Gene transfer to rat cerebral cortex mediated by polysorbate 80 and poloxamer 188 nonionic surfactant vesicles

Abstract

BackgroundGene therapy can be an intriguing therapeutic option in wide-ranging neurological disorders. Though nonviral gene carriers represent a safer delivery system to their viral counterparts, a thorough design of such vehicles is crucial to enhance their transfection properties.PurposeThis study evaluated the effects of combined use of two nonionic surfactants, poloxamer 188 (P) and polysorbate 80 (P80) into nanovesicles – based on 2,3-di(tetradecyloxy)propan-1-amine cationic lipid (D) – destined for gene delivery to central nervous system cells.MethodsNiosome formulations without and with poloxamer 188 (DP80 and DPP80, respectively) were prepared by the reverse-phase evaporation technique and characterized in terms of size, surface charge, and morphology. After the addition of pCMS-EGFP plasmid, the binding efficiency to the niosomes was evaluated in agarose gel electrophoresis assays. Additionally, transfection efficiency of complexes was also evaluated in in vitro and in vivo conditions.ResultsIn vitro experiments on NT2 cells revealed that the complexes based on a surfactant combination (DPP80) enhanced cellular uptake and viability when compared with the DP80 counterparts. Interestingly, DPP80 complexes showed protein expression in glial cells after administration into the cerebral cortices of rats.ConclusionThese data provide new insights for glia-centered approach for gene therapy of nervous system disorders using cationic nanovesicles, where nonionic surfactants play a pivotal role.

Gene delivery to the rat retina by non-viral vectors based on chloroquine-containing cationic niosomes

“…In that study, the DTPA cationic lipid (non-salt form) succeeded to transfect retinal cells in vitro conditions [11], while in such mentioned study, the salt form failed to transfect retinal cells in vivo. Interestingly, the same formulation with the same salt form of cationic lipid (DPP80) succeeded to transfect cerebral cortical cells in vivo [28]. Strikingly, both salt/non-salt forms of the cationic lipid were able to transfect ARPE-19 cells in vitro conditions.…”

Cationic niosome-based hBMP7 gene transfection of neuronal precursor NT2 cells to reduce the migration of glioma cells in vitro

“…In our recent study [11], we developed a novel cationic niosome gene carrier based on chemical compounds (the cationic lipid 2,3-ditetradecyloxypropan-1amine, the non-ionic surfactants poloxamer 188 and polysorbate 80) demonstrating flattering properties for gene delivery applications [12]. Our previous results obtained with reporter GFP plasmids, in vitro/vivo, have encouraged us to proceed with the current study in which we aimed to provide a proof-of-concept of whether NT2 cells could be used as a model for hBMP7 gene expression in order to combat glioma cell migration.…”

Niosome-Based Approach for In Situ Gene Delivery to Retina and Brain Cortex as Immune-Privileged Tissues

“…Non-ionic surfactants can be classified into four different categories: alkyl ethers, alkyl esters, alkyl amides, and esters of fatty acids [73]. Some non-ionic surfactants that have been used in niosomes designed for gene delivery applications include polyoxyethylene alkyl ether (Brij © [73]), polysorbates (Tween © [80]), sorbitan fatty acid esters (Span © [81]), or poloxamers [82]. The most relevant parameters of non-ionic surfactants to consider are the hydrophilic/lipophilic balance (HLB), which can be used as a "saving guide" parameter to select the appropriate surfactant [83], the critical packing parameter (CPP), which plays an important role in the vesicular-forming ability of niosomes [84], or the gel liquid transition temperature (T C ), which has a relevant impact on the drug entrapped efficiency [85].…”

“…Considering the previously reported properties of poloxamer 188 regarding biocompatibility and capacity to protect neurons against brain injury [160], its incorporation into niosomes based on the hydrochloride salt of 2,3-di(tetradecyloxy)propan-1-amine cationic lipid and polysorbate 80 surfactant was evaluated [82]. Therefore, two niosome formulations that differed only regarding the presence or absence of the non-ionic surfactant poloxamer 188 were elaborated by the reverse-phase evaporation technique and characterized to deliver the genetic material into the rat brain cortex.…”