Polysaccharide-Based Drug Carriers-A Patent Analysis

Abstract

Polysaccharide-based carriers as biomaterials for drug delivery have been inspiring scientists for years due to their exceptional characteristics, such as nontoxicity, biocompatibility, and degradability, as they are able to protect pharmaceutically active molecules and provide their controlled/modified release. This review focuses on selected drug delivery systems based on natural polymers, namely fucoidan, pullulan, dextran, and pectin, with the aim of highlighting published patent documents. The information contained in patents is very important because it is usually not published in any other document and is much less discussed as the state of the art in the scientific literature. The Espacenet-European Patent Office database and the International Patent Classification were used for the research to highlight the specific search procedure. The presented analysis of the innovative state of the art includes an overview from the first patent applications to the latest granted patents in this field.

Keywords: dextran; drug delivery system; fucoidan; gels; pectin; pullulan.

Figure 1

Drug carriers based on polysaccharide gels and derivatives thereof (e.g., gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar, or pectin): yearly and cumulative patent applications and granted patents numbers in dependence on the earliest priority date (from 1929 to 2024), the IPC subgroups, applicants, and countries for granted patents. Two-letter codes: CN, WO, US, EP, KR, CA, and AU are abbreviations for the following: Republic of China, the international publication of patent application using the Patent Cooperation Treaty (PCT) of the World Intellectual Property Organization (WIPO), United States of America, European Patent, Japan, Republic of Korea, Canada, and Australia, respectively. Data were obtained from the Espacenet database [14].

Figure 2

Proposed mechanism responsible for fucoidan bioactivity: (A) macrophage activation by fucose-containing sulfated polysaccharides (FCSPs) as mediated through specific membrane receptor activation, namely Toll-like receptor-4, cluster of differentiation 14, competent receptor-3, and scavenging receptor, which in turn induce intracellular signaling via mitogen-activated protein kinases (MAPKs); (B) activation of macrophages lead to the production of cytokines such as interleukins (ILs) IL-12 and IL-2 and interferon-gama (IFN-γ), which enhance natural killer (NK) cell activation that may stimulate T-cell activation further via IFN-γ. Reprinted from ref. [42] under open access creative commons CC-BY license.

Figure 3

Fucoidan: cumulative and yearly numbers of patent applications and granted patents depending on the earliest priority date (from 1962 to 2024), the IPC and CPC subgroups, the first eight applicants, and countries for granted patents. Two-letter codes: KR, US, JP, CN, TW, AU, CH, NL, FR, and SE are abbreviations for the following: the Republic of Korea, United States of America, Japan, Republic of China, Taiwan Province of China, Australia, Switzerland, Netherland, France, and Sweden, respectively. Data were obtained using the Espacenet database [14].

Figure 4

Structural formula of fucoidan homopolysaccharide from brown algae Sargassum, according to data presented in granted patent CN117247472B [51].

Figure 5

The main structure of the sea cucumber fucoidan, derived from Aegean sea cucumber Holothuria polii, according to data presented in granted patent CN110437288B [63].

Figure 6

(A) Optical images with dextran (Dx)-based cryogels prepared without SBE (sample DxCG6) and with SBE (sample DxCG7); (B) schematic representation of the Dx cross-linking with EGDGE and the interactions through hydrogen bonding between SBE and Dx matrix. Reprinted from ref. [87] under open access creative commons CC-BY license.

Figure 7

Dextran: cumulative and yearly numbers of patent applications and granted patents depending on the earliest priority date (from 1949 to 2024), the IPC subgroups, the first eight applicants, and countries for granted patents. Two-letter codes: US, KR, CN, JP, CH, DE, GB, DK, and TW are abbreviations for the following: United States of America, Republic of Korea, Republic of China, Japan, Switzerland, Germany, Great Britain, Denmark, and Taiwan Province of China, respectively. Data were obtained using the Espacenet database [14].

Figure 8

The structural unit of pullulan (maltotriose (α-1,4-triglucoside) interconnected by α-(1→6) glycosidic bonds), according to data presented in granted patent EP1363951B1 [100].

Figure 9

Chitosan-oxidized pullulan hydrogels loaded with essential clove oil: synthesis, characterization, antioxidant, and antimicrobial properties—graphical abstract. Reprinted from ref. [111] under open access creative commons CC-BY license.

Figure 10

Pullulan: cumulative and yearly numbers of patent applications and granted patents depending on the earliest priority date (from 1953 to 2024), the IPC subgroups, the first eight applicants, and countries for granted patents. Two-letter codes: KR, US, JP, CN, DE, CH, FR, GB, TW, and DK are abbreviations for the following: Republic of Korea, United States of America, Japan, Republic of China, Germany, Switzerland, France, Great Britain, Taiwan Province of China, and Denmark, respectively. Data were obtained using the Espacenet database [14].

Figure 11

(a) Schematic diagram of various pectin structures: HG-homogalacturonan (the “smooth” region of α-(1,4)-linked D-galacturonic acid residues with methyl and acetyl esterification), RG-I—rhamnogalacturonan I (“hairy” region with alternating L-Rha and D-GalA residues and variable side chains) and RG-II—rhamnogalacturonan II (a complex structure containing up to 13 different sugars and 21 glycosidic linkages); (b) the “egg-box” model illustrating the gelling mechanism of low-methoxyl pectin. Reprinted from ref. [130] under open access creative commons CC-BY license.

Figure 12

Pectin: cumulative and yearly numbers of patent applications and granted patents depending on the earliest priority date (from 1903 to 2024), the IPC subgroups, the first eight applicants, and countries for granted patents. Two-letter codes: US, KR, CN, GB, CH, DE, DK, JP, CA, IN, and are abbreviations for the following: United States of America, Republic of Korea, Republic of China, Great Britain, Switzerland, Germany, Denmark, Japan, Canada, and India, respectively. Data were obtained using the Espacenet database [14].