pH dependent conformational changes in the T-and R-states of insulin in solution: Circular dichroic studies in the pH range of 6 to 10

Kim, Yesook; Shields, James E.

doi:10.1016/0006-291x(92)90862-f

Cited by 10 publications

(5 citation statements)

References 8 publications

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“…The CD spectra showed insulin, IPC-DNVs, 8%-L-T, and 8%-T have two minima at 208 and 223 nm, which is a typical α-helix structure. This is in close agreement with the spectra obtained by others [33,34]. However, the CD spectra of 8%-L were smooth and had no minima at 208 and 222 nm.…”

Section: Resultssupporting

confidence: 92%

Stabilization of Deformable Nanovesicles Based on Insulin-Phospholipid Complex by Freeze-Drying

Guo

Yang

et al. 2019

Pharmaceutics

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Deformable nanovesicles have been extensively investigated due to their excellent ability to penetrate biological barriers. However, suffering from serious physical and chemical instabilities, the wide use of deformable nanovesicles in medical applications is still limited. Moreover, far less work has been done to pursue the lyophilization of deformable nanovesicles. Here, we aimed to obtain stable deformable nanovesicles via freeze-drying technology and to uncover the underlying protection mechanisms. Firstly, the density of nanovesicles before freeze-drying, the effect of different kinds of cryoprotectants, and the types of different reconstituted solvents after lyophilization were investigated in detail to obtain stable deformable nanovesicles based on insulin-phospholipid complex (IPC-DNVs). To further investigate the underlying protection mechanisms, we performed a variety of analyses. We found that deformable nanovesicles at a low density containing 8% lactose and trehalose in a ratio of 1:4 (8%-L-T) have a spherical shape, smooth surface morphology in the lyophilized state, a whorl-like structure, high entrapment efficiency, and deformability after reconstitution. Importantly, the integrity of IPC, as well as the secondary structure of insulin, were well protected. Accelerated stability studies demonstrated that 8%-L-T remained highly stable during storage for 6 months at 25 °C. Based on in vivo results, lyophilized IPC-DNVs retained their bioactivity and had good efficacy. Given the convenience of preparation and long term stability, the use of combined cryoprotectants in a proper ratio to protect stable nanovesicles indicates strong potential for industrial production.

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Section: Resultssupporting

confidence: 92%

Stabilization of Deformable Nanovesicles Based on Insulin-Phospholipid Complex by Freeze-Drying

Guo

Yang

et al. 2019

Pharmaceutics

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“…Also tests with pseudoscalar mesons, albeit interesting, look far from a suitable way for eliminating detection loophole[15] 2. Incidentally, it must be noticed that the perfect fitting of SQM predictions to data obtained by varying one polarizer angle for various different settings of the other one both obtained in our experiments as in many other ones[1,18] conclusively falsifies LHVT based on the violation of rotational invariance, e.g [19]…”

supporting

confidence: 59%

Experimental tests of hidden variable theories from dBB to stochastic electrodynamics

Genovese

Brida

Gramegna

et al. 2007

J. Phys.: Conf. Ser.

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The studies concerning the possible existence of a deterministic theory, of which quantum mechanics would be an approximation, date to the celebrated 1935 Einstein-Podolsky-Rosen paper. Since Bells proposal of 1964 various experiments were addressed to a general experimental test of local hidden variable theories, leading to strong indications favourable to Standard Quantum Mechanics. Nevertheless, detection loophole still persists. In this, after a short presentation of recent PDC photon experiments, we will present our recent works in this field and in particular a conclusive negative test of stochastic electrodynamics. Finally, we will also mention possible tests of non-local deterministic models and give some detail on our test of the dBB model.

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“…This was in close agreement with the spectra obtained by others. 22,23 All of the released insulin had a CD spectrum very similar to the CD spectrum of free insulin. Furthermore, the α-helix ratio was between 23.3% and 28.4%, which was in agreement with that of free insulin (23.5%).…”

Section: Structural Analysis Of Nanovesiclesmentioning

confidence: 82%

Mechanisms of deformable nanovesicles based on insulin-phospholipid complex for enhancing buccal delivery of insulin

Xu¹,

Zhang²,

Zhang³

et al. 2018

IJN

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BackgroundNon-injectable delivery of peptides and proteins are not feasible due to its large molecular, high hydrophilic and gastrointestinal degradation. Therefore, proposing a new method to solve this problem is a burning issue.PurposeThe objective of this study was to propose a novel protein delivery strategy to vanquish the poor efficacy of buccal mucosa delivery systems for protein delivery and then investigate the detailed mechanisms of the enhanced buccal delivery of protein, using insulin as a model drug.Materials and methodsInsulin-phospholipid complex combined with deformable nanovesicles (IPC-DNVs) were prepared, using deformable nanovesicles based on insulin (INS-DNVs) and conventional nanovesicles based on insulin-phospholipid complex (IPC-NVs) as references. Besides, their physicochemical characterization, in vitro transport behavior, in vivo bioactivity and hypoglycemic effect were systematically characterized and compared. Finally, we evaluated the in vivo safety of IPC-DNVs.ResultsFirst, IPC-DNVs increased insulin permeability through deposition of the IPC and deformability of the DNVs, which was revealed by an in vitro mucosal permeation study. Second, DNVs could act as a drug carrier and penetrate the mucosa to reach the receiver medium as intact nanovesicles, which was supported by the observation of intact nanovesicles in the receiver medium through transmission electron microscopy (TEM). Third, IPC-DNVs exhibited both transcellular and paracellular transport in the form of IPC and DNVs, respectively, which was proved by confocal laser scanning microscopy (CLSM). Unlike the other two formulations, IPC-DNVs exhibited a sustained mild hypoglycemic effect, with a relative bioavailability (Fp) of 15.53% (3.09% and 1.96% for INS-DNVs and IPC-NVs, respectively). Furthermore, buccal administration of IPC-DNVs resulted in no visible mucosal irritation to the buccal mucosa.ConclusionOur work reveals the mechanisms underlying the enhanced buccal delivery of IPC-DNVs: the DNVs facilitate penetration through the main barrier, and the deposition of IPC enhances buccal absorption. Our results and proposed mechanisms could be an important reference to understand other nanocarriers based on protein (peptide)-phospholipid complexes that penetrate the mucosa and provide a theoretical basis for the future development of buccal delivery systems for insulin.

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pH dependent conformational changes in the T-and R-states of insulin in solution: Circular dichroic studies in the pH range of 6 to 10

Cited by 10 publications

References 8 publications

Stabilization of Deformable Nanovesicles Based on Insulin-Phospholipid Complex by Freeze-Drying

Stabilization of Deformable Nanovesicles Based on Insulin-Phospholipid Complex by Freeze-Drying

Experimental tests of hidden variable theories from dBB to stochastic electrodynamics

Mechanisms of deformable nanovesicles based on insulin-phospholipid complex for enhancing buccal delivery of insulin

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