TABLE 1.
Lipid-based nanocarriers for E2 delivery: route of administration, composition, physical -chemical characteristics, manufacturing process, in vitro/in vivo performance.
| Type of nanoparticle | Route of administration | Composition | Particle size (nm) | PDI | ZP (mV) | EE/DL (% mm) | Preparation methods | In vivo and/or in vitro performance | References |
|---|---|---|---|---|---|---|---|---|---|
| LED | Transdermic | 1,1 Di ((Z) - octadec-9-en-1-yl) piperidin-1-ium iodide | 167.4 | 0.51 | 22.7 ± 6 | 74.3 | modified ethanol injection method | LED - E2 permeated deeper and delivered to the dermal layer | Marepally S 2013 |
| LP | - | DOPC DOPC: DDAB DOPC:DMPG |
217 ± 6 199 ± 6 207 ± 2 |
0.124 ± 0.038 0.136 ± 0.006 0.113 ± 0.002 |
−0.46 ± 2.93 +26.72 ± 4.06 −28.00 ± 4.61 |
41.7 ± 4.2 51.2 ± 3.6 42.8 ± 2.9 |
thin-film hydration technique | DOPC liposomes with cationic DDAB had the highest E2 loading capacity and better cellular uptake | Bowey K 2014 |
| LP | Subcutaneous | Main lipid (DPPC, DMPC or POPC), DDAB, cholesterol and E2 (molar ratio 1/0.2/0.6/0.2, total lipid concentration: 25 μM); HEPES buffer 10 mM (pH 7.4); PE-PEG2000 (2 mol%) | 138 ± 4 | 0.06 ± 0.02 | +27 ± 3 | 3.0 ± 0.9 | thin-film hydration technique | E2 in LP can be a useful tool to indicate molecular mechanisms related to ERα | Gallez A 2020 |
| NE | - | Flaxseed oil (w-3 polyunsaturated fatty acid a- linoleic acid), Lipoid® E80 (2.4%, w/v), DSPE-PEG2000 (0.3%, w/v), deionized water, DOTAP (0.3%, w/v), chloroform, ethanol | 138 ± 9 | 0.14 | −33.80 ± 2.45 | 92.6 ± 4.6 | microfluidization technique | E2 NE inhibited vascular smooth muscle cells (VSMC) and supported endothelial cells in connection with MAPK signaling | Deshpande D 2013 |
| NE | Buccal Transmucosal | Transcutol P™, PEG 400, Tween 80, and deionized water | 14.92 | 0.487 | - | 97.50 | ultrasonication | A successful formulation was prepared, and it could be a promising administration route for E2 delivery | Abdella A 2022 |
Abbreviations: LED, Lipid - Ethanol - Drug Nanoparticle; LP, Liposome; NE, Nanoemulsion; LP, liposome; PDI, polydispersity index; ZP, zeta potential; EE, Encapsulation efficacy; DL, drug loading; DMPC, dimyristoyl phosphatidyl choline; DMPG, dimyristoyl phosphatidyl glycerol; DPPC, dipalmitoyl phosphatidyl choline; DOPE, dioleoyl phosphatidyl ethanolamine; DDAB, dimethyldioctadecylammonium; DSPC, 1,2-distearoyl-sn-glycero-3-phosphocholine; mPEG DSPE, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000; SPC, soybean phosphatidylcholine; mPEG2000-DSPE, methylpolyethyleneglycol-1, 2-distearyl-phosphatidylethanolamine conjugate; DMAP, p-dimethylamino pyridine; PRL, pH-responsive lipid derivative; HSPC, hydrogenated soybean phosphatidylcholine; DMPG-Na, 1,2-Dimyristoyl-sn-glycero-3-phosphoglycerol sodium salt; DSPG-Na, Distearoyl-sn-glycero-3- phosphoglycerol sodium salt; SA-3 M, 2,4,6-trimethoxybenzilidene-pentaerythritol coupled with Stearic acid; CTM-Ag, Clotrimazole-silver complex; PEG-660 stearate/Solutol HS15, 12-hydroxystearic acid-polyethylene glycol copolymer. 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine- N- [maleimide (polyethylene glycol)-2000] (ammonium salt) (DSPE-PEG (2000) Maleimide), DPPC (palmitic acid; 16 atoms of carbon) and DMPC (myristic acid; 14 atoms of carbon) were selected as saturated lipids. 1-palmitoyl-2-oleoylsn- glycero-3-phosphocholine (POPC); (flaxseed oil) rich in the ω-3 polyunsaturated fatty acid (PUFA) α-linolenic acid; 1,2-dioleolyl-3-trimethylammonium-propane (DOTAP).