Recent Advances in Oral Peptide or Protein-Based Drug Liposomes
Abstract
:1. Introduction
2. Properties of Protein and Peptide Drugs
3. Phospholipid Materials Suitable for the Oral Administration of Liposomes
4. Preparation Methods for Polypeptide Liposomes
5. Stability Strategy
5.1. Alteration of Liposome Membrane Composition
5.2. Embedded Bile Salts
5.3. Surface-Coating Strategy
5.4. Diversified Dosage Forms
API | Phospholipid | Strategy to Protect Liposomes from the Damage of GIT | Properties | EE (%) ± SD | MD (nm) ± SD | Zeta (mv) ± SD | Ref |
---|---|---|---|---|---|---|---|
Myrcludex B | EPC | GCTE, which is resistant to hydrolysis and oxidation, was embedded in the phospholipid bilayer | At least 7% of the initial dose of Myrcludex B was absorbed, with a 3.5-fold increase in oral effectiveness | 65.7 ± 2.9 | 140.7 ± 4.3 | −4.2 ± 0.5 | [25] |
rhINS | SPC DPPG Chol | Phytosterols with stronger interactions with phospholipids were used instead of cholesterol | After 4 h in SGF, Er-lip retained more than 70% of the insulin; the plasma glucose level could be reduced to about 60% of the initial value and kept low for 8 h | 30 ± 2.0 | 157.1 ± 0.4 | −60.5 ± 9.8 | [41] |
rhINS | SPC | GCA was able to reduce the degradation of liposomes in GIT and promote the internalization of lipid particles | High oral bioavailability of 11.0%, with a mild and lasting hypoglycemic effect | 35 ± 2.1 | 358 ± 28.0 | - | [42] |
Calcitonin | PC DSPG Chol | Surface-modified CPPs and TMC promoted the cellular uptake of liposomes | Effectively enhanced the oral absorption of calcitonin | 80 ± 2.0 | 118 ± 18.0 | −27.1 ± 5.8 | [47] |
FID | DPPC DPPE-MCC | Chitosan coating with thiol group modification enhanced the adhesion and permeability of liposomes and inhibited the degradation of lipid membranes by enzymes | Papp was 2.8–3.4 times stronger than the initial value | - | 702.6 ± 138.0 | 8.62 ± 1.4 | [44] |
Insulin | DPPC | Silica coating isolated liposomes from digestive enzymes | Silica coating was able to reduce the lipolysis rate and continuously release the drug for up to 8 h | 70.0 | 297 ± 0.4 | −15 ± 4.0 | [45] |
Bee venom | PC | Liposomes were encapsulated into Eudragit S100-coated calcium alginate gel microspheres to slow the drug leakage of liposomes at non-specific sites | Liposomes completed drug release at the colon and maintained structural integrity in Git | 95.36 ± 0.3 | 2.05 ± 0.7 mm | - | [46] |
rhINS | E-PC | Liposomes with chitosan coating were encapsulated into double extrusion by “two-step” microfluidic technology | Exhibited the characteristics of pH-responsive release and accelerated the intracellular internalization of encapsulated insulin | 91 ± 4.0% | 19 ± 1.0 μm | - | [11] |
6. Receptor-Mediated Transportation across Enterocytes
7. Small Intestine-Lymphatic Circulation Prevents the First-Pass Effect
8. Inhibition of P-gp and CYP3A4
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Agent | Phospholipid | Formulation | Property | Modification | EE (%) ± SD | Zeta (mv) ± SD | MD (nm) ± SD | Gain | Ref |
---|---|---|---|---|---|---|---|---|---|
Insulin | DMPG (PSC) | Stirring ultrasonic | Anionic phospholipid | - | 70.9 ± 2.0 | 6.2 ± 0.5 | 29.8 ± 2.3 | Degradation of insulin was reduced | [6] |
Salmon calcitonin | DPPC DPPE-MCC | TFH + FTC | Amphoteric phospholipid | CS–TGA and CS–TGA–MNA modification | 69 ± 12.0 | 27.9 ± 1.1 | 604.8 ± 29.6 | Reduces blood calcium by 35% | [7] |
BSA | SPC | Supercritical assisted process | Amphoteric phospholipid | - | 95 ± 3.0 | 25 ± 5.0 | 250 ± 58.0 | Up to 90% encapsulation rate | [8] |
Silymarin (SM) | SPC | Supercritical assisted process | Amphoteric phospholipid | SGC modification | 91.4 | −62.3 | 160.50 | SM-Lip-SEDS Cmax, AUC increases | [9] |
HGH | EPC (GCTE) | DAC | Amphoteric phospholipid | GCTE | 31.2 ± 0.5 | 41.0 ± 1.2 | 229.7 ± 12.8 | 3.4% oral bioavailability | [10] |
RhIns | PC, DSPE-PEG, Chol | MHF | Amphoteric phospholipid | Chitosan coated with double emulsion carrier | 91 ± 4 | 23 ± 1.0 | 363 ± 54 | The stability and permeability of rhIns increase | [11] |
BSA | SPC | RPE | Cationic phospholipid | chitosan coated | 44.2 ± 0.3 | 33.1 ± 0.6 | 173.7 ± 5.6 | More stable | [12] |
Calcitonin | DSPC DCP Chol | TFH | Amphoteric phospholipid | Protease inhibitor modified chitosan | >75 | 39.9 ± 1.6 | 4460.0 | Increases the AAC | [13] |
Exendin-4 | DOPC DOTAP | RPE | Anionic phospholipid | GCA modified chitosan coating | 74.2 ± 2.5 | −31 ± 0.2 | 229 ± 4.0 | 19% oral bioavailability | [14] |
Insulin | SPC | RPE | Amphoteric phospholipid | Biotin-DSPE promotes absorption | - | 38.5 ± 3.5 | 150.0 | 12% oral bioavailability | [15] |
Insulin | SPC | RPE | Amphoteric phospholipid | Thiamine and nicotinic acid Decoration | 30.6 ± 2.4 | - | 125.6 ± 2.9 | 2.5% oral bioavailability | [16] |
Insulin | EPC: Chol DOTAP | TFH | Cationic phospholipid | Protein adsorption | 28.7 ± 5.1 | −23.1 ± 0.5 | 164.7 ± 5.3 | 12% oral bioavailability | [17] |
Cy5-amine | POPC POPS, | TFH | Anionic phospholipid | Alginate microcapsule | - | −12.0± 1.0 | 124 ± 13.0 | Longer residence time in the intestine | [18] |
Salmon calcitonin | PC | TFH | Amphoteric phospholipid | Bile salt modification | 54.9 ± 4.1 | - | 741 ± 76.9 | 7.1-times higher bioavailability of sCT | [19] |
Insulin | SPC Chol | TFH | Amphoteric phospholipid | FcBP receptor modification | 70.9 ± 2.0 | 6.2 ± 0.5 | 29.8 ± 2.3 | Blood sugar decreased by 47.87% | [20] |
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Cui, J.; Wen, Z.; Zhang, W.; Wu, W. Recent Advances in Oral Peptide or Protein-Based Drug Liposomes. Pharmaceuticals 2022, 15, 1072. https://doi.org/10.3390/ph15091072
Cui J, Wen Z, Zhang W, Wu W. Recent Advances in Oral Peptide or Protein-Based Drug Liposomes. Pharmaceuticals. 2022; 15(9):1072. https://doi.org/10.3390/ph15091072
Chicago/Turabian StyleCui, Jian, Zhiwei Wen, Wei Zhang, and Wei Wu. 2022. "Recent Advances in Oral Peptide or Protein-Based Drug Liposomes" Pharmaceuticals 15, no. 9: 1072. https://doi.org/10.3390/ph15091072