Advanced Healthcare MaterialsVolume 12, Issue 21 2370120 Cover PictureFree Access Efficiency Encapsulation of FK506 with New Dual Self-Assembly Multi-Hydrophobic-Core Nanoparticles for Preventing Keratoplasty Rejection (Adv. Healthcare Mater. 21/2023) Dongmei Wang, Dongmei WangSearch for more papers by this authorBaoshan Huang, Baoshan HuangSearch for more papers by this authorChenchen Zhu, Chenchen ZhuSearch for more papers by this authorLei Wang, Lei WangSearch for more papers by this authorJiahui Jin, Jiahui JinSearch for more papers by this authorJingyang Tan, Jingyang TanSearch for more papers by this authorQing Li, Qing LiSearch for more papers by this authorShengjin Xiang, Shengjin XiangSearch for more papers by this authorKaihui Nan, Kaihui NanSearch for more papers by this authorSen Lin, Sen LinSearch for more papers by this author Dongmei Wang, Dongmei WangSearch for more papers by this authorBaoshan Huang, Baoshan HuangSearch for more papers by this authorChenchen Zhu, Chenchen ZhuSearch for more papers by this authorLei Wang, Lei WangSearch for more papers by this authorJiahui Jin, Jiahui JinSearch for more papers by this authorJingyang Tan, Jingyang TanSearch for more papers by this authorQing Li, Qing LiSearch for more papers by this authorShengjin Xiang, Shengjin XiangSearch for more papers by this authorKaihui Nan, Kaihui NanSearch for more papers by this authorSen Lin, Sen LinSearch for more papers by this author First published: 21 August 2023 https://doi.org/10.1002/adhm.202370120AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Graphical Abstract Dual Self-Assembly In article number 2203242, Kaihui Nan, Sen Lin, and co-workers, report new multi-hydrophobiccore nanoparticles (MHC-NPs) with high encapsulation capacity for hydrophobic agents. MHC-NPs achieve a maximal tacrolimus (also known as FK506)-loading amount of 18%, which is higher than those of previously reported nanocarriers. After being topically administrated, these FK506 MHC-NPs exhibit a better protective effect against immunotoxicity in the corneal grafts after keratoplasty than free FK506 and commercial FK506 eye drop. Volume12, Issue21August 21, 20232370120 RelatedInformation

Nanoparticles self‐assembled by amphiphilic copolymers for loading hydrophobic molecules are intensively investigated. However, their hydrophobic molecule‐loading capacity is low due to the limitation of hydrophobic groups in these copolymers. In this regard, new lysine oligomer‐based multi‐hydrophobic side chain polymers (MHCPs) are synthesized by polymerization of γ ‐benzyl‐ l glutamate N‐carboxy anhydride initiated by side‐chain primary amino groups in lysine oligomer. Each hydrophobic side chain in MHCPs can be self‐assembled by hydrophobic interaction to form multi‐hydrophobic‐core nanoparticles (MHC‐NPs) with silkworm cocoon‐, grape cluster‐, and butterfly‐like shapes (depending on hydrophobic‐side‐chains lengths). To increase their stability, MHC‐NPs are dually self‐assembled with polyethylene glycol–polyglutamic acid through charge interaction. Each hydrophobic core in MHC‐NPs serves as a carrier for hydrophobic molecules, endowing their nanostructure with high loading capacity. MHC‐NPs are employed to load tacrolimus (also known as FK506), and the loading amount is 18% and the loading efficiency is 80%, which are higher than those of previously reported nanomicelles self‐assembled by linear amphiphilic copolymers. Topical administration of FK506‐loaded nanoparticle (FK506‐NP) can significantly prolong retention of FK506 on the eye surface. FK506‐NP exhibits higher in vivo immunosuppressive effects than free FK506 and commercial FK506 eye drop, as well as a better protective effect against immunotoxicity in the corneal grafts after keratoplasty.

Following the traumatic axonal injury in the optic nerve, the failure of retrograde axonal transport to continuously supply neurotrophins from the brain to retina results in deprivation of neurotrophins in retinal ganglion cells (RGCs), which in turn can modulate the fate of RGCs toward apoptosis and thereby impede axon regeneration. In this study, a ciliary neurotrophic factor (CNTF) loaded thermo-sensitive hydrogel was designed and developed as a localized drug depot to restore neurotrophins supply following axon injury. Besides, following traumatic axon injury, overactive immune responses cause neurotoxicity and induce scar formation which together constitutes the major hindrances for axon regeneration. Thus, the FK506, a hydrophobic macrolide immunosuppressant, was co-loaded into the hydrogel after encapsulating it into a polymeric micelle. The materials can undergo sol-to-gel transition within minutes under a physiological pH of 37 °C. The release of drugs from the hydrogel exhibited a sustainable profile in vitro. The optic nerve was exposed by surgical procedure and the animal model was prepared by crushing the nerve with a reverse clamp. For the localized delivery to the optic nerve, a pre-hydrogel liquid containing chitosan, FK506 (in micelle), CNTF, and the gelling agent was directly smeared on the injured site, which gelled under physiological condition. This co-delivery system exhibited in vivo RGCs protective effect against the adverse effects caused by traumatic optic nerve injury, indicating the potential of this drug delivery system for effective optic nerve repair and this strategy may provide promising platforms for localized drug delivery in various other therapies.

Chitosan (CS) based nanoparticles (NPs) have several advantages in delivering drugs. They are usually prepared in a micro-emulsion solvent system but this route can leave significant levels of potentially harmful organic solvent residue in the NPs. In this study, we prepared CS based nanocomposites using charge driven self-assembly in an aqueous buffer, thus avoiding the use of organic solvents. Doxorubicin (DOX) was covalently attached to positive charged CS with a legumain substrate peptide to confer targeted drug release property, since legumain is often overexpressed in tumors or tumor associated micro environments. This DOX prodrug solution interacted with negative charged methoxyl poly (ethylene glycol)-block-poly (glutamic acid) copolymer (PEG-PGA) in an aqueous buffer forming nanocomposite with a regular morphology. The particle size and zeta potential of these NPs was regulated by the addition of different PEG–PGA concentrations into the DOX prodrug solution. Due to its potential for legumain triggered release, this DOX NP exhibited enhanced cytotoxicity against choroidal melanoma cell line (Mum-2C) and reduced cytotoxicity on normal human corneal epithelial cells (HCEC), suggesting a good potential for enhanced targeted delivery of chemotherapeutic agents.