Liposomes are one of the vital generally used drug supply methods, and several other formulations have been efficiently translated into scientific functions [1], [2], [3], [4], [5]. Owing to their distinctive structure, liposomes can encapsulate each hydrophilic and hydrophobic therapeutic brokers and possess good biocompatibility [6]. Hydrophilic medication, resembling doxorubicin, are usually entrapped throughout the aqueous compartment by energetic loading applied sciences to attain excessive encapsulating effectivity [1], [7], [8]. In distinction, hydrophobic medication, resembling paclitaxel (PTX), are integrated into the hydrophobic area of the lipid bilayer [9], [10], [11]. Nevertheless, this encapsulation technique can disrupt bilayer integrity and lipid packing, speed up drug leakage, thereby undermining liposome stability and the therapeutic efficacy [12], [13], [14]. Given {that a} substantial proportion of present drug candidates show poor aqueous solubility [15], creating methods to enhance the effectivity and stability of hydrophobic drug loading in liposomes is of vital significance.
To handle these challenges, a wide range of methods have been developed, which could be broadly labeled into three classes. 1) Optimization of lipid composition to modulate membrane properties. For instance, incorporating unsaturated or lyso-lipids creates “pockets” throughout the hydrophobic bilayer that facilitate paclitaxel encapsulation [10]. Equally, medium or lengthy chain triglycerides can regulate the fluidity and lamellarity of saturated PC-based liposomes, thereby enhancing paclitaxel loading effectivity [16]. 2) Structural modification of phospholipids. Rising phospholipid acyl chain size enhances the entrapment of hydrophobic bacteriocins micrococcin P1, however compromises liposome stability [17]. 3) Prodrug modification of hydrophobic brokers. For instance, introducing an aminoacyl substituent on the 2′-hydroxyl group converts docetaxel right into a pH-responsive prodrug that’s steady beneath acidic situations however hydrolyzed at greater pH, enabling energetic loading into the aqueous core through a transmembrane proton gradient [18]. Alternatively, PTX could be conjugated with phospholipids to extend loading capability [19] or chemically modified to permit energetic loading [20]. Regardless of these advances, the aforementioned methods typically require laborious screening of lipid formulations or prodrug candidates, and chemical modifications are typically relevant solely to particular compounds.
One other consideration for liposomes and drug nanocarriers generally is the formation of protein corona. As soon as uncovered to blood circulation, the floor of liposomes is quickly coated with serum proteins, which considerably impacts the floor properties and is expounded to the clearance of liposomes [21], [22], [23]. The adsorption of protein corona might disrupt the integrity of lipid bilayer and set off payload leakage [24], [25], [26]. Since hydrophobic medication are loaded within the lipid bilayer, they’re vulnerable to be affected by the destabilization of lipid bilayer. Because of this, the environment friendly and steady encapsulation of hydrophobic brokers in liposomes stays problematic.
Our earlier work pioneered nanobowl-supported liposomes (NbLipo) as a easy but efficient technique to scale back hydrophilic drug leakage in blood circulation attributable to plasma protein and blood stream shear pressure [27]. On this work, we exhibit for the primary time that embedding nanobowl throughout the aqueous cavity of liposomes markedly improves the encapsulation effectivity and loading stability of hydrophobic agent (PTX). This enchancment is attributed to nanobowl-induced membrane stabilization, as evidenced by decreased fluidity and elevated rigidity [28], [29]. Proteomic evaluation additional reveals that such structural stabilization diminishes total protein corona adsorption in serum. Unexpectedly, nanobowl help additionally results in important enrichment of CD55, a complement inhibitor [30], [31], [32], [33], and downregulation of enhances C3 and C5 on the floor of NbLipo, thereby contributing to diminished blood clearance. Due to this fact, NbLipo facilitates improved PTX supply and superior antitumor efficacy in contrast with standard liposomes (Lipo) (Scheme 1). Collectively, these findings set up NbLipo as a strong platform to beat the intrinsic loading instability of hydrophobic drug loaded liposomes, thereby increasing the therapeutic potential of liposomal carriers.