Aerogels as Carriers for Oral Administration of Drugs: An Approach towards Colonic Delivery

Abstract

Polysaccharide aerogels have emerged as a highly promising technology in the field of oral drug delivery. These nanoporous, ultralight materials, derived from natural polysaccharides such as cellulose, starch, or chitin, have significant potential in colonic drug delivery due to their unique properties. The particular degradability of polysaccharide-based materials by the colonic microbiota makes them attractive to produce systems to load, protect, and release drugs in a controlled manner, with the capability to precisely target the colon. This would allow the local treatment of gastrointestinal pathologies such as colon cancer or inflammatory bowel diseases. Despite their great potential, these applications of polysaccharide aerogels have not been widely explored. This review aims to consolidate the available knowledge on the use of polysaccharides for oral drug delivery and their performance, the production methods for polysaccharide-based aerogels, the drug loading possibilities, and the capacity of these nanostructured systems to target colonic regions.

Keywords: aerogels; colonic drug delivery; inflammatory bowel diseases; oral administration; polysaccharides; porous systems.

Figure 6

(A) Stepwise procedure for polysaccharide-based aerogel preparation. (B) Crosslinking techniques for gelation: (i) NIPS, (ii) pH-induced gelation, (iii) temperature-induced gelation, (iv) chemical gelation, and (v) ionotropic gelation. Image adapted from [17]. (C) CO₂ phase diagram used for the SCF drying process. CO₂ is continuously pumped and heated until SCF drying temperature and pressure conditions are achieved. After drying, depressurization must be carried out at a specific temperature and flow rate until the atmospheric pressure is reached. Image adapted from [107].

Figure 1

Physiological factors (transit time, luminal pH, and microbiome) in the GIT of healthy and IBD patients influence oral drug delivery. Image adapted from [3].

Figure 2

Cumulative drug release from coated formulations. The core is based on drug/alginate (1:6 weight ratio) coated with solutions of Eudragit^® S-100 with different concentrations (2.5% and 5% w/v). Notation: * Statistically significant difference at p < 0.001. ** Statistically significant difference at p < 0.0001 from 1:5 sample as determined by Student’s t-test. Image adapted from [74].

Figure 3

Mesalazine release profiles in the simulated digestive fluids for calcium pectin–silica and calcium pectinate gel beads based on the SVC (A) and AU701 (B) pectins. The formulations with high silica concentrations (22.2 mg/mL, Si22) and extended crosslinking times (60 min, 60) demonstrated the most suitable drug release profiles for colonic drug delivery applications. Image adapted from [83].

Figure 4

(A) Representation of the different layers that comprise the OPTICORE™ drug tablet system. (B) Effect of the starch-Eudragit outer layer on drug release patterns from several formulations, as follows: (F1) Single layer Eudragit^® S coating; (F2) Phloral layer (resistant starch and Eudragit S, without alkaline layer); (F3) Inner layer neutralized Eudragit^® S and outer layer Eudragit^® S; (F4) Outer layer Phloral™ (OPTICORE™) in Krebs buffer solution (pH 7.4). (C) Effect of the starch-Eudragit outer layer in drug release from formulations (mentioned in 7.B) in fecal human slurry (pH 6.8). Image adapted from [85].

Figure 5

Dissolution profiles of (A.i,B.i) diltiazem into the simulated intestinal fluid (SIF) without β-mannanase and release profiles of the drug from formulations prepared with Japanese KGM (A.i,A.ii) and American KGM (B.i,B.ii), and (A.ii,B.ii) containing various concentrations of β-mannanase for formulations J7 (A.i,A.ii) and A7 (B.i,B.ii). Image extracted from [89].

Figure 7

Strategies for preparing drug-loaded aerogels. (A) Incorporating the drug into the gel solution; (B) Adding the drug into the solvent for loading in the gels by solvent diffusion; (C) Adding the drug during the SCF drying process; (D) Loading the drug into the pre-prepared aerogels by impregnation technique. Notation: Red dots represent the drug that is loaded in the aerogel carrier.

Figure 8

Main monomer functional groups of polysaccharide aerogels. Image adapted from [110].

Figure 9

(A) Representation of external, internal, or inverse gelation. This figure illustrates the gelation process of alginate with Ca²⁺ as an example, but the underlying concept is applicable to various polymers and crosslinking agents. The arrows indicate the direction of the crosslinking front. (B) Preparation of aerogel microparticles by internal gelation and external gelation. Image extracted from [100]. (C) Dripping gelation modalities: (i) conventional, (ii) vibrating, (iii) electrostatic, and (iv) jet-cutting dripping methods. Image extracted from [17].

Figure 10

Release profiles of celecoxib (raw material) and celecoxib-loaded starch aerogels in different dissolution media (A) SGF medium and (B) SIF medium and paddle speeds (50 and 100 rpm). Significant enhancements can be observed in the cumulative release percentage of celecoxib from the starch aerogel systems compared to the raw material under all tested conditions. Image extracted from [111].

Figure 11

Comparison of nifedipine release profiles from its raw crystalline state and pectin aerogels loaded via two distinct methods, solvent exchange in ethanol (EtOH) and in supercritical fluids (SCF), in two dissolution media: (A) SGF (pH 1.2) and (B) PBS (pH 7.4). Image extracted from [112].

Figure 12

Drug release profiles in PBS medium from different polysaccharide-based aerogels: (A) pectin, (B) alginate, and (C) alginate–pectin (1:1), ionically crosslinked with divalent calcium ions (PC⁺), strontium ions (PS), and zinc ions (PZ). The figure illustrates the differences between aerogels produced with different compositions as well as the substantial effect of the type of crosslinking agent on drug release. Image extracted from [114].

Figure 13

Release profiles of ibuprofen from a crystalline form and coated and uncoated aerogels in PBS medium (pH 7.4). Image extracted from [131].