Cyclodextrin‐Based Formulations: A Non‐Invasive Platform for Targeted Drug Delivery

Abstract

Cyclodextrins (CDs) are recognized as promising pharmaceutical excipients due to their unique ability to form watersoluble inclusion complexes with various poorly soluble compounds. The numerous investigations on CDs and their use in nanomedicine have received considerable attention in the last three decades, leading to the rapid development of new CD-containing formulations that significantly facilitate targeted drug delivery and controlled drug release, with consequent improvements in drug bioavailability. This MiniReview highlights the efficacy and recent uses of CDs for non-invasive drug delivery. Using ophthalmic and nasal drug delivery as examples, an overview of chemical properties, mechanisms of CDs on drug solubilization, stabilization and permeation, along with their toxicological profiles relevant to nasal and ocular administration, are provided and discussed. The recent development and application of CD-based nanocarrier systems for targeted drug delivery are summarized.Cyclodextrins (CDs) are natural cyclic oligosaccharides that are produced by enzymatic degradation of starch. There are three native CDs designated aCD, bCD and cCD, which are composed of 6, 7 and 8 D-glucopyranose units linked by a-(1, 4) glycosidic, respectively [1]. The molecules are commonly described as truncated cone, bucket-like or donut-shaped, with a hydrophilic outer surface and a relatively hydrophobic inner cavity that allows entrapment of small hydrophobic drug molecules or hydrophobic moieties of larger molecules [2], thereby providing drugs with new physicochemical characteristics without altering their intrinsic properties. Table 1 summarizes the characteristics of different CDs. Natural CDs are preferred for complexation; however, their usability is limited by the small cavity size of aCD, poor aqueous solubility of bCD and low productivity of cCD [3]. Derivatized CDs can be obtained by substituting their hydroxyl groups with desired functional moieties. Methyl-(MebCD and MecCD) [4,5], hydroxypropyl-(HPaCD, HPbCD and HPcCD) [6][7][8] and sulphobutylether (SEBbCD) derivatives [9] are frequently found in pharmaceutical products and have improved solubility and inclusion capacity over natural CDs. Pharmaceutical applications of both natural CDs and their derivatives are common when drug/CD complexes are used to increase drug solubility, improve organoleptic properties [10], enhance drug permeation [11] and increase drug stability, resulting in increased product shelf-life and drug bioavailability [12]. In addition, spontaneous self-assembly of drug/CD complexes into aggregates can lead to innovative drug delivery systems, such as CD-containing liposomes and microspheres as well as microand nanoparticles [13]. Polymerized CDs (e.g. Epi-aCD and Epi-bCD) have also been synthesized to enhance the selfassembly ability of CDs, and to strengthen their interactions with drugs and biological membranes [14]. Compared with other pharmaceutical excipients, CDs have been shown to reduce the toxicity of several drugs and are...

Sulfated β‐Cyclodextrin Templated Assembly and Disassembly of Acridine Orange: Unraveling Contrasting Binding Mechanisms and Light Off/On Switching

“…However, due to its limited aqueous solubility, hemolytic effect and moderate binding ability only towards neutral guests, the uses of βCD in diverse areas are quite restricted ,. To overcome these problems, many derivatives of βCD are being prepared to reduce their toxicity, increase their water solubility and improve their inclusion capabilities for various guest molecules, bringing out their extensive utilizations in supramolecular and suprabiomolecular chemistry ,,,…”

“…Active research in supramolecular chemistry involving efficient water soluble macrocyclic hosts have aroused immense interest in molecular recognition field due to their potential applications in chemotherapy, [1][2][3][4] drug delivery, [5][6][7][8][9][10][11] pharmaceuticals, [10][11][12][13][14][15][16][17][18][19][20] imaging, [21] sensors, [5,[22][23][24][25][26][27] on-off switches, [27][28][29] food industry, [17,30] catalysis, [31,32] nanotechnology, [2,33] functional materials, [33][34][35][36] etc. Supramolecular host-guest assemblies constructed through non-covalent interactions are highly reversible, dynamic and easy to tune by the influence of external stimuli like light, [36][37][38] temperature, [36]…”

“…In supramolecular chemistry, native and derivatized cyclodextrins (CDs) are the most widely investigated host molecules to explore application prospects related to targeted drug delivery, pharmaceutical formulations, improved bioavailability, efficient nanomedicines, etc. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][50][51][52][53][54] and many of these macrocycles are realized as the novel excipients possessing many unexplored potentials. By far, the most extensively used CD homologue is the bCD host.…”

“…[14,55] To overcome these problems, many derivatives of bCD are being prepared to reduce their toxicity, increase their water solubility and improve their inclusion capabilities for various guest molecules, bringing out their extensive utilizations in supramolecular and suprabiomolecular chemistry. [4,11,20,55] Sufated b-cyclodextrin (SCD, cf. Scheme 1) is one of the anionic derivatives of bCD host.…”

Letter from the Editor

“…On the basis of invited MiniReviews published in 2018, the BCPT Young Investigator's Award 2018 went to Chutimon Muankaew from Iceland/Thailand. 2 As long as the financial resources make it possible, the Association for the Publication of BCPT will support scientific meetings in the Nordic countries. Thus, we supported the following events in 2018: Finally, I direct my thanks to all the scientists who continue in increasing numbers to submit their manuscripts to BCPT and to all of the external reviewers who evaluate them very critically.…”