Nanostructured Lipid Carriers for Oral Bioavailability Enhancement of Exemestane: Formulation Design, In Vitro, Ex Vivo, and In Vivo Studies

Singh, Archu; Neupane, Yub Raj; Mangla, Bharti; Kohli, Kanchan

doi:10.1016/j.xphs.2019.06.003

Cited by 94 publications

(46 citation statements)

References 68 publications

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“…It has been reported that non-ionic surfactants (e.g., polysorbate 80 or polysorbate 20) in the presence of lyoprotectant can preserve the biological activity of protein-based therapeutics [ 41 ] and can also provide steric stabilization to nanoparticles [ 42 , 43 ]. Therefore, in this study, the non-reducing disaccharides sucrose or trehalose were added in combination with polysorbate 80.…”

Section: Resultsmentioning

confidence: 99%

Lyophilization Preserves the Intrinsic Cardioprotective Activity of Bioinspired Cell-Derived Nanovesicles

et al. 2021

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Recently, bioinspired cell-derived nanovesicles (CDNs) have gained much interest in the field of nanomedicine due to the preservation of biomolecular structure characteristics derived from their parent cells, which impart CDNs with unique properties in terms of binding and uptake by target cells and intrinsic biological activities. Although the production of CDNs can be easily and reproducibly achieved with any kind of cell culture, application of CDNs for therapeutic purposes has been greatly hampered by their physical and chemical instability during long-term storage in aqueous dispersion. In the present study, we conceived a lyophilization approach that would preserve critical characteristics regarding stability (vesicles’ size and protein content), structural integrity, and biological activity of CDNs for enabling long-term storage in freeze-dried form. Compared to the lyoprotectant sucrose, trehalose-lyoprotected CDNs showed significantly higher glass transition temperature and lower residual moisture content. As assessed by ATR-FTIR and far-UV circular dichroism, lyophilization in the presence of the lyoprotectant effectively maintained the secondary structure of cellular proteins. After reconstitution, lyoprotected CDNs were efficiently associated with HeLa cells, CT26 cells, and bone marrow-derived macrophages at a rate comparable to the freshly prepared CDNs. In vivo, both lyoprotected and freshly prepared CDNs, for the first time ever reported, targeted the injured heart, and exerted intrinsic cardioprotective effects within 24 h, attributable to the antioxidant capacity of CDNs in a myocardial ischemia/reperfusion injury animal model. Taken together, these results pave the way for further development of CDNs as cell-based therapeutics stabilized by lyophilization that enabled long-term storage while preserving their activity.

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Section: Resultsmentioning

confidence: 99%

Lyophilization Preserves the Intrinsic Cardioprotective Activity of Bioinspired Cell-Derived Nanovesicles

et al. 2021

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“…The concentration of the stabilizer has a significant antagonistic impact on the particle size of the developed NLCs (Figures 2 and 3, Table 3), as a higher amount of stabilizer would readily emulsify the total lipids incorporated in the preparation, resulting in the conversion of the large-sized lipid particles into smaller ones. On the contrary, the insufficient amount of a stabilizer in lipid nanocarriers contributes to the instability and re-agglomeration of the particles [39].…”

Section: Effect Of Stabilizer Concentration On Particle Sizementioning

confidence: 99%

Nanostructured Lipid Carriers to Mediate Brain Delivery of Temazepam: Design and In Vivo Study

et al. 2020

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The opposing effect of the blood–brain barrier against the delivery of most drugs warrants the need for an efficient brain targeted drug delivery system for the successful management of neurological disorders. Temazepam-loaded nanostructured lipid carriers (NLCs) have shown possibilities for enhancing bioavailability and brain targeting affinity after oral administration. This study aimed to investigate these properties for insomnia treatment. Temazepam-NLCs were prepared by the solvent injection method and optimized using a 42 full factorial design. The optimum formulation (NLC-1) consisted of; Compritol® 888 ATO (75 mg), oleic acid (25 mg), and Poloxamer® 407 (0.3 g), with an entrapment efficiency of 75.2 ± 0.1%. The average size, zeta potential, and polydispersity index were determined to be 306.6 ± 49.6 nm, −10.2 ± 0.3 mV, and 0.09 ± 0.10, respectively. Moreover, an in vitro release study showed that the optimized temazepam NLC-1 formulation had a sustained release profile. Scintigraphy images showed evident improvement in brain uptake for the oral 99mTc-temazepam NLC-1 formulation versus the 99mTc-temazepam suspension. Pharmacokinetic data revealed a significant increase in the relative bioavailability of 99mTc-temazepam NLC-1 formulation (292.7%), compared to that of oral 99mTc-temazepam suspension. Besides, the NLC formulation exhibited a distinct targeting affinity to rat brain. In conclusion, our results indicate that the developed temazepam NLC formulation can be considered as a potential nanocarrier for brain-mediated drug delivery in the out-patient management of insomnia.

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“…As well, Liu et al [42] and Zhu et al [71] reported that the PEG‐40 stearate could competitively inhibit the activity of P‐gp efflux pumps by saturating the P‐gp receptors as a substrate and decrease its efflux activity in the P‐gp ATPase activity study. Moreover, it was reported that the lipid‐based nanocarriers formulated by using various digestive lipids such as phospholipids, glycosides, cholesterol esters and fatty acids enhance the intestinal permeability of the drug by increasing its transport from intestine, and the presence of surfactants decrease the intestinal efflux by blocking the P‐gp efflux pump located in the enterocytes of the GIT [72, 73].…”

Section: Resultsmentioning

confidence: 99%

Development of tamoxifen‐loaded surface‐modified nanostructured lipid carrier using experimental design: in vitro and ex vivo characterisation

Ganesan

Damodharan

2020

IET nanobiotechnol.

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The present study aimed to develop a surface-modified biocompatible nanostructured lipid carrier (NLCs) system using polyoxyethylene (40) stearate (POE-40-S) to improve the oral bioavailability of poorly water-soluble Biopharmaceutics Classification System class-II drug like tamoxifen (TMX). Also aimed to screen the most influential factors affecting the particle size (PS) using Taguchi (L 12 (2 11)) orthogonal array design (TgL 12 OA). Then, to optimize the TMX loaded POE-40-S (P) surface-modified NLCs (TMX-loaded-PEG-40-S coated NLC (PNLCs) or PNLCs) by central composite design (CCD) using a four-factor, five-level model. The most influential factors affecting the PS was screened and optimized. The in-vitro study showed that increased drug-loading (DL) and encapsulation efficiency (EE), decreased PS and charge, sustained drug release for the prolonged period of the time with good stability and suppressed protein adsorption. The Ex-vivo study showed that decreased mucous binding with five-fold enhanced permeability of PNLC formulation after surface modification with POE-40-S. The in-vitro cytotoxicity study showed that the blank carrier is biocompatible and cytotoxicity of the formulation was dependent on the concentration of the drug. Finally, it can be concluded that the surface-modified PNLCs formulation was an effective, biocompatible, stable formulation in the enhancement of dissolution rate, solubility, stability with reduced mucus adhesion and increased permeability thereby which indicates its enhanced oral bioavailability.

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Nanostructured Lipid Carriers for Oral Bioavailability Enhancement of Exemestane: Formulation Design, In Vitro, Ex Vivo, and In Vivo Studies

Cited by 94 publications

References 68 publications

Lyophilization Preserves the Intrinsic Cardioprotective Activity of Bioinspired Cell-Derived Nanovesicles

Lyophilization Preserves the Intrinsic Cardioprotective Activity of Bioinspired Cell-Derived Nanovesicles

Nanostructured Lipid Carriers to Mediate Brain Delivery of Temazepam: Design and In Vivo Study

Development of tamoxifen‐loaded surface‐modified nanostructured lipid carrier using experimental design: in vitro and ex vivo characterisation

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