The in vivo transformation and pharmacokinetic properties of a liquid crystalline drug delivery system

Otte, Andrew; Báez-Santos, Yahira M.; Mun, Ellina A.; Soh, Bong-Kwan; Lee, Youngnam; Park, Kinam

doi:10.1016/j.ijpharm.2017.08.098

Cited by 15 publications

(5 citation statements)

References 24 publications

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“…The current understanding is that, these nanostructured nonlamellar LLC phases are developed to overcome the suboptimal performance of the commonly used micelle, emulsion, and liposome systems in terms of local and systemic tolerability, encapsulation efficiency, physical instability, manufacturing and excipient costs, and more importantly, sustained‐release control . Interestingly, Otte et al recently revealed the in vivo transformation of a H 2 phase precursor depot formulation injected subcutaneously to a rat model, and showed that an earlier LC phase transformation (day 1 vs day 3) in conjunction with reduced matrix viscosity is associated with higher drug release and hence, increased bioavailability parameters . How the kinetics of LC formation in the body affects tissue tolerability has yet to be clarified.…”

Section: In Vivo and Clinical Safety Aspects Of Llc Materialsmentioning

confidence: 99%

Self‐Assembled Nanostructured Lipid Systems: Is There a Link between Structure and Cytotoxicity?

Tan

Hong

et al. 2018

Advanced Science

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Self‐assembly of lipid‐based liquid crystalline (LLC) nanoparticles is a formulation art arising from the hydrophilic–lipophilic qualities and the geometric packing of amphiphilic lipid molecules in an aqueous environment. The diversity of commercialized amphiphilic lipids and an increased understanding of the physicochemical factors dictating their membrane curvature has enabled versatile architectural design and engineering of LLC nanoparticles. While these exotic nanostructured materials are hypothesized to form the next generation of smart therapeutics for a broad field of biomedical applications, biological knowledge particularly on the systemic biocompatibility or cytotoxicity of LLC materials remains unclear. Here, an overview on the interactions between LLCs of different internal nanostructures and biological components (including soluble plasma constituents, blood cells, and isolated tissue cell lines) is provided. Factors affecting cell–nanoparticle tolerability such as the type of lipids, type of steric stabilizers, nanoparticle surface charges, and internal nanostructures (or lipid phase behaviors) are elucidated. The mechanisms of cellular uptake and lipid transfer between neighboring membrane domains are also reviewed. A critical analysis of these studies sheds light on future strategies to transform LLC materials into a viable therapeutic entity ideal for internal applications.

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Section: In Vivo and Clinical Safety Aspects Of Llc Materialsmentioning

confidence: 99%

Self‐Assembled Nanostructured Lipid Systems: Is There a Link between Structure and Cytotoxicity?

Tan

Hong

et al. 2018

Advanced Science

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“…B. subtilis has PE as the main lipid component of its membrane. The phospholipid, PE, is thought to play a significant role in membrane-membrane fusion [48] by inducing negative membrane curvature [49], which helps in the attainment of the stalk-like state that may act as an early intermediate during the process of fusion [50,51]. During the union, PE interacts with surrounding water molecules less firmly in a more energetically favorable condition due to its peculiar shape and charge.…”

Section: Discussionmentioning

confidence: 99%

“…During the union, PE interacts with surrounding water molecules less firmly in a more energetically favorable condition due to its peculiar shape and charge. Hence, it circumvents the repulsive hydration forces ensuing in the fusion of the approaching bilayers [50]. Further, the PE phospholipid in the inverted hexagonal (HII) phase enables the formation of membrane defects in the bilayer, thereby bringing the bilayers of two fusing vesicles into close proximity [52].…”

Section: Discussionmentioning

confidence: 99%

Potential of siRNA-Bearing Subtilosomes in the Treatment of Diethylnitrosamine-Induced Hepatocellular Carcinoma

et al. 2023

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Therapeutics, based on small interfering RNA (siRNA), have demonstrated tremendous potential for treating cancer. However, issues such as non-specific targeting, premature degradation, and the intrinsic toxicity of the siRNA, have to be solved before they are ready for use in translational medicines. To address these challenges, nanotechnology-based tools might help to shield siRNA and ensure its specific delivery to the target site. Besides playing a crucial role in prostaglandin synthesis, the cyclo-oxygenase-2 (COX-2) enzyme has been reported to mediate carcinogenesis in various types of cancer, including hepatocellular carcinoma (HCC). We encapsulated COX-2-specific siRNA in Bacillus subtilis membrane lipid-based liposomes (subtilosomes) and evaluated their potential in the treatment of diethylnitrosamine (DEN)-induced hepatocellular carcinoma. Our findings suggested that the subtilosome-based formulation was stable, releasing COX-2 siRNA in a sustained manner, and has the potential to abruptly release encapsulated material at acidic pH. The fusogenic property of subtilosomes was revealed by FRET, fluorescence dequenching, content-mixing assay, etc. The subtilosome-based siRNA formulation was successful in inhibiting TNF-α expression in the experimental animals. The apoptosis study indicated that the subtilosomized siRNA inhibits DEN-induced carcinogenesis more effectively than free siRNA. The as-developed formulation also suppressed COX-2 expression, which in turn up-regulated the expression of wild-type p53 and Bax on one hand and down-regulated Bcl-2 expression on the other. The survival data established the increased efficacy of subtilosome-encapsulated COX-2 siRNA against hepatocellular carcinoma.

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“…Both of the in-situ-forming gel formulations that consisted of glycerol dioleate (GDO)–phosphatidylcholine (PC) and PC in combination with sorbitol monooleate (PC:SMO), Tween grade 80, and tocopherol acetate (TA) were optimized and compared with Risperdal CONSTA ® (Janssen Pharmaceuticals, NJ, USA). On the other hand, rat models have been employed for the pharmacokinetic evaluation of (i) 5-fluorouracil-loaded Pluronic F127-MO cubosomes that have additionally shown targeted accumulation in liver tissues [ 90 ], (ii) a leuprolide-acetate-loaded hexagonal LC matrix composed of PC, SMO, and tocopherol acetate (TA) [ 91 ], (iii) a PC:SMO LC system for the subcutaneous delivery of naltrexone [ 92 ], and (iv) technetium-99 m (99mTc)-radiolabeled phytantriol and oleic acid-based hexosomes [ 75 ]. Interestingly, the utilization of single-photon emission computed tomography (SPECT) in combination with CT was described for monitoring the in vivo biodistribution of the 99mTc-radiolabeled hexosomes.…”

Section: Pharmacokinetic Modulation Using Lcnpsmentioning

confidence: 99%

Recent Advances in the Development of Liquid Crystalline Nanoparticles as Drug Delivery Systems

Leu,

Teoh,

Ling

et al. 2023

Pharmaceutics

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Due to their distinctive structural features, lyotropic nonlamellar liquid crystalline nanoparticles (LCNPs), such as cubosomes and hexosomes, are considered effective drug delivery systems. Cubosomes have a lipid bilayer that makes a membrane lattice with two water channels that are intertwined. Hexosomes are inverse hexagonal phases made of an infinite number of hexagonal lattices that are tightly connected with water channels. These nanostructures are often stabilized by surfactants. The structure’s membrane has a much larger surface area than that of other lipid nanoparticles, which makes it possible to load therapeutic molecules. In addition, the composition of mesophases can be modified by pore diameters, thus influencing drug release. Much research has been conducted in recent years to improve their preparation and characterization, as well as to control drug release and improve the efficacy of loaded bioactive chemicals. This article reviews current advances in LCNP technology that permit their application, as well as design ideas for revolutionary biomedical applications. Furthermore, we have provided a summary of the application of LCNPs based on the administration routes, including the pharmacokinetic modulation property.

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The in vivo transformation and pharmacokinetic properties of a liquid crystalline drug delivery system

Cited by 15 publications

References 24 publications

Self‐Assembled Nanostructured Lipid Systems: Is There a Link between Structure and Cytotoxicity?

Self‐Assembled Nanostructured Lipid Systems: Is There a Link between Structure and Cytotoxicity?

Potential of siRNA-Bearing Subtilosomes in the Treatment of Diethylnitrosamine-Induced Hepatocellular Carcinoma

Recent Advances in the Development of Liquid Crystalline Nanoparticles as Drug Delivery Systems

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