Multilayer capsules made of weak polyelectrolytes: a review on the preparation, functionalization and applications in drug delivery

Abstract

Multilayer capsules have been of great interest for scientists and medical communities in multidisciplinary fields of research, such as drug delivery, sensing, biomedicine, theranostics and gene therapy. The most essential attributes of a drug delivery system are considered to be multi-functionality and stimuli responsiveness against a range of external and internal stimuli. Apart from the highly explored strong polyelectrolytes, weak polyelectrolytes offer great versatility with a highly controllable architecture, unique stimuli responsiveness and easy tuning of the properties for intracellular delivery of cargo. This review describes the progress in the preparation, functionalization and applications of capsules made of weak polyelectrolytes or their combination with biopolymers. The selection of a sacrificial template for capsule formation, the driving forces involved, the encapsulation of a variety of cargo and release based on different internal and external stimuli have also been addressed. We describe recent perspectives and obstacles of weak polyelectrolyte/biopolymer systems in applications such as therapeutics, biosensing, bioimaging, bioreactors, vaccination, tissue engineering and gene delivery. This review gives an emerging outlook on the advantages and unique responsiveness of weak polyelectrolyte based systems that can enable their widespread use in potential applications.

Keywords: drug delivery; functionalization; multilayer capsules; synthesis; weak polyelectrolytes.

Figure 1

Schematic representation showing the capsule fabrication, drug encapsulation and release of loaded drug molecules.

Figure 2

Morphological changes in PAH/PMA capsules templated on a SiO₂ core (a–d). AFM images showing hollow capsules obtained after dissolution of SiO₂ core deposited with (a) 8 PAH/PMA (75 KDa) layers at pH 5, (b) 8 PAH/PMA (75 KDa) layers at pH 4.5, (c) 16 PAH/PMA (75 KDa) layers at pH 4.5, (d) 8 PAH/PMA (790 KDa) layers at pH 4.5 and (e) SEM image of PAH/PMA capsule deposited on CaCO₃ core. (Images a–d adapted and reprinted with permission from [24], copyright 2006 American Chemical Society. Image e reprinted from [29], copyright 2010 Elsevier B.V.).

Figure 3

Illustration of driving forces for capsule assembly. (a) Opening of electrostatically bound multilayers upon change in physiological conditions, (b) SEM investigation of hydrogen bonded, temperature sensitive (PMA/PVCL)₅ capsules, (c) TEM investigation of 440 nm SiO₂ particles coated with PAH/PAA multilayers before (left) and after (right) covalent crosslinking with EDC and (d) host–guest PAH-cyclodextrin and PAH-ferrocene microcapsule assembly. Image b was adapted and reprinted with permission from [38], copyright 2005 American Chemical Society, image c was adapted and reprinted with permission from [26], copyright 2003 John Wiley and Sons, and image d was adapted and reprinted with permission from [39], copyright 2008 American Chemical Society.

Figure 4

CLSM images of PAH/PMA microcapsules incubated with FITC-BSA at (a) pH 3 and (b) pH 7. SEM investigation of (c) a BSA-loaded capsule at pH 3 and (d) a capsule after the release of BSA at pH 7.4. The images in a–d were reprinted with permission from [70], copyright 2010 Elsevier B.V.

Figure 5

The morphological investigation of PAH/DS capsules incorporating silver NPs by (a) TEM, (b) AFM and (c) its rupture after laser irradiation. The images in a–c are reprinted with permission from [74], copyright 2011 Elsevier.

Figure 6

(a) Illustration of the fabrication of PAH/GO microcapsules, (b) CLSM investigation showing the encapsulation of Dox and FITC-BSA in PAH/GO capsules and (c) the response of the GO/PAH capsules to laser light at 1064 nm over an exposure time of 5 to 45 s. The images in a,b were republished with permission from [117], copyright 2012 Royal Society of Chemistry and the image in c was republished with permission from [118], copyright 2013 Royal Society of Chemistry.

Figure 7

Schematic illustration of (a) the formation of PVP/TA capsules loaded with Dox, (b) the ultrasound triggered release of Dox, along with images from a morphological investigation of the capsules by (c) AFM and (d) SEM. The images in a–d were adapted and reprinted with permission from [163], copyright 2017 American Chemical Society.

Figure 8

(a) Schematic representation showing the assembly of MnP-PVP/TA multilayers on silica template to obtain a hollow capsule for ROS scavenging. TEM investigation of PAH/DS microcapsules incorporating (b) gold nanorods and (c) gold bipyramids for catalysis application. The image in a was adapted and reprinted with permission from [189], copyright 2017 American Chemical Society and the images in b,c were adapted and reprinted with permission from [190], copyright 2019 American Chemical Society. Further permissions related to the material excerpted should be directed to the American Chemical Society.