Comparative studies on glycerol monooleate- and phytantriol-based cubosomes containing oridonin <i>in vitro</i> and <i>in vivo</i>

Sildenafil citrate (SIL), a type 5-specific phosphodiesterase inhibitor, demonstrates valuable results in the management of infertility in women; however, the absence of vaginal dosage form in addition to the associated oral adverse effects minimize its clinical performance. The present study is concerned with SIL uterine targeting following intravaginal administration via optimization of cubosomal in situ gelling sponges (CIS). An emulsification method was employed for preparation of cubosomal dispersions incorporating glyceryl monooleate as a lipid phase and poloxamer 407 as a surfactant with or without polyvinyl alcohol as a stabilizer. Cubosomes were estimated regarding entrapment efficiency (EE%), particle size, and in vitro drug release. Chitosan (2% w/w) was incorporated into the optimum formulation and then lyophilized into small sponges. For the CIS, in vivo histopathological and pharmacokinetic studies were conducted on female Wistar rats and compared with intravaginal free SIL sponges (FIS) and oral SIL solution. SIL-loaded cubosomes showed EE% ranging between 32.15 and 72.01%, particle size in the range of 150.81–446.02 nm and sustained drug release over 8 h. Histopathological study revealed a significant enlargement in endometrial thickness with congestion and dilatation of endometrial blood vessels in intravaginal CIS compared to intravaginal FIS and oral-treated groups. The pharmacokinetic study demonstrated higher AUC0–∞ and Cmax with oral administration compared to intravaginal CIS or intravaginal FIS indicating potential involvement of first uterine pass effect after intravaginal administration. Finally, intravaginal CIS could be considered as a promising platform for SIL uterine targeting with minimized systemic exposure and side effects.

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“…A similar finding of oridonin release from GMO- and phytantriol-based cubosomes was reported by Shi et al. ( 2017 ).…”

Section: Methodssupporting

confidence: 89%

Novel in situ gelling vaginal sponges of sildenafil citrate-based cubosomes for uterine targeting

et al. 2018

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“…In a paper concerning comparative in vitro and in vivo studies on glycerol monooleate and phytantriol-based cubosomes containing oridonin [206], the zero- and first-order models, as well as Higuchi and Weibull equations, were tested. A linear relationship was established between the release rate and the square root of time for both cubosome formulations, indicating that the release kinetics fit Higuchi’s equation and were controlled by drug diffusion.…”

Section: Release Models Based On Fick’s First Lawmentioning

confidence: 99%

Mathematical Modeling of Release Kinetics from Supramolecular Drug Delivery Systems

et al. 2019

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Embedding of active substances in supramolecular systems has as the main goal to ensure the controlled release of the active ingredients. Whatever the final architecture or entrapment mechanism, modeling of release is challenging due to the moving boundary conditions and complex initial conditions. Despite huge diversity of formulations, diffusion phenomena are involved in practically all release processes. The approach in this paper starts, therefore, from mathematical methods for solving the diffusion equation in initial and boundary conditions, which are further connected with phenomenological conditions, simplified and idealized in order to lead to problems which can be analytically solved. Consequently, the release models are classified starting from the geometry of diffusion domain, initial conditions, and conditions on frontiers. Taking into account that practically all solutions of the models use the separation of variables method and integral transformation method, two specific applications of these methods are included. This paper suggests that “good modeling practice” of release kinetics consists essentially of identifying the most appropriate mathematical conditions corresponding to implied physicochemical phenomena. However, in most of the cases, models can be written but analytical solutions for these models cannot be obtained. Consequently, empiric models remain the first choice, and they receive an important place in the review.

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“…Although various emulsifiers have been investigated for preparing novel lipid-based dispersion systems from the cubic liquid crystal [16,17], the most widely used system is the ternary system of Glycerol monooleate (GMO) and P407-water, in which P407 is commonly applied in stabilizing the dispersion of Cubs, while the unique structure of GMO makes Cubs able to be embedded, controlling the release of drugs with different molecular weights and polarities [18–20]. …”

Section: Introductionmentioning

confidence: 99%

Folic Acid-Targeted Etoposide Cubosomes for Theranostic Application of Cancer Cell Imaging and Therapy

Tian

Zhu

et al. 2017

Med Sci Monit

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BackgroundThe aim of this study was to develop a novel Poloxamer-based drug delivery system featuring a tumor-targeting folate moiety, which was expected to provide better targeting properties and therapeutic effects compared with the traditional cubosomes (Cubs).Material/MethodsBoth folate-modified Cubs containing etoposide (ETP-Cubs-FA) and normal cubic nanoparticles loaded with etoposide (ETP-Cubs) were prepared through the fragmentation of bulk gels under the homogenization condition of 1500 bar, and a mean particle size of around 180 nm was obtained with a narrow size distribution. The cubosomes were further characterized by differential scanning calorimetry (DSC) and Polarized light microscopy (PLM). The release of ETP in vitro from these nanoparticles was found to be 82.5% at 36 h, showing a sustained release property compared with the free drug administration.ResultsFolate-modified cubosomes exhibited best anti-proliferative activity followed by normal cubosomes and the free drug. A further cell uptake study of Rhodamine B-loaded Cubs-FA (Rh-B-Cubs-FA) showed a marked increase of cellular accumulation compared with free Rh-B and Rh-B-loaded Cubs (Rh-B-Cubs). In vivo Rh-B-based tumor imaging demonstrated that Cubs-FA specifically targeted the tumor tissue.ConclusionsThe folate-modified cubosomes containing ETP may be a promising drug candidate for antitumor treatment.

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Comparative studies on glycerol monooleate- and phytantriol-based cubosomes containing oridonin in vitro and in vivo

Cited by 33 publications

References 26 publications

Novel in situ gelling vaginal sponges of sildenafil citrate-based cubosomes for uterine targeting

Novel in situ gelling vaginal sponges of sildenafil citrate-based cubosomes for uterine targeting

Mathematical Modeling of Release Kinetics from Supramolecular Drug Delivery Systems

Folic Acid-Targeted Etoposide Cubosomes for Theranostic Application of Cancer Cell Imaging and Therapy

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