Encapsulation of an insulin-modified phosphatidylcholine complex in a self-nanoemulsifying drug delivery system (SNEDDS) for oral insulin delivery

Bravo-Alfaro, Diego A.; Muñoz-Correa, María O.F.; Santos-Luna, Dalia; Toro‐Vázquez, Jorge F.; Cano-Sarmiento, Cynthia; García-Varela, Rebeca; Garcı́a, Hugo S.

doi:10.1016/j.jddst.2020.101622

Cited by 14 publications

(7 citation statements)

References 44 publications

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“…In our work, the relative oral bioavailability of insulin formulated in PEG-coated nanoparticles was calculated to be close to 10%, 2.5-fold higher than for bare nanoparticles. This oral bioavailability is higher than other values previously published with PLGAchitosan composite nanocarriers (about 8%; [57]) or SNEDDS (about 1.8%; [58]); although, it is lower (about 2-times) when compared with other previous results obtained with liposomes decorated with PEG and folic acid (19.08%; [59]), folate-chitosan nanoparticles (17.04%; [60]), or zein/caseinate-based nanoparticles co-encapsulating insulin and cholic acid (20.5%; [61]). In spite of the lower capability to promote the oral absorption of insulin, our formulation offers some interesting advantages that may facilitate a translational approach; particularly in those aspects related to the scale-up of a reproducible process (including the drying step) and the simplification of non-clinical toxicity assessments of the regulatory dossier.…”

Section: Discussioncontrasting

confidence: 57%

Zein-Based Nanoparticles as Oral Carriers for Insulin Delivery

et al. 2021

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Zein, the major storage protein from corn, has a GRAS (Generally Regarded as Safe) status and may be easily transformed into nanoparticles, offering significant payloads for protein materials without affecting their stability. In this work, the capability of bare zein nanoparticles (mucoadhesive) and nanoparticles coated with poly(ethylene glycol) (mucus-permeating) was evaluated as oral carriers of insulin (I-NP and I-NP-PEG, respectively). Both nanocarriers displayed sizes of around 270 nm, insulin payloads close to 80 µg/mg and did not induce cytotoxic effects in Caco-2 and HT29-MTX cell lines. In Caenorhabditis elegans, where insulin decreases fat storage, I-NP-PEG induced a higher reduction in the fat content than I-NP and slightly lower than the control (Orlistat). In diabetic rats, nanoparticles induced a potent hypoglycemic effect and achieved an oral bioavailability of 4.2% for I-NP and 10.2% for I-NP-PEG. This superior effect observed for I-NP-PEG would be related to their capability to diffuse through the mucus layer and reach the surface of enterocytes (where insulin would be released), whereas the mucoadhesive I-NP would remain trapped in the mucus, far away from the absorptive epithelium. In summary, PEG-coated zein nanoparticles may be an interesting device for the effective delivery of proteins through the oral route.

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Section: Discussioncontrasting

confidence: 57%

Zein-Based Nanoparticles as Oral Carriers for Insulin Delivery

et al. 2021

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“…Based on the results of the apigenin nanoemulsion globule size test on 10 formulas, it was found that the globule size ranged from 17.48 to 20.34 nm as listed in table 3 (with the normal globule size distribution curve) listed in Figure 1, the nanoemulsion globule size requirements were <100 nm 30 . Oil and surfactants produce a stable system that supports a decrease in globule size when in the form of nanoemulsions 31 . The use of surfactants and co-surfactants in nanoemulsion formulation technology can reduce surface tension causing a decrease in Gibbs free energy, thereby causing a decrease in particle size 32 .…”

Section: Evaluation Of Apigenin Nanoemulsion Characterizationmentioning

confidence: 99%

Formulation And Characterization Of Buccal Film Nanoemulsion Apigenin As Antidiabetic

Firmansya¹,

Setiawan²,

Nurdianti

et al. 2022

IJPST

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Apigenin (4`,5,7-trihydroxyflavone) is a flavonoid of subclass flavones that have antidiabetic therapeutic activity but limitations BCS Class II low solubility of 2.16 μg/L. To overcome these limitations, the development of nanoemulsion formulation technology, increasing solubility increases dissolution, absorption and bioavailability. It is incorporated into the buccal film for easy application and direct access to the systemic circulation. This study aims to obtain apigenin nanoemulsion with the best characterization and buccal film that meets the characterization. The method was carried out experimentally in the manufacture of nanoemulsions by spontaneous emulsification, a buccal film by solvent casting, and the characterization. 10 nanoemulsion formulas met the characterization with globule size <20.34nm, polydispersity index <0.131, zeta potential close to 0mV, pH 6.23-6.59, %transmittance close to 100% and best F10 incorporated into buccal film has 29x the solubility compared to apigenin with p≤0.05. All buccal films met the characterization with F3 having a 2x faster onset of release than F1&F2 with 86.07% diffusion and 97.9333 mg/sheet. Thus, it was concluded that the formulation and characterization of buccal film fulfilled the characterization and F10 apigenin nanoemulsion increased the solubility 29-fold with the buccal film F3 having a faster onset of release.

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“…Advanced SNEDDSs provide novel nano-emulsions with improved functional characteristics such as prolonged GI residence time, increased stability in GI fluids, improved mucus diffusion, improved permeation, and enhanced cell uptake, leading consequently to increased oral bio-availability of the encapsulated drugs [ 10 , 11 , 291 , 292 ]. Bravo-Alfaro et al [ 293 ] developed SNEDDSs containing an insulin complex along with modified or unmodified phosphatidylcholine to increase insulin oral bio-availability. Under i n vitro GI conditions, SNEDDSs showed 35.7% of drug availability upon reaching the final stage of the simulated small intestine.…”

Section: Advancements In Sneddssmentioning

confidence: 99%

Self-Nano-Emulsifying Drug-Delivery Systems: From the Development to the Current Applications and Challenges in Oral Drug Delivery

et al. 2020

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Approximately one third of newly discovered drug molecules show insufficient water solubility and therefore low oral bio-availability. Self-nano-emulsifying drug-delivery systems (SNEDDSs) are one of the emerging strategies developed to tackle the issues associated with their oral delivery. SNEDDSs are composed of an oil phase, surfactant, and cosurfactant or cosolvent. SNEDDSs characteristics, their ability to dissolve a drug, and in vivo considerations are determinant factors in the choice of SNEDDSs excipients. A SNEDDS formulation can be optimized through phase diagram approach or statistical design of experiments. The characterization of SNEDDSs includes multiple orthogonal methods required to fully control SNEDDS manufacture, stability, and biological fate. Encapsulating a drug in SNEDDSs can lead to increased solubilization, stability in the gastro-intestinal tract, and absorption, resulting in enhanced bio-availability. The transformation of liquid SNEDDSs into solid dosage forms has been shown to increase the stability and patient compliance. Supersaturated, mucus-permeating, and targeted SNEDDSs can be developed to increase efficacy and patient compliance. Self-emulsification approach has been successful in oral drug delivery. The present review gives an insight of SNEDDSs for the oral administration of both lipophilic and hydrophilic compounds from the experimental bench to marketed products.

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Encapsulation of an insulin-modified phosphatidylcholine complex in a self-nanoemulsifying drug delivery system (SNEDDS) for oral insulin delivery

Cited by 14 publications

References 44 publications

Zein-Based Nanoparticles as Oral Carriers for Insulin Delivery

Zein-Based Nanoparticles as Oral Carriers for Insulin Delivery

Formulation And Characterization Of Buccal Film Nanoemulsion Apigenin As Antidiabetic

Self-Nano-Emulsifying Drug-Delivery Systems: From the Development to the Current Applications and Challenges in Oral Drug Delivery

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