Alginate Particles as Platform for Drug Delivery by the Oral Route: State-of-the-Art

Abstract

Pharmaceutical research and development aims to design products with ensured safety, quality, and efficacy to treat disease. To make the process more rational, coherent, efficient, and cost-effective, the field of Pharmaceutical Materials Science has emerged as the systematic study of the physicochemical properties and behavior of materials of pharmaceutical interest in relation to product performance. The oral route is the most patient preferred for drug administration. The presence of a mucus layer that covers the entire gastrointestinal tract has been exploited to expand the use of the oral route by developing a mucoadhesive drug delivery system that showed a prolonged residence time. Alginic acid and sodium and potassium alginates have emerged as one of the most extensively explored mucoadhesive biomaterials owing to very good cytocompatibility and biocompatibility, biodegradation, sol-gel transition properties, and chemical versatility that make possible further modifications to tailor their properties. The present review overviews the most relevant applications of alginate microparticles and nanoparticles for drug administration by the oral route and discusses the perspectives of this biomaterial in the future.

Figure 1

Progression of the number of scientific articles in the search engine Scopus for alginate particles over the last decade.

Figure 2

Structure of ALG. Reproduced from [21] with permission of Elsevier.

Figure 3

Schematic drawing and calcium coordination of the “egg-box” model, as described for the pair of guluronate chains in calcium ALG junction ones. Dark circles represent the oxygen atoms involved in the coordination of the calcium ion. Reproduced from [31] with the permission of the American Chemical Society.

Figure 4

Concept for the production of uniform size-controlled microparticles with inkjet printer. (a) Microparticles are easily fabricated by evaporating moisture in air, and (b) size of particles could be controlled with changing the concentration of the biomaterial. Reproduced from [86] with permission of Elsevier.

Figure 5

SEM micrographs of ALG microparticles fabricated by inkjet/drying using a 0.8% ALG solution. Reproduced from [86] with permission of Elsevier.

Figure 6

Animal survival profile over 17 weeks. Control group animals gavaged with drug-free ALG-chitosan microcapsules suspended in PBS and treatment group animals gavaged with microencapsulated oxaliplatin nanoparticles suspended in PBS. Reproduced from [91] with permission of Elsevier.

Figure 7

Hematoxylin and eosin tissue staining of mice polyps in small intestine, colon, and cecum for control and oxaliplatin treatment groups. Control mice had a higher number of polyps, indicated with red arrows, in the small intestine, colon, and cecum compared with oxaliplatin treatment group. Reproduced from [91] with permission of Elsevier.

Figure 8

Confocal laser scanning microscopy of 5-aminosalycilic acid-loaded chitosan-Ca-ALG microparticles. (a) Fluorescein isothiocyanate-labeled chitosan (green), (b) rhodamine isothiocyanate-labeled ALG (red), and (c) image obtained by superposition. Reproduced from [93] with permission of Elsevier.

Figure 9

SEM micrograph of tandolapril-loaded ALG microparticles. The drug payload was 50% of the dry weight. (a) Microparticles without lactose and (b) microparticles with lactose. Scale bar = 10 μm. Reproduced from [98] with permission of Elsevier.

Figure 10

Morphology of the colloidosomes. (a) SEM and (b) confocal laser scanning microscopy; CaCO₃ microparticles were modified with rhodamine isothiocyanate for red fluorescence visualization. Reproduced from [114] with permission of Elsevier.

Figure 11

Serum glucose concentration after oral administration of insulin-free and insulin-loaded (100 IU/kg) ALG-chitosan microspheres to streptozotocin-induced diabetic rats. Statistically significant difference from insulin-free microspheres: *P < 0.05 and **P < 0.01. Reproduced from [124] with permission of Elsevier.

Figure 12

Oral delivery of pDNA with GFP reporter in ALG microspheres in mice. (a) Flow cytometric analyses showing biodistribution reflected through %GFP-positive cells among various organs 24 and 48 h after the administration of 50 μg and 100 μg pDNA dose. Number of animals for each dose group = 3; total number of mice = 15. (b) Dose-response assessment showing %GFP-positive cells among various mice organs 24 h after the administration of 50 μg, 100 μg, and 150 μg dose. Number of animals for each dose group = 6 (except for 150 μg-dose group which had only 3); total number of mice = 18. All measurements were done in triplicates. Results represent mean ± standard error with the basal levels of expression from negative controls subtracted from expression levels observed in dosed groups. Reproduced from [130] with permission of Elsevier.

Figure 13

Isoniazid-loaded ALG microparticles obtained by a simple emulsion method. Reproduced from [133] with permission of Elsevier.

Figure 14

Production of ALG nanoparticles using liposomal templates. Reproduced and adapted from [156] with permission of the American Chemical Society.

Figure 15

Observed permeate efficiency of bovine serum albumin-loaded TMC nanoparticles, ALG-modified TMC nanoparticles at low (5 mg/mL) and high concentration (20 mg/mL), and control (bovine serum albumin solution) using Caco-2 cell monolayer. Circles indicated permeate efficiency that was significantly higher (P < 0.01) than that of the control. Asterisks indicated permeate efficiency that was significantly higher (P < 0.05) than that of nonmodified TMC nanoparticles. No significant difference was observed between nonmodified and ALG-modified TMC nanoparticles at 5 mg/mL. All data are mean ± S.D. (n = 4). Reproduced from [168] with permission of Elsevier.