Design of Tailor-Made Biopolymer-Based Capsules for Biological Application by Combining Porous Particles and Polysaccharide Assembly

Abstract

Various approaches have been described in the literature to demonstrate the possibility of designing biopolymer particles with well-defined characteristics, such as size, chemical composition or mechanical properties. From a biological point of view, the properties of particle have been related to their biodistribution and bioavailability. Among the reported core-shell nanoparticles, biopolymer-based capsules can be used as a versatile platform for drug delivery purposes. Among the known biopolymers, the present review focuses on polysaccharide-based capsules. We only report on biopolyelectrolyte capsules fabricated by combining porous particles as a template and using the layer-by-layer technique. The review focuses on the major steps of the capsule design, i.e., the fabrication and subsequent use of the sacrificial porous template, multilayer coating with polysaccharides, the removal of the porous template to obtain the capsules, capsule characterisation and the application of capsules in the biomedical field. In the last part, selected examples are presented to evidence the major benefits of using polysaccharide-based capsules for biological purposes.

Keywords: biological application; drug delivery systems; polyelectrolyte capsules; polysaccharide; porous particles.

Figure 1

Schematic illustration of (A) antibiotic-loaded calcium carbonate microparticles and (B) the fabrication of capsules coated with polysaccharides using calcium carbonate microparticles as the template. Reprinted with permission from Ref. [29]. Copyright 2020, Elsevier.

Figure 2

(Top) Representative scheme illustrating the preparation of H₂O₂-responsive multilayer films based on a phenylboronic acid polysaccharide derivative (alg-bor) and dextran. (Bottom) Illustration of the formation of a boronate ester upon the coupling of boronic acid and diol derivatives, followed by oxidation of the boronate ester to phenol by H₂O_2. Reprinted with permission from Ref. [36]. Copyright 2019, Elsevier.

Figure 3

Schematic preparation of layer-by-layer (AP/CNF)₅AP/XyG microcapsules using sacrificial CaCO₃ microparticles: (a) CaCO₃ microparticle preparation, (b) LbL assembly onto the surface of the CaCO₃ microparticles, followed by (c) the resulting hollow microcapsules. Reprinted with permission from Ref. [86]. Copyright 2017, American Chemical Society. (AP = Pectin from apple, CNF = cellulose nanofibers, XyG = xyloglucan, LbL = layer-by-layer.)

Figure 4

Structure of polymers utilised in the study by Campbell et al., separated into two categories: (A) polyanionic and (B) polycationic. For the proteins, the amino acid sequence (for PR) or the number of positively charged amino acids (Arg, Lys and His) per α1-helix (for collagen, COL) is given [87]. (HA = hyaluronic acid, CS = chondroitin sulphate, DS = dextran sulphate, HS = heparin sulphate, PLL = poly-L-lysine, PR = protamine, DA = dextran amine and COL = collagen.)

Figure 5

SEM images of a single porous CaCO₃ microsphere (a) before and (c) after uploading Nile Red and assembling polysaccharide multilayers; images (b) and (d) are images with higher magnification. (e) Typical TEM image of Nile-Red-loaded microcapsules. The inset is a relative enlarged image of a single microcapsule. Reprinted with permission from Ref. [88]. Copyright 2012, John Wiley and Sons.

Figure 6

Schematic illustration of the formation process of pectin–chitosan (Pec/Cs)₃Pec hollow nanocapsules and doxuribicin DOX@(Pec/Cs)₃Pec nanocapsules via layer-by-layer assembly. Reprinted with permission from Ref. [95]. Copyright 2017, Elsevier. (Pec = pectin, Cs = chitosan, Dox = dorubicin.)

Figure 7

Schematic representation of pH-sensitive capsule fabrication and drug delivery system. Reprinted with permission from Ref. [120]. Copyright 2022, Elsevier. (EDTA = ethylenediaminetetraacetic acid, P(EGDA-co-MAA) = poly(ethylene glycol dimethacrylate-co-methacrylic acid), Gem = gemcitabine, Cur = curcumin.)

Figure 8

The release profile of drugs from microcapsules: Gem (a) RE%, (b) RC% and Cur (c) RE%, (d) RC%. Reprinted with permission from Ref. [120]. Copyright 2022, Elsevier. Gem = gemcitabine, Cur = curcumin, RE = releasing efficiency, RC = releasing content, H = hollow microcapsule, CS = chitosan, EM = poly(ethylene glycol dimethacrylate-co-methacrylic acid.)

Figure 9

LBL assembly of autofluorescent polysaccharide-based microcapsules uploading docetaxel (Dtxl) against tumour cell proliferation. The formulated Schiff base and disulphide bonds form capsules with pH- and redox-responsive properties for pinpointed intracellular delivery based on physiological differences between the intracellular and extracellular environment. The as-obtained microcapsules could be degraded into ADA and mercaptoethylamine (MEA). Reprinted with permission from Ref. [88]. Copyright 2012, John Wiley and Sons. (PEI = poly(ethyleneimine), ADA = alginate dialdehyde, CM = cystamine dihydrochloride.)

Figure 10

CLSM images and the relative fluorescence intensity profiles of (ADA/CM)5 microcapsules in different media with FITC-dextran (2000 KDa) as a reporting molecule: (a) pH 5.0, without DTT; (b) pH 7.4, without DTT; (c) pH 7.4, with 10 mm DTT. Reprinted with permission from Ref. [88]. Copyright 2012, John Wiley and Sons. (CLSM = confocal laser scanning microscope, ADA = alginate dialdehyde, CM = cystamine dihydrochloride, DTT = dithiothreitol.)

Figure 11

Confocal microscopy image of microcapsules consisting of (alg-bor/PVPON)₅ loaded with rhodamine derivative (A) before and (B) after the addition of a solution containing glucose at pH = 8 and (C) after the addition of a solution containing glucose at pH = 2 (630× magnification). Reprinted with permission from Ref. [66]. Copyright 2019, Elsevier. (PVPON = polyvinylpyrrolidone, alg-bor = alginate derivative modified with phenylboronic acid.)

Figure 12

(A) Release of insulin from (alg-bor/PVPON)₅ capsules pH 8 in the presence of glucose solution (1 g·L⁻¹) at Δ pH 2, ■ pH 8 and x pH 8 without glucose; (B) a zoom-in of graph A. Reprinted with permission from Ref. [66]. Copyright 2019, Elsevier. (PVPON = polyvinylpyrrolidone, alg-bor = alginate derivative modified with phenylboronic acid.)