Design and Synthesis of Lipidic Organoalkoxysilanes for the Self‐Assembly of Liposomal Nanohybrid Cerasomes with Controlled Drug Release Properties

Abstract

This paper reports the facile design and synthesis of a series of lipidic organoalkoxysilanes with different numbers of triethoxysilane headgroups and hydrophobic alkyl chains linked by glycerol and pentaerythritol for the construction of cerasomes with regulated surface siloxane density and controlled release behavior. It was found that the number of triethoxysilane headgroups affected the properties of the cerasomes for encapsulation efficiency, drug loading capacity, and release behavior. For both water-soluble doxorubicin (DOX) and water-insoluble paclitaxel (PTX), the release rate from the cerasomes decreased as the number of triethoxysilane headgroups increased. The slower release rate from the cerasomes was attributed to the higher density of the siloxane network on the surface of the cerasomes, which blocks the drug release channels. In contrast to the release results with DOX, the introduction of one more hydrophobic alkyl chain into the cerasome-forming lipid resulted in a slower release rate of PTX from the cerasomes due to the formation of a more compact cerasome bilayer. An MTT viability assay showed that all of these drug-loaded cerasomes inhibited proliferation of the HepG2 cancer cell line. The fine tuning of the chemical structure of the cerasome-forming lipids would foster a new strategy to precisely regulate the release rate of drugs from cerasomes.

Advancing the Pharmaceutical Potential of Bioinorganic Hybrid Lipid‐Based Assemblies

“…CFSLs 4 is a biodegradable phospholipid with triethoxysilyl headgroup, which provide improved biocompatibility. CFSLs 5 and 6 bearing two to three triethoxysilyl heads were synthesized to tune the siloxane network on the surface of cerasomes 43. The drug release rate decreased as the number of triethoxysilyl headgroups in CFSLs increased 32.…”

“…The drug release rate decreased as the number of triethoxysilyl headgroups in CFSLs increased 32. CFSLs 7 has one triethoxysilyl headgroup but three alkyl chains, which endows higher entrapment efficiency for hydrophobic drugs due to more compact bilayer structure 43. CFSLs 8 containing a disulfide bond provides glutathione‐responsiveness for controlled release 44.…”

 Progress of Liposomal Nanohybrid Cerasomes as Novel Drug Nanocarriers

“…Afterwards, numerous morphologically stable cerasomes have been fabricated by employing various artificially designed cerasome-forming lipids (CFL). [23] As shown in Figure 1, CFL consists of a hydrophilic triethoxysilyl head moiety, a hydrophobic alkane chain segment and a connector unit between them. [25] When the triethoxysilyl groups are hydrolyzed to form silanol groups under appropriate conditions, cerasome-forming lipids become amphiphilic molecules, followed by self-assembly to form lipid bilayer vesicles.…”

“…[28] Meanwhile, the drug release rate from cerasomes could be precisely controlled by artificially tuning the chemical structure of cerasomes-forming lipids, such as adjusting the numbers of triethoxysilane headgroups and hydrophobic alkyl chain ( Figure S1 in Supporting Information). [36] In addition, external stimuli (i.e, pH, [31] temperature, [37,38] and light [39,40] ) have been exploited to control drug release from cerasomes at the desired location and time. These results demonstrate the potential for cerasomes to serve as effective controlled-release drug carriers.…”

“…[22] Besides, cerasomes have better biocompatibility than silica nanoparticles with similar size due to the presence of liposomal structure. [23] Cerasomes integrate the advantages of both liposomes and silica nanoparticles but overcome their shortings. In addition, cerasomes can encapsulate a wide range of drug molecules and the silanols on the surface make it convenient for cerasomes to be functionalized to effectively delivery drugs to desired areas via silanecoupler chemistry.…”