A New Approach for Preparing Stable High-Concentration Peptide Nanoparticle Formulations
Abstract
:1. Introduction
2. Results and Discussion
2.1. Peptide Nanomilling Approach
2.2. Insulin Nanosuspensions
2.3. GNE-A Nanosuspensions
2.4. Cyclosporine A Nanosuspension Formulations
2.5. Comparison with Alternative High-Energy Milling Approaches
3. Materials and Methods
3.1. Materials
3.2. Nanosuspension Screening Using Resonant Acoustic Milling
3.3. Nanosuspension Scale-Up
3.4. Analytical Characterization Methods
3.4.1. Particle Size Analysis Using Dynamic Light Scattering
3.4.2. Stability Analysis Using HPLC
3.4.3. Dry-State Transmission Electron Microscopy
3.4.4. Viscosity Measurements
3.4.5. Injection Force Measurements
3.5. Cyclosporine A In Vivo Pharmacokinetic Studies
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Peptide | Formulation (wt% to Insulin) | Average Radius (nm) | % Pd |
---|---|---|---|
Insulin Monomer | 25% HPC-SL, 1% SDS | 130 ± 4 | 28.3 |
25% PVP K29-32, 1% SDS | 112 ± 2 | 23.7 | |
25% Pluronic F127 | 419 ± 24 | 14.6 | |
25% Tween80 | 903 ± 124 | Multimodal |
Peptide | Formulation (wt% to Insulin) | Average Radius (nm) | % Pd |
---|---|---|---|
Insulin Monomer | 25% HPC-SL, 1% SDS | 135 ± 14 | 33.6 |
25% PVP K29-32, 1% SDS | 121 ± 5 | 19.9 |
Peptide | Formulation (wt% to GNE-A) | Average Radius (nm) | % Pd |
---|---|---|---|
GNE-A | 25% HPC-SL, 1% SDS | 142 ± 3 | 14 |
25% PVP K29-32, 1% SDS | 161 ± 37 | Multimodal | |
25% Pluronic F127 | 134 ± 5 | 16.4 | |
25% Tween 80 | 190 ± 8 | 21.4 |
Peptide | Formulation (wt% to GNE-A) | Average Radius (nm) | % Pd |
---|---|---|---|
GNE-A | 25% Pluronic F127 | 137 ± 4 | 27.3 |
25% Tween 80 | 104 ± 4 | 19.1 |
Peptide | Formulation (wt% to CsA) | Average Radius (nm) | % Pd |
---|---|---|---|
Cyclosporine A | 25% HPC-SL, 1% SDS | 307 ± 20 | 49.1 |
25% PVP K29-32, 1% SDS | 1177 ± 295 | Multimodal | |
25% Pluronic F127 | 480 ± 77 | Multimodal | |
25% Tween80 | 193 ± 7 | 21.8 |
Peptide | Formulation (wt% to CsA) | Average Radius (nm) | % Pd |
---|---|---|---|
Cyclosporine A | 25% HPC-SL, 1% SDS | 400 ± 32 | 31.9 |
25% Tween80 | 316 ± 14 | 26.9 |
Solubility (mg/mL) | 0% SDS | 10% SDS | 25% SDS | 50% SDS |
---|---|---|---|---|
Cyclosporine A | 0.038 | 1.047 | 3.848 | 8.599 |
Viscosity (Pa·s/CsA) | 5 mg/mL | 25 mg/mL | 50 mg/mL | 100 mg/mL |
---|---|---|---|---|
CsA Nanosuspension | 0.76 | 0.86 | n/a | 2.1 |
Sandimmune® CsA Solution | 2.1 | 297 | 92 | n/a |
Formulation | Dose (mg/kg) | AUClast (h*μmol/L) | Cmax (μmol/L) | Tmax (h) |
---|---|---|---|---|
Sadimmune® (CsA Solution) | 10 | 20.3 | 1.13 | 12 |
Sandimmune® (CsA Solution) | 50 | 59.2 | 3.38 | 24 |
Nanosuspension (CsA) | 10 | 3.04 | 0.149 | 24 |
Nanosuspension (CsA) | 50 | 7.49 | 0.409 | 11 |
Peptide Nanosuspension (wt% to Peptide) | Amp 20%/5 min | Amp 20%/10 min |
---|---|---|
CsA in 25% HPC-SL, 1% SDS | particle settled at bottom | particle settled at bottom |
GNE-A in 25% F127 | particle settled at bottom | particle settled at bottom |
Insulin in 25% PVP K29-32, 1% SDS | homogenous | homogenous |
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Hu, C.; Zang, N.; Tam, Y.T.; Dizon, D.; Lee, K.; Pang, J.; Torres, E.; Cui, Y.; Yen, C.-W.; Leung, D.H. A New Approach for Preparing Stable High-Concentration Peptide Nanoparticle Formulations. Pharmaceuticals 2024, 17, 15. https://doi.org/10.3390/ph17010015
Hu C, Zang N, Tam YT, Dizon D, Lee K, Pang J, Torres E, Cui Y, Yen C-W, Leung DH. A New Approach for Preparing Stable High-Concentration Peptide Nanoparticle Formulations. Pharmaceuticals. 2024; 17(1):15. https://doi.org/10.3390/ph17010015
Chicago/Turabian StyleHu, Chloe, Nanzhi Zang, Yu Tong Tam, Desmond Dizon, Kaylee Lee, Jodie Pang, Elizabeth Torres, Yusi Cui, Chun-Wan Yen, and Dennis H. Leung. 2024. "A New Approach for Preparing Stable High-Concentration Peptide Nanoparticle Formulations" Pharmaceuticals 17, no. 1: 15. https://doi.org/10.3390/ph17010015
APA StyleHu, C., Zang, N., Tam, Y. T., Dizon, D., Lee, K., Pang, J., Torres, E., Cui, Y., Yen, C. -W., & Leung, D. H. (2024). A New Approach for Preparing Stable High-Concentration Peptide Nanoparticle Formulations. Pharmaceuticals, 17(1), 15. https://doi.org/10.3390/ph17010015