Self-nanoemulsifying drug delivery systems (SNEDDS) and self-microemulsifying drug delivery systems (SMEDDS) as lipid nanocarriers for improving dissolution rate and bioavailability of poorly soluble drugs

Krstić, Marko; Medarević, Djordje; Đuriš, Jelena; Ibrić, Svetlana

doi:10.1016/b978-0-12-813687-4.00012-8

Cited by 55 publications

(53 citation statements)

References 96 publications

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“…There are established mature SMEDDS products on the market [ 25 ], such as cyclosporine A SMEDDS Neoral ® (Novartis, Basel, Switzerland) [ 26 ]. The CAT3-SMEDDS developed in this study disperses easily in water, and the droplet size is about 30 nm.…”

Section: Discussionmentioning

confidence: 99%

Improved Safety and Anti-Glioblastoma Efficacy of CAT3-Encapsulated SMEDDS through Metabolism Modification

Wang

et al. 2021

Molecules

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13a-(S)-3-pivaloyloxyl-6,7-dimethoxyphenanthro(9,10-b)-indolizidine (CAT3) is a novel oral anti-glioma pro-drug with a potent anti-tumor effect against temozolomide-resistant glioma. 13a(S)-3-hydroxyl-6,7-dimethoxyphenanthro(9,10-b)-indolizidine (PF403) is the active in vivo lipase degradation metabolite of CAT3. Both CAT3 and PF403 can penetrate the blood–brain barrier to cause an anti-glioma effect. However, PF403, which is produced in the gastrointestinal tract and plasma, causes significant gastrointestinal side effects, limiting the clinical application of CAT3. The objective of this paper was to propose a metabolism modification for CAT3 using a self-microemulsifying drug delivery system (SMEDDS), in order to reduce the generation of PF403 in the gastrointestinal tract and plasma, as well as increase the bioavailability of CAT3 in vivo and the amount of anti-tumor substances in the brain. Thus, a CAT3-loaded self-microemulsifying drug delivery system (CAT3-SMEDDS) was prepared, and its physicochemical characterization was systematically carried out. Next, the pharmacokinetic parameters of CAT3 and its metabolite in the rats’ plasma and brain were measured. Furthermore, the in vivo anti-glioma effects and safety of CAT3-SMEDDS were evaluated. Finally, Caco-2 cell uptake, MDCK monolayer cellular transfer, and the intestinal lymphatic transport mechanisms of SMEDDS were investigated in vitro and in vivo. Results show that CAT3-SMEDDS was able to form nanoemulsion droplets in artificial gastrointestinal fluid within 1 min, displaying an ideal particle size (15–30 nm), positive charge (5–9 mV), and controlled release behavior. CAT3-SMEDDS increased the membrane permeability of CAT3 by 3.9-fold and promoted intestinal lymphatic transport. Hence, the bioavailability of CAT3 was increased 79% and the level of its metabolite, PF403, was decreased to 49%. Moreover, the concentrations of CAT3 and PF403 were increased 2–6-fold and 1.3–7.2-fold, respectively, in the brain. Therefore, the anti-glioma effect in the orthotopic models was improved with CAT3-SMEDDS compared with CAT3 in 21 days. Additionally, CAT3-SMEDDS reduced the gastrointestinal side effects of CAT3, such as severe diarrhea, necrosis, and edema, and observed less inflammatory cell infiltration in the gastrointestinal tract, compared with the bare CAT3. Our work reveals that, through the metabolism modification effect, SMEDDS can improve the bioavailability of CAT3 and reduce the generation of PF403 in the gastrointestinal tract and plasma. Therefore, it has the potential to increase the anti-glioma effect and reduce the gastrointestinal side effects of CAT3 simultaneously.

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Section: Discussionmentioning

confidence: 99%

Improved Safety and Anti-Glioblastoma Efficacy of CAT3-Encapsulated SMEDDS through Metabolism Modification

Wang

et al. 2021

Molecules

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“…The architecture of the skin presented in Figure 2, is based on three types of layer with a specific cellular composition that promotes protection: the epidermis, dermis, and hypodermis [43,44]. microemulsion in biological fluids for oral delivery [32]. In topical therapy of dermatologic conditions, an increased solubility and bioavailability was obtained for molecules like: cyclosporine in psoriasis [33]; ceramides for skin restructuration [34]; imiquimod in actinic keratosis or basal cell carcinoma [35]; penciclovir [36], acyclovir for herpes virus simplex cutaneous infection [37]; and tenoxicam for arthritis alleviation [38].…”

Section: Skin Structure and Implications In Topical Delivery Of Activmentioning

confidence: 99%

Foray into Concepts of Design and Evaluation of Microemulsions as a Modern Approach for Topical Applications in Acne Pathology

et al. 2020

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With a fascinating complexity, governed by multiple physiological processes, the skin is considered a mantle with protective functions which during lifetime are frequently impaired, triggering dermatologic disorders. As one of the most prevalent dermatologic conditions worldwide, characterized by a complex pathogenesis and a high recurrence, acne can affect the patient’s quality of life. Smart topical vehicles represent a good option in the treatment of a versatile skin condition. By surpassing the stratum corneum known for diffusional resistance, a superior topical bioavailability can be obtained at the affected place. In this direction, the literature study presents microemulsions as a part of a condensed group of modern formulations. Microemulsions are appreciated for their superior profile in matters of drug delivery, especially for challenging substances with hydrophilic or lipophilic structures. Formulated as transparent and thermodynamically stable systems, using simplified methods of preparation, microemulsions have a simple and clear appearance. Their unique structures can be explained as a function of the formulation parameters which were found to be the mainstay of a targeted therapy.

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“…Zeta potential is the measurement of the electrostatic potential of nanoparticles' surface and it is a good indicator for nanoparticles' stability. [57,58] HT-ZnO NPs have a zeta potential of −8.23 ± 0.26 mV ( Figure A.4, Appendix A. Supplementary Data), suggesting moderate stability.…”

Section: Dynamic Light Scattering (Dls)mentioning

confidence: 99%

Green synthesis of zinc oxide nanoflowers using Hypericum triquetrifolium extract: characterization, antibacterial activity and cytotoxicity against lung cancer A549 cells

Sharie

El‐Elimat

Darweesh

et al. 2020

Applied Organom Chemis

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Zinc oxide nanoparticles have attracted significant interest in recent years due to their unique multifunctional chemical and physical properties along with their biological activities. This study demonstrated for the first time the biogenetic synthesis of zinc oxide nanoparticles by utilization of the methanolic extract of Hypericum triquetrifolium (HT). The obtained nanoparticles (HT-ZnO) were characterized by ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM). The shape of the resulted nanoparticles is fusiform nanoflowers with an average hydrodynamic size of 275.46 ± 0.20 nm and a zeta potential of −8.23 ± 0.26 mV. SEM micrographs revealed that HT-ZnO nanoflowers have a multi-process structure in which one of the processes is large and the others have similar smaller dimensions. The synthesized nanoflowers have an average length of 312.28 ± 78.93 nm and the tip of its processes has a width of 48.69 ± 9.71 nm. The antimicrobial activity of HT-ZnO nanoflowers was performed using microbroth dilution format. It showed a bactericidal mode of action against Gram-positive Staphylococcus aureus and Enterococcus faecalis with MIC/MBC values of 20 μg/mL and 5 μg/mL, respectively. MTT assay had revealed that HT-ZnO nanoflowers caused a dose-dependent decline in the viability of A549 adenocarcinomic human alveolar basal epithelial cells with an IC 50 value of 20.45 μg/mL. The effect of HT-ZnO nanoflowers on the migration and colony formation abilities against the same cells was evaluated as well. In conclusion, zinc oxide nanoflowers were successfully synthesized using methanolic extract of H. triquetrifolium. The resulting particles showed a bactericidal effect against Gram-positiveS. aureus and E. faecalis and a cytotoxic activity against A549 cells.

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Self-nanoemulsifying drug delivery systems (SNEDDS) and self-microemulsifying drug delivery systems (SMEDDS) as lipid nanocarriers for improving dissolution rate and bioavailability of poorly soluble drugs

Cited by 55 publications

References 96 publications

Improved Safety and Anti-Glioblastoma Efficacy of CAT3-Encapsulated SMEDDS through Metabolism Modification

Improved Safety and Anti-Glioblastoma Efficacy of CAT3-Encapsulated SMEDDS through Metabolism Modification

Foray into Concepts of Design and Evaluation of Microemulsions as a Modern Approach for Topical Applications in Acne Pathology

Green synthesis of zinc oxide nanoflowers using Hypericum triquetrifolium extract: characterization, antibacterial activity and cytotoxicity against lung cancer A549 cells

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