Bioadhesive Polymersome for Localized and Sustained Drug Delivery at Pathological Sites with Harsh Enzymatic and Fluidic Environment via Supramolecular Host–Guest Complexation

Abstract

Targeted and sustained delivery of drugs to diseased tissues/organs, where body fluid exchange and catabolic activity are substantial, is challenging due to the fast cleansing and degradation of the drugs by these harsh environmental factors. Herein, a multifunctional and bioadhesive polycaprolactone-β-cyclodextrin (PCL-CD) polymersome is developed for localized and sustained co-delivery of hydrophilic and hydrophobic drug molecules. This PCL-CD polymersome affords multivalent crosslinking action via surface CD-mediated host-guest interactions to generate a supramolecular hydrogel that exhibits evident shear thinning and efficient self-healing behavior. The co-delivery of small molecule and proteinaceous agents by the encapsulated PCL-CD polymersomes enhances the differentiation of stem cells seeded in the hydrogel. Furthermore, the PCL-CD polymersomes are capable of in situ grafting to biological tissues via host-guest complexation between surface CD and native guest groups in the tissue matrix both in vitro and in vivo, thereby effectively extending the retention of loaded cargo in the grafted tissue. It is further demonstrated that the co-delivery of small molecule and proteinaceous drugs via PCL-CD polymersomes averts cartilage degeneration in animal osteoarthritic (OA) knee joints, which are known for their biochemically harsh and fluidically dynamic environment.

Effects of tetrahedral framework nucleic acid/wogonin complexes on osteoarthritis

“…[27][28][29][30] Compared to various nanochemical polymers (upconversion nanotransducer-based nanocomplexes, nanocomposite hydrogels, or supramolecular hydrogels), TFNA not only possesses good biocompatibility and biodegradability and the ability to permeate cells but can also be functionalized via modification with DNA fragments, RNAs, polypeptide monomers, and small-molecule drugs. [31][32][33][44][45][46] In our previous studies, we found that TFNA can enhance the proliferation and migration of chondrocytes and maintain their morphology at an optimum concentration of 250 nmol·L −1 . 21,22 Upon consideration of these characteristics, TFNA was used in combination with wogonin, a naturally occurring flavonoid with various biological properties, such as anti-inflammatory and anti-cancer activity.…”

Stimuli‐Responsive Release of Antimicrobials Using Hybrid Inorganic Nanoparticle‐Associated Drug‐Delivery Systems

“…Polymersomes are self‐assembling artificial vesicles comprised of an enclosed bilayer membrane formed using amphiphilic block copolymers . The polymers forming the bilayer shell structure typically have three block copolymer variations, including a diblock copolymer AB and two triblock variants, ABA and ABC, where A and C represent distinct hydrophilic polymers and B represents a hydrophobic polymer …”

Tailoring Gelation Mechanisms for Advanced Hydrogel Applications

“…Noncovalent interactions between complementary groups -Mixing-induced two-component hydrogels [53] -DNA-PNA methacrylamide hydrogels [72] -DNA-polypeptide hydrogels [73] -Enantiomer-functionalized dextran hydrogels [74] -Host-guest cyclodextrin hydrogels [76] -Cucurbit[n]uril hydrogels [77] Covalent crosslinking -Gelatin-based hydrogels [11,55,63] -Collagen-based hydrogels [54] -Fibrinogen-based hydrogels [56] -Chitosan-based hydrogels [57] -Alginate-based hydrogels [64] -HA-based hydrogels [65,66] -PEG-based hydrogels [58,[60][61][62]66,67,[69][70][71] Nanoparticle-based -Methylcellulose-based hydrogels [78,79] -HA-based hydrogels [79,82] -PEG-based hydrogels [80,81,84] -DNA-based hydrogels [83] Change in pH…”

“…Host-guest hydrogel networks have also been formed through the complexation of adamantane-functionalized polymersomes and HA modified with β-cyclodextrins. [82] A similar approach can be taken using DNA hybridization, for example, hydrogel networks have been assembled from six-arm DNA strands annealed with complementary DNA sequences bound to various gold nanostructures. [83] More recently, hydrogels have been assembled using coordinate covalent bonds formed between carboxylated magnetic iron oxide nanoparticles and catechol-functionalized polymer chains.…”