Radio Frequency-Activated Nanoliposomes for Controlled Combination Drug Delivery

Abstract

Abstract. This work was conducted in order to design, characterize, and evaluate stable liposomes containing the hydrophobic drug raloxifene HCl (RAL) and hydrophilic doxycycline HCl (DOX), two potentially synergistic agents for treating osteoporosis and other bone lesions, in conjunction with a radio frequency-induced, hydrophobic magnetic nanoparticle-dependent triggering mechanism for drug release. Both drugs were successfully incorporated into liposomes by lipid film hydration, although combination drug loading compromised liposome stability. Liposome stability was improved by reducing the drug load and by including Pluronics® (PL) in the formulations. DOX did not appear to interact with the phospholipid membranes comprising the liposomes, and its release was maximized in the presence of radio frequency (RF) heating. In contrast, differential scanning calorimetry (DSC) and phosphorus-31 nuclear magnetic resonance ( 31 P-NMR) analysis revealed that RAL developed strong interactions with the phospholipid membranes, most notably with lipid phosphate head groups, resulting in significant changes in membrane thermodynamics. Likewise, RAL release from liposomes was minimal, even in the presence of RF heating. These studies may offer useful insights into the design and optimization of multidrug containing liposomes. The effects of RAL on liposome characteristics and drug release performance underscore the importance of appropriate physical-chemical analysis in order to identify and characterize drug-lipid interactions that may profoundly affect liposome properties and performance early in the formulation development process.

Lipid-Based Antimicrobial Delivery-Systems for the Treatment of Bacterial Infections

“…Accordingly, liposomes can have widely different properties and for the purpose of infection-control (i.e., interaction with negatively-charged bacterial cell surfaces; Nederberg et al, 2011;Ng et al, 2013), it is relevant to classify them into natural lipid-based, cationic, anionic, zwitterionic liposomes, and fusogenic liposomes. Diameter and diameter distribution are the most important factors for in vivo use of liposomes (Malekar et al, 2015) and in order to prevent rejection by the reticulo-endothelial system (Wang et al, 2019) and allow penetration through water channels (Greiner et al, 2005) in infectious biofilms, liposomes for infection-control should preferentially have diameters that maximally range up to 100-200 nm (Liu et al, 2019a). Therefore, we will now confine this review to smaller liposomes with diameters of maximally 200 nm and briefly summarize the physico-chemistry underlying these liposomes.…”

Hybrid lipid–nanoparticle complexes for biomedical applications

“…48 The same hybrid is further investigated for its ability to co-release hydrophobic raloxifene HCl (RAL) residing in bilayer and doxycycline HCl (DOX) residing in aqueous core of the liposomes. 52 Exposure to AMFs triggers the significant release of DOX, however, RAL release is limited due to its high affinity for the lipid bilayer. Amstad et al aimed to improve the stability of these hybrids by PEGylating the liposomes and moving on from oleic acid-capped SPIONs in favour of palmityl-nitroDOPA-capped SPIONs that are less prone to aggregation and more easily integrated into liposome bilayers than oleic acid-capped SPIONs.…”

Pulse Magnetic Fields Induced Drug Release from Gold Coated Magnetic Nanoparticle Decorated Liposomes

“…The drug carrier is expected to be released from the liposome via passive or active stimuli [8][9][10]. There are a number of active stimuli that have been employed, such as change in temperature [9,11,12], magnetic field [10], pH [12,13], light [14], ultrasound [15] and radio-frequency [16] to trigger liposomes.…”