Self-assembled supramolecular hydrogels based on polymer–cyclodextrin inclusion complexes for drug delivery

Abstract

A supramolecular system is composed of two or more molecular entities held together and organized by means of intermolecular non-covalent binding interactions [1]. Supramolecular structures involving macrocyclic compounds have attracted tremendous interest not only as models for understanding natural supramolecular self-assembly and molecular recognition, but also as precursors for designing novel nanomaterials for electronics, biomedical and pharmaceutical applications [2][3][4][5][6][7][8][9][10][11]. Cyclodextrins (CDs), a series of natural cyclic oligosaccharides composed of 6, 7 or 8 d(+)-glucose units linked by d(+)-1,4-linkages (termed α-, β-and γ-CD, respectively), are well-suited for use in supramolecular systems. Th e geometry of CDs produces a hydrophobic inner cavity with a depth of ca. 7.0 Å and an internal diameter of ca. 4.5, 7.0 or 8.5 Å (α-, β-and γ-CD, respectively). Various molecules can be inserted into the cavities of CDs to form supramolecular inclusion complexes, and such systems have been studied extensively as models for understanding the mechanism of molecular recognition [12][13][14][15][16].A three-dimensional crosslinked network formed from a hydrophilic polymer, referred to as a hydrogel, can retain large volumes of water, causing the network to swell in solution. Th e extent of swelling and the content of water retained are largely dependent on the hydrophilicity of the polymer chains and the crosslinking density. Th e crosslinks can be formed by either covalent bonds or physical cohesion forces between the polymer segments, such as ionic bonds, hydrogen bonds, van der Waals forces and hydrophobic interactions [17][18][19][20]. Polymeric hydrogels are of great interest for biomaterials applications because of their biocompatibility [21,22], and due to their high water content, they are attractive for the delivery of delicate bioactive agents such as proteins [18,23,24]. For example, chemically crosslinked poly(ethylene oxide) (PEO) hydrogels have been studied extensively for this purpose [25][26][27]. However, requiring covalent crosslinking for gelation, many hydrogels can only be applied as implantables, and the incorporation of drugs by sorption may be time-consuming and provide only limited loading potential. For drug delivery, the crosslinking reaction may also conjugate the drug to the hydrogel or impair the drug's chemical integrity, while the hydrogel itself may become nonbiodegradable with an ill-defi ned composition. A delivery formulation in which gelation and drug loading can be achieved simultaneously in an aqueous environment and without covalent crosslinking is therefore an attractive prospect. Self-assembled supramolecular hydrogels based on polymer-cyclodextrin inclusion complexes for drug deliveryJun Li * National University of Singapore, SingaporeThe supramolecular self-assembly of cyclodextrins (CDs) and polymers has led to the development of novel supramolecular hydrogels for drug delivery applications. Many diff erent supramolecular hydrogels have been formed ...

In situ crosslinkable hydrogels for engineered cellular microenvironments

“…Самоорга-низующиеся инъекционные гидрогели образуют-ся путем взаимодействия циклодекстринов (CDs), природных циклических олигосахаридов, состоя-щих из 6, 7, 8 D-глюкопиранозидных единиц (a, b, r-CD) [15]. Эти молекулы формируют гидрофобную внутреннюю полость с последующим образовани-ем комплекса с гостевыми молекулами, такими как адамантин (Ad), ПЭГ и холестерины [16][17][18]. Были разработаны новые с низкой вязкостью самоорга-низующиеся инъекционные гидрогели с помощью взаимодействия «хозяин-гость» с использованием Ad и CD [19].…”

“…The self-assembling injectable hydrogels are formed through the interaction of the cyclodextrins (CDs), natural cyclic oligosaccharides composed of 6, 7, 8 D-glucopyranoside units (a, b, r-CD) [15]. These molecules include a hydrophobic inner cavity that induces an inclusion complex with other guest molecules such as adamantine (Ad), PEG, and cholesterols [16][17][18]. Christopher et al developed novel shear thinning and self-assembling injectable hydrogels through hostguest interaction using Ad and CDs [19].…”

Synthetic Strategies towards Silica/Poly (Acrylamide-Co-Acrylic Acid) Composites

“…A three-dimensional cross linked system is formed from a hydrophilic polymer, referred to as a hydrogels, which swells and absorbs water causing the network to swell in solution [18]. Polymeric hydrogels are of great interest for biomaterials applications because of their biocompatibility [19].…”

A biodegradable thermo-responsive hybrid hydrogel: therapeutic applications in preventing the post-operative recurrence of breast cancer

“…Adjuvant traditional chemotherapy, endocrine therapies and radiotherapy are the main methods used to reduce the risk of relapse in breast cancer patients. [12][13][14][15][16] However, alternatives with lower toxicities and side effects remain urgently needed.…”

“…Hydrogels can undergo intelligent three-dimensional structural changes in response to environmental stimuli such as temperature, pH, light and electrical fields. [16][17][18][19] Hydrogels exhibit great potential for the local delivery of drugs, including small molecules and therapeutic proteins. 20,21 Near-infrared (NIR) light is a relatively safe external stimulus that is able to penetrate several centimeters of human soft tissue with minimal damage.…”