Investigation of the Interface in Silica-Encapsulated Liposomes by Combining Solid State NMR and First Principles Calculations

Abstract

In the context of nanomedicine, liposils (liposomes and silica) have a strong potential for drug storage and release schemes: such materials combine the intrinsic properties of liposome (encapsulation) and silica (increased rigidity, protective coating, pH degradability). In this work, an original approach combining solid state NMR, molecular dynamics, first principles geometry optimization, and NMR parameters calculation allows the building of a precise representation of the organic/inorganic interface in liposils. {(1)H-(29)Si}(1)H and {(1)H-(31)P}(1)H Double Cross-Polarization (CP) MAS NMR experiments were implemented in order to explore the proton chemical environments around the silica and the phospholipids, respectively. Using VASP (Vienna Ab Initio Simulation Package), DFT calculations including molecular dynamics, and geometry optimization lead to the determination of energetically favorable configurations of a DPPC (dipalmitoylphosphatidylcholine) headgroup adsorbed onto a hydroxylated silica surface that corresponds to a realistic model of an amorphous silica slab. These data combined with first principles NMR parameters calculations by GIPAW (Gauge Included Projected Augmented Wave) show that the phosphate moieties are not directly interacting with silanols. The stabilization of the interface is achieved through the presence of water molecules located in-between the head groups of the phospholipids and the silica surface forming an interfacial H-bonded water layer. A detailed study of the (31)P chemical shift anisotropy (CSA) parameters allows us to interpret the local dynamics of DPPC in liposils. Finally, the VASP/solid state NMR/GIPAW combined approach can be extended to a large variety of organic-inorganic hybrid interfaces.

A molecular dynamics study of the effects of fast molecular motions on solid-state NMR parameters

“…16 Fast, small-amplitude motions have a much more subtle effect on NMR parameters. Here molecular dynamics (MD) or Monte Carlo simulations provide a general approach for determining how NMR parameters, including relaxation times, 17 are affected by motion.…”

Silica-coated flexible liposomes as a nanohybrid delivery system for enhanced oral bioavailability of curcumin

“…This was further explained by stabilizing effects achieved through the presence of water molecules located between the head groups of the phospholipids and the silica surface, forming an interfacial H-bonded water layer. 30 The silica shell formation can be obtained by either a prehydrolysis or a hydrolysis process of the inorganic precursor TEOS, according to methods described in the literature. While the former process includes a preliminary 48-hour hydrolysis of TEOS before incubation with liposomes for another 72 hours, the latter is based on a synchronous process of precursor hydrolysis and surface precipitation for 60 hours.…”

Liposil Nanocarriers for Pharmaceutical Applications: Synthesis Innovations

“…Silica precursor molecules hydrolyze, yielding a sol, and then condense, to form a gel able to establish hydrogen-like/electrostatic bounding to the inner liposome structure. The silica-coating helps maintaining the aqueous interior in the liposome-core [6,[8][9][10][11][12], and improves the bioavailability of poorly water soluble drugs by enhancing their colloidal stability, retaining, at the same time, the liposome intrinsic advantage as drug carrier. Liposil were reported by Bégu et al [8] for the first time.…”

“…Until now, Liposil structures are difficult to produce due to large time-consuming coating protocols [6,[8][9][10][11][12]. Bégu et al [8] hydrolyze tetraethyl orthosilicate (TEOS) in phosphate-buffered saline solution (PBS), for two days long.…”

“…In the second Liposil set, the core is formed by negatively charged liposomes of 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine (DMPC) and 1,2-Dimyristoyl-sn-Glycero-3-Phosphoglycerol (DMPG), with DMPC:DMPG molar ratio of 7:3. So far only neutral liposomes were described in literature [6,[8][9][10][11][12] when Liposils are concerned. polycarbonate membranes, with pores ranging from 800 nm down to 100 nm.…”