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. 2022 Nov 29;14(12):2639. doi: 10.3390/pharmaceutics14122639

Table 2.

Physicochemical properties of the most common polymeric nanoparticles tested for drug delivery in OA treatment. Functional groups listed according to evidence from these studies.

Natural Polymers
Polymer Name Surface Chemistry
(Charge/Targeting)		 Functional Groups/Benefits Biodegradability
Chitosan Positive charge (cationic)
Active targeting possible:
  • -

    conjugation of HA onto the NP surfaces

  • -

    substitution of tripolyphosphate (TPP) by chondroitin sulfate (CS)
  • -

    PEG or PVA coating (↑ colloidal stability)

  • -

    Immobilization of anti-TNF-α and anti-IL-6 Abs at the surface (↑ anti-inflammatory effect)

  • -

    Grafting with PEI for better transfection efficiency (↑ buffering capacity, ↑ endosomal escape)

  • -

    Grafting with hydrophilic SO3− groups (↑ hydration capacity)

  • -

    Grafting with SOD (↑ antioxidant activity)

 Enzymatic degradation by lysozymes
Hyaluronic acid (HA) Negative charge (anionic)
Active targeting possible:
  • -

    natural specificity to CD44 receptor

 - Hydrolysis of β-1,4-glycosidic bonds by hyaluronidases
Synthetic Polymers
Poly(lactic-co-glycolic acid) (PLGA) Neutral charge
Active targeting possible:
  • -

    surface conjugation of collagen-binding peptide (WYRGRL)

  • -

    conjugation of HA onto the NP surfaces
  • -

    PEG coating (↑ colloidal stability)

 Hydrolysis in aqueous media, degradation rate depends on the lactide/glycolide ratio
and their molecular weights
Polylactic acid
(PLA)		 Neutral charge
  • -

    PEG coating (↑ colloidal stability)

  • -

    Surface conjugation of adenosine (ligand for A2A adenosine receptor, anti-inflammatory)

 Hydrolysis of the ester bonds, degradation rate depends on molecular weight
Polycaprolactone (PCL) Neutral charge
  • -

    PEG coating (↑ colloidal stability)

  • -

    Surface conjugation of TGFα (EGFR ligand)

 Hydrolysis of the ester bonds, slower degradation at physiological pH
Poly(hydroxyethyl) methacrylate (pHEMA) Neutral charge
  • -

    Incorporation of pyridine hydrophobic side chains to modulate particle size

 pH and thermosensitive release: ↑ solubility (drug leakage) at cloud point changes
from 28 °C to 39 °C (pH = 6.5)
Poly(N-isopropylacrylamide)
(pNIPAM)		 Neutral charge - Thermosensitive release: phase transition from a water-soluble to insoluble state at temperatures higher than the LCST (>32 °C)
Poly(amidoamine) (PAA) Positive charge (cationic) - Bioreducible NPs, cleavage of disulfide bonds by the intracellular GSH

Abbreviations: Abs: antibodies; EGFR: epidermal growth factor receptor; GSH: reduced glutathione; HA: hyaluronic acid; LCST: lower critical solution temperature; PEG: polyethylene glycol; PEI: polyethyleneimine; PVA: polyvinyl alcohol; SOD: superoxide dismutase.