA-PEG) (Ensign et al. 2012; Hrkach et al. 2012)), chitosans (e.g. N-palmitoylN-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan—quaternary
ammonium palmitoyl glycol chitosan (GCPQ) (Uchegbu et al. 2001; Qu et al. 2006;
Lalatsa et al. 2012b), 5β-cholanicacid-glycolchitosan (Min et al. 2008), cross-linked
chitosan (Trapani et al. 2013), alginate– chitosan coacervates (Sarmento et al. 2007)),
polyamino acids (e.g. amphiphilic poly(L-lysine) and amphiphilic poly(γ-glutamic
acid) (Wang et al.
(n-butyl cyanoacrylate) (Wohlfart et al. 2011) and hyaluronic acid (Yoon et al.
2012).
Polymer nanoparticles form either by polymer self-asse mbly in aqueous media
due to their amphiphilic charact er (Qu et al. 2006), are formed by ionic gelation with
a second compound in the case of the aqueous-soluble forms of chitosan (Dyer et al.
2002; Trapani et al. 2013) or are precipitated in the presence of a suitable surface
active agent into nanoprecipitates in aqueous media due to their hydrophobicity
(Win and Feng 2006). Polymer nanoparticles may take the form of polymeric
micelles (Wang et al. 2004; Qu et al. 2006), polymeric bilayer vesicles from polymers bearing hydrophobic pendant groups (Brown et al. 1999; Wang et al. 2004),
polymeric vesicles formed from block copolymers (Discher and Ahmed 2006)or
indeed polymeric amorphous dense nanoparticles (Wang et al.
This chapter will focus mainly on polymer nanoparticles (polymeric micelles,
polymeric vesicles and dense polymeric nanoparticles) that are prepared by the
precipitation or self-assembly of polymers alone and will not deal with polymer
coatings on liposomes or polymer–drug conjugates that form nanoparticles. Liposomes and polymer–drug conjugates are covered elsewhere in this volume. Polymer
nanoparticles may be used to control the in vivo drug transport and achieve drug
targeting (Godfrey et al. 2017; Uchegbu et al.
area of pathology without significant plasma exposure. Over the years, we have been
expression of glycol chitosan polyplexes; with polyplexes formed from
2011; Yang et al. 2012), poly(D,L-lactide)-co-poly(ethylene glycol)
2000; Nakagawa 2008; Lalatsa et al. 2012c)), acrylates (e.g. poly
2001a), and, in some cases, higher molecular weight
2012)
. Molecular weight has a dramatic effect on the
2021).
2004).
2021), in which drug is confined to the
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able to correlate some of the drug delivery observations to the chemistry of the
nanoparticle-forming polymers (Le et al. 2013).
7.2 Materials Chemistry
Polymer nanoparticles for biomedical use are invariably dispe rsed within an aqueous
medium, although they may also be fashioned into solid dosage forms such as tablets
and capsules and presented as nasal powders (Siew et al. 2012; Serrano et al. 2015;
Godfrey et al. 2017). These polymer nanoparticles may be formed in three broad
ways, and each method of fabrication calls for a particular polymer chemistry.
Polymers which form nanoparticles may be hydrophobic, hydrophilic or amphiphilic
(Fig. 7.1) and polymer nanoparticles may be formed from the precipitation of a
hydrophobic po lymer (Fig.
with the polymer nanoparticle stabilised against aggregation by surfactant present in
the aqueous medium (Ensign et al.
nanoparticles from hydrophobic non-bi odegradable polym ers is to carry out an in
situ polymerisation step using a monomer to produce a hydrophobic polymer
(Fig. 7.1c), with the polymer nanoparticles once again stabilised by a hydrophilic
polymer in the aqueous media (Wohlfart et al. 2011). Hydrophilic polymers
7.1d, e) are used to prepare polymer nanoparticles by preventing their solubility
(Fig.
7.1a, b) from an organic solvent solution of the polymer,
2012). Another method of preparing polymer
Fig. 7.1 Polymers used to prepare polymeric nanoparticles: (a–c) hydrophobic polymers: (a) poly
(lactic acid-co-glycolic acid), (b) poly(lactic acid), (c) poly-n-butyl-cyanoacrylate, (d) hydrophilic
polymer: (d) chitosan (e–h) amphiphilic polymers: (e) N-palmitoyl-N-monomethyl-N,N-dimethylN,N,N-trimethyl-6-O-glycolchitosan (GCPQ), (f) poly(Nε-palmitoyl-L-lysine)-graft-poly(ethylene
oxide), (g) poly(ethylene glycol)-block-poly(lactic acid)-block-poly(ethylene glycol)
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