Polymeric Hydrogels as Technology Platform for Drug Delivery Applications

Abstract

Hydrogels have become key players in the field of drug delivery owing to their great versatility in terms of composition and adjustability to various administration routes, from parenteral (e.g., intravenous) to non-parenteral (e.g., oral, topical) ones. In addition, based on the envisioned application, the design of bioadhesive or mucoadhesive hydrogels with prolonged residence time in the administration site may be beneficial. For example, hydrogels are used as wound dressings and patches for local and systemic therapy. In a similar way, they can be applied in the vaginal tract for local treatment or in the nasal cavity for a similar goal or, conversely, to target the central nervous system by the nose-to-brain pathway. Overall, hydrogels have demonstrated outstanding capabilities to ensure patient compliance, while achieving long-term therapeutic effects. The present work overviews the most relevant and recent applications of hydrogels in drug delivery with special emphasis on mucosal routes.

Keywords: bioadhesion and mucoadhesion; drug delivery; hydrogels; ocular delivery; oral delivery; rectal delivery; topical delivery; transdermal delivery; vaginal delivery.

Figure 1

Hydrogels and tissue engineering. Schematic diagram of the use of hydrogels in (A) microencapsulation and (B) tissue-engineering scaffold. (Reprinted with permission from reference [16]. Copyright 2014 Elsevier).

Figure 2

Preparation of alginate hydrogels coated with chitosan for wound dressing. (Reprinted from reference [20]).

Figure 3

(a,b) Microscopic images of mesenchymal stromal cells (MSC) cultured for seven days in control culture medium after crystal violet staining; (c,d) microscopic images of MSC cultured for seven days in 0.1% chitosan hydrochloride culture medium after crystal violet staining. (Reprinted from reference [20]).

Figure 4

Schematic representations of Pluronic^® F127 micelles: (a) single micelle with spherical core-shell geometry; (b) single 2D hexagonally packed layer of micelles; (c) two 2D hexagonally packed layers of micelles (AB); and (d) three layers with ABC (or Faced Centered Cubic, FCC) stacking sequence structure. (b–d) correspond to the radial geometry. (Reprinted with permission from reference [32]. Copyright 2007 American Chemical Society).

Figure 5

Tetracycline release profiles from poloxamer (- - -) and monoglyceride (―) based gels. Kinetics were determined by equilibrium dialysis. The reported values represent the average of five independent experiments, bars = S.D. (Reprinted with permission from reference [34]. Copyright 1996 Elsevier).

Figure 6

Correlation between in vitro pilocarpine release and pupillary constriction obtained in vivo. A linear correlation is evident with an R² of 0.97. As the amount of pilocarpine available for absorption decreases, a corresponding increase in pupil diameter is observed. Data are reported as mean ± SEM. Solid line indicates the best-fit line and dashed line indicates the 95% confidence interval. (Reprinted with permission from reference [1]. Copyright 2009 Elsevier).

Figure 7

Hematoxylin and Eosin staining to visualize the histology of CEES and NM-exposed corneas treated for 24 h with doxycycline in solution or in a hydrogel. The damaged area is where the epithelium meets the stroma. The wound-healing efficacy of doxycycline solution was close to the doxycycline hydrogel for CEES exposed corneas, as the extent of damage was comparatively mild. However, a superior wound healing efficacy was observed with hydrogels over solutions when harshly damaged NM-exposed corneas were treated with doxycycline. CEES: half mustard; NM: mustard; DOXY: doxycycline. (Reprinted with permission from reference [45]. Copyright 2010 Elsevier).

Figure 8

Concept behind hydrogels of poly[(propylenesulfide) (PPS)-(N,N-dimethylacrylamide) (DMA)-(N-isopropylacrylamide) (PNIPAAM) that undergo reversible gelation at 37 °C and degrade upon exposure to ROS. (Reprinted with permission from reference [26]. Copyright 2014 American Chemical Society).

Figure 9

Schematic of aFGF-heparin (HP) thermo-sensitive hydrogels enhance the recovery of spinal cord injury (SCI). The protection of aFGF-HP containing blood-spinal cord barrier (BSCB) protection, neuroprotection, remyelination, attenuation of astrogliosis, axon elongation in three different stages after SCI, which are the main obstacles to recovery of SCI. (Reprinted with permission from reference [50]. Copyright 2017 American Chemical Society).

Figure 10

Representative TEM micrographs for the aqueous dried AgNPs (100 μg AgNPs/mL): (A) uncoated AgNPs; (B) SDS-coated AgNPs; (C) PEG-coated AgNPs (×100,000); (D) β-CD-coated AgNPs (×140,000) with sizes = 15.7 ± 4.8, 13 ± 4, 19.2 ± 3.6, and 14 ± 4.4 nm, respectively (n = 50, bar represents 100 nm). Insets indicate histograms of AgNPs size distribution. Abbreviations: TEM, transmission electron microscopy; AgNPs, silver nanoparticles; SDS, sodium dodecyl sulfate; PEG, polyethylene glycol; β-CD, β-cyclodextrin. (Reprinted from reference [52]).

Figure 11

Successive images of representative mice skin abrasion wounds infected with MRSA at different time intervals. Two groups were treated with 0.1% silver nanoparticles (AgNPs) hydrogel and 1% silver sulfadiazine cream. The two other groups were the blank hydrogel-treated group and control untreated mice. Abbreviations: MRSA, methicillin-resistant Staphylococcus aureus; AgNPs, silver nanoparticles. (Reprinted from reference [52]).

Figure 12

(A) Schematic illustration of the preparation of pectin/starch hydrogels encapsulated Lactobacillus plantarum (L. plantarum) cells. (B) Release profile of encapsulated cells in buffered solution with pH 1.2 and pH 7.4; Values shown are means ± standard deviations (n = 3). (Reprinted with permission from reference [57]. Copyright 2017 Elsevier).

Figure 12

(A) Schematic illustration of the preparation of pectin/starch hydrogels encapsulated Lactobacillus plantarum (L. plantarum) cells. (B) Release profile of encapsulated cells in buffered solution with pH 1.2 and pH 7.4; Values shown are means ± standard deviations (n = 3). (Reprinted with permission from reference [57]. Copyright 2017 Elsevier).

Figure 13

Percentages of paracetamol release from the hydroxyethylacryl chitosan (HC)/sodium alginate (SA) hydrogels after immersing in simulated gastric fluid (SGF) for 2 h followed by simulated intestinal fluid (SIF) for 6 h at 37 °C: (a) varying ratios of HC to SA and (b) HC50SA50 with varying cross-linker types). (Reprinted with permission from reference [61]. Copyright 2017 Elsevier).