Drug-in-hydroxypropyl-ß-cyclodextrin-in-lipoid S100/cholesterol liposomes: Effect of the characteristics of essential oil components on their encapsulation and release.

Drug-in-cyclodextrin-in-liposome (DCL) represents a very promising approach for preserving essential oil (EO) components, thereby extending their shelf life and activity. In this study, we examined the effect of chemical structure, octanol/water partition coefficient (log P), and Henry's law constant (Hc) on the encapsulation and the release of monoterpenes (eucalyptol, pulegone, terpineol, and thymol) and phenylpropenes (estragole and isoeugenol) from DCLs. Hydroxypropyl-ß-cyclodextrin/EO component (HP-ß-CD/EO component) inclusion complexes were prepared in aqueous solution and loaded into liposomes by the ethanol injection method. The phospholipid:cholesterol:EO component molar ratio determined for DCL structures was affected by characteristics of EO components. The presence of a propenyl tail or a hydroxyl group in the structure of EO component may improve its loading into DCLs. Furthermore, low encapsulation efficiency (EE) was obtained for DCLs exhibiting high cholesterol membrane content. In addition, a positive linear relationship was found between the loading ratio of monoterpenes into DCLs and their hydrophobic character expressed as log P. The release of components from DCLs was influenced by their EE into the formulations. Finally, DCL formulations retain considerable amounts of EO components after 10 months.

New findings on the incorporation of essential oil components into liposomes composed of lipoid S100 and cholesterol.

The encapsulation of essential oil components into liposomes was demonstrated to improve their solubility and chemical stability. In this study, we investigated the effect of chemical structure, Henry's law constant (Hc), and aqueous solubility of essential oil components on their liposomal encapsulation. Estragole, eucalyptol, isoeugenol, pulegone, terpineol, and thymol were encapsulated in lipoid S100-liposomes using the ethanol injection method. The Hc values were determined. The incorporation in liposomes was more efficient (encapsulation efficiency > 90%) for the essential oil components exhibiting low aqueous solubility (estragole, isoeugenol, and pulegone). Moreover, efficient entrapment into vesicles (loading rate > 18%) was obtained for isoeugenol, terpineol, and thymol. This result suggests that the presence of a hydroxyl group in the structure and a low Hc value enhance the entrapment of essential oil components into liposomes. Furthermore, drug release rate from liposomes was controlled by the loading rate of essential oil components into liposomes, the size of particles, the location of essential oil components within the lipid bilayer, and the cholesterol incorporation rate of liposomes. Finally, considerable concentrations of isoeugenol, pulegone, terpineol, and thymol were retained in liposomes after 10 months with respect to the initial concentration.

Post-harvest management control of Ectomyelois ceratoniae (Zeller) (Lepidoptera: Pyralidae): new insights through essential oil encapsulation in cyclodextrin.

BACKGROUND: Essential oils are reported to be bio-insecticides. However, problems related to their volatility, oxidation and poor water solubility need to be solved before they can be considered as replacement pest control methods. Thus, an appropriate formulation is needed for commercial use. In this work, a new control method based on the use of a powdered cyclodextrin (CD)/1,8-cineole inclusion complex was assessed against larvae and adults of Ectomyelois ceratoniae (Zeller) in comparison with two Rosmarinus officinalis (L.) essential oils, free 1,8-cineole (oils major compound) and a mixture of 50% CD/1,8-cineole inclusion complex and 50% free 1,8-cineole. RESULTS: Solid CD/1,8-cineole complex was more toxic against E. ceratoniae larvae than the two crude essential oils. At a concentration of 15 µL liter-1 air, the respective mortalities were 94.12%, 35.29% and 19.61% for solid CD/1,8-cineole complex, Thala and Cap Zbib oils after 37 days of exposure. Moreover, the solid CD/1,8-cineole complex achieved 5% adult emergence versus 68.33% for Cap Zbib and 55% for Thala oils. The half-life of solid CD/1,8-cineole inclusion complex (10.98 days) was considerably longer than that of the mixture (7.53 days) or free 1,8-cineole (3.43 days). CONCLUSION: This work highlights the utility of essential oil encapsulation in CD to overcome restrictions when used to control the date moth E. ceratoniae during storage. © 2019 Society of Chemical Industry.

Hydroxypropyl-ß-cyclodextrin as a membrane protectant during freeze-drying of hydrogenated and non-hydrogenated liposomes and molecule-in-cyclodextrin-in- liposomes: Application to trans-anethole.

The effect of hydrogenation of phospholipids on the characteristics of freeze-dried liposomes was investigated using hydroxypropyl-ß-cyclodextrin (HP-ß-CD) as membrane protectant. The ethanol-injection method was applied to prepare liposomes using hydrogenated (Phospholopion-90H and 80H) and non-hydrogenated phospholipids (Lipoid-S100) in combination with cholesterol. Various liposomal formulations were tested: conventional liposomes (CL) and HP-ß-CD-loaded liposomes (CDL). Liposome suspensions were concentrated by ultracentrifugation; the pellets were reconstituted in water or CD solution and the dispersions were characterized for their size, polydispersity index and zeta potential. Results demonstrated that HP-ß-CD protected only the hydrogenated batches (CL and CDL) during freeze-drying. Moreover, the presence of HP-ß-CD in the aqueous phase of CDL protected them during freeze-drying. Freeze-dried CL and CDL made of phospholipon-90H loading anethole were demonstrated to be physically stable upon reconstitution in HP-ß-CD solutions, and are able to retain anethole after 6 months of storage at 4 °C thereby making them valuable for food applications.

Interaction of Selected Phenylpropenes with Dipalmitoylphosphatidylcholine Membrane and Their Relevance to Antibacterial Activity.

The effect of structurally closely related phenylpropenes (PPs), estragole, anethole, eugenol, and isoeugenol, on the fluidity of dipalmitoyl phosphatidyl choline (DPPC) liposome membrane was investigated by DSC, Raman, and fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH). Liposomes were prepared by thin-film hydration method at various DPPC:PP molar ratios. The DPH anisotropy measurements of blank and PP-loaded liposomes were performed at 28, 41, and 50 °C, which correspond, respectively, to gel phase, main transition temperature of DPPC, and liquid phase. The Raman images showed the formation of nano- and micrometric spherical multi-lamellar vesicles. All studied PPs exhibited a membrane fluidizing effect which was reinforced by the presence of phenolic hydroxyl group in eugenol and isoeugenol. The PPs interacted with the choline head group and the alkyl chains of DPPC membrane, wherein isoeugenol and anethole possessing the same C7-C8 position of the double bond in the propenyl side chain, incorporated deeply in the bilayer. Additionally, the PPs were analyzed for antibacterial activity against E. coli by macrobroth dilution method. Anethole and estragole were more efficient in inhibiting the bacterial growth than eugenol and isoeugenol. We conclude that the fluidizing effect of PPs on the membrane is a common mechanism that is not related to the hydrophobicity of the PP molecule. Besides, other target sites may be involved in PP antibacterial activity against Gram-negative bacteria. The greater hydrophobicity of these PPs may contribute to their penetrability through the outer bacterial membrane.

Drug-in-cyclodextrin-in-liposomes as a carrier system for volatile essential oil components: Application to anethole.

A combined approach based on cyclodextrin/drug inclusion complex formation and loading into liposomes was applied to improve the effectiveness of liposome loading with essential oils. Hydroxypropyl-ß-cyclodextrin/ANE (HP-ß-CD/ANE) inclusion complexes were prepared and encapsulated into liposomes (ACL). ANE-double-loaded liposomes (ACL2) were obtained with the HP-ß-CD/ANE complex in the aqueous phase and ANE in the organic phase. Liposomes were prepared from saturated (Phospholipon 90H) or unsaturated (Lipoid S100) phospholipids and characterized for size, polydispersity index, zeta potential, morphology, loading rate (LR) and photo- and storage stabilities. All liposome batches were nanometric oligolamellar-type vesicles. Compared to ANE-loaded liposomes, ACL-90H, ACL2-90H and ACL2-S100 displayed significantly increased ANE LR, with ACL2-S100 exhibiting the highest LR. All formulations provided ANE photoprotection, were physically stable after 15months of storage at 4°C (with the exception of ACL2-S100), and retained more than 25% of the ANE initially present in the liposome suspensions.

Preparation of drug-in-cyclodextrin-in-liposomes at a large scale using a membrane contactor: Application to trans-anethole.

The present study aimed to prepare liposomes loaded with cyclodextrin/drug inclusion complexes at a pilot scale based on the ethanol injection technique. Anethole (ANE), a major component of anise and fennel essential oils, was used as a model of a volatile and highly hydrophobic drug. Membrane contactor (600mL) and a pilot plant (3L) were used for liposome production. The liposome preparations obtained were characterized for size, polydispersity index, zeta potential, morphology, stability and ANE release rate. All experimental set-ups were shown to be appropriate for the preparation of small, multilamellar vesicles with narrow size distribution and good stability at 4°C. The drug release study showed that only a small amount of ANE was released from liposome formulations after 21days of storage at 4°C. The loading rate of ANE was higher when ethanol was evaporated directly on the pilot plant compared to a rotary evaporation.

Liposomes incorporating cyclodextrin-drug inclusion complexes: Current state of knowledge.

Cyclodextrins (CDs) are cyclic oligosaccharides, consisting of glucopyranose units, which are able to form host-guest inclusion complexes with lipophilic molecules. The ability of CD to increase drug solubility may be used to increase drug entrapment in the aqueous compartment of liposomes and liposomes can protect CD/drug inclusion complexes until drug release. Liposomes are phospholipid vesicles composed of lipid bilayers enclosing one or more aqueous compartments. They have been widely used as safe and effective carriers for both hydrophilic and lipophilic drugs. However, lipophilic drugs incorporated in the membrane bilayers can be rapidly released, which limits the effectiveness of this drug delivery system. The coupling of both delivery systems by encapsulating CD/drug inclusion complex into liposomes is proposed to circumvent the drawbacks of each separate system. Here, we review the literature regarding the encapsulation of CD/drug inclusion complex into conventional, deformable and double loaded liposomes. The review highlights the characteristics of these systems and presents the advantages and disadvantages of each one.