title: Fabrication of an ionic-sensitive in situ gel loaded with resveratrol nanosuspensions intended for direct nose-to-brain delivery.
abstract: The objective of this study was to fabricate a composite in situ gelling formulation combining nanoparticulates and an ionic-triggered deacetylated gellan gum (DGG) matrix for challenging intranasal drug delivery. The prepared resveratrol nanosuspensions (Res-NSs) were distributed in DGG solutions. Parameters such as the in situ gelation capability, particle size, rheological properties, and texture profiles were used to describe the properties of the in situ gel. Pharmacokinetic and brain-targeting efficiency studies were performed after intranasal and intravenous administration, respectively. Biodistribution and localization using in vivo imaging systems and fluorescence microscopy are also described. The formulation containing 0.6% w/v DGG displayed a favorable gelling ability and the desired viscosity. The rheology results established that the DGG in situ gel possesses the characteristics of shear thinning, thixotropy and yield stress. The results of the textural profile revealed an increase in adhesiveness and viscosity for the in situ gel compared to the DGG solution. In vitro penetration studies followed a Higuchi mathematic model. Pharmacokinetics revealed a 2.88-times increase of bioavailability in the brain by intranasal Res-NSs in situ gel formulation. The drug targeting efficiency (458.2%) and direct transport percentages (78.18%) demonstrated direct delivery via the nose-brain pathway. The distribution and localization further illustrated the existence of direct nose-to-brain transport, bypassing the BBB. In sum, this hybrid in situ gel system is a promising approach for intranasal application in terms of the enhancement of nasal mucosal permeability and increased nasal cavity residence time by a nanotechnology delivery system and in situ gelling technology.
authors: College of Pharmacy, Taishan Medical University, Taian 271016, PR China. Electronic address: haojifu@163.com.
authors: Jifu
authors: J
authors: Hao
authors: College of Pharmacy, Taishan Medical University, Taian 271016, PR China.
authors: Jing
authors: J
authors: Zhao
authors: Pathology Department, Taishan Medical University Affiliated Hospital, Taian 271016, PR China.
authors: Shupeng
authors: S
authors: Zhang
authors: College of Pharmacy, Taishan Medical University, Taian 271016, PR China.
authors: Tiantian
authors: T
authors: Tong
authors: College of Pharmacy, Taishan Medical University, Taian 271016, PR China.
authors: Qiannan
authors: Q
authors: Zhuang
authors: College of Pharmacy, Taishan Medical University, Taian 271016, PR China.
authors: Kai
authors: K
authors: Jin
authors: College of Pharmacy, Taishan Medical University, Taian 271016, PR China.
authors: Wei
authors: W
authors: Chen
authors: College of Pharmacy, Taishan Medical University, Taian 271016, PR China. Electronic address: tanghuazhang218@163.com.
authors: Hua
authors: H
authors: Tang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics; D001682:Biological Availability; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D005782:Gels / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009297:Nasal Mucosa / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013535:Suspensions; D014018:Tissue Distribution; D014783:Viscosity
chemical_list: D000975:Antioxidants; D004337:Drug Carriers; D005782:Gels; D013267:Stilbenes; D013535:Suspensions; D000077185:Resveratrol
keywords: Gellan gum; In situ gel; Intranasal drug delivery; Resveratrol