Zeta potential changing nanoemulsions: Impact of PEG-corona on phosphate cleavage

Alkaline Phosphatase: A Reliable Endogenous Partner for Drug Delivery and Diagnostics

“…Phosphatidic acid (1,2-dipalmitoyl-sn-glycero-3-phosphatidic acid, PA) has been exploited as ALP-responsive excipient for the design of charge reversal lipid-based NCs. [212,213] Phospholipids exhibiting a choline substructure cannot be properly cleaved by ALP, as the phosphate substructure is a nonterminal diester. In order to address this issue, inversephosphocholine lipids were designed by Perttu et al [214] These inverse phospholipids exhibiting a terminal phosphate group were synthesized using trialkylphosphites as phosphorylating reagents.…”

“…[218] PEGylated emulsifiers form a PEG corona on the surface of SEDDS or nanoemulsions hindering the enzyme on phosphate cleavage. This corona effect was shown by Zaichik et al, as in the absence of PEGylated emulsifiers zeta potential changes of Δ40 mV upon contact with ALP were measured whereas nanoemulsions containing polyethoxylated-35 castor oil remained constant without any significant change in zeta potential due to the hindrance of PA. [213] Furthermore, a significant amount of phosphate was released from DOCP liposomes upon incubation with ALP due to absence of such a PEG corona on the surface. [214] In order to overcome PEG-corona, phosphorylated surfactants with PEG spacer arms were utilized and Δ21.6 mV and Δ41.9 mV changes in zeta potential were achieved for POAP [218] and PNPP [104] containing formulations, respectively.…”

“…Unlike FP-2PT-Chems loaded liposomes, control liposomes containing a sulfonated lipo-peptide (FP-2Sul-Chems) were not uptaken by B16F10 cells showing that uptake took place upon removal of phosphate moieties by ALP. Similarly, surface of polyl-lysine bearing nanoemulsions was covered by polyphosphates through electrostatic interactions to generate charge reversal Acyl substitution through covalent amide bond Stearic acid phosphotyrosine amide 3.6-fold -Synthesized excipient is a promising tool for developing zeta potential changing system [ 225] Phosphorylation of polymers using phosphorous pentoxides Starch phosphate and hydroxypropyl starch phosphate 2.5-fold and 5.4-fold -Strategy for enhancing bioavailability of drugs administered through mucosal route [ 193] Effect of water movement on mucus permeation Desmopressin loaded oily droplets 5-fold -Mucus permeation of NCs is independent from drug release [ 250] Nanoemulsions Zwitterions used as auxiliary agent Phosphorylated tyramine 8.59-fold 2.4-fold Alternative to cationic surfactants [ 223] Impact of PEG-corona on zeta potential changing nanoemulsions PEG free nanoemulsions 2-fold -Enhanced zeta potential changing behavior of nanoemulsions to improve mucosal drug delivery [ 213] Phosphorylated surfactant exhibiting PEG spacer Polyoxyethylene (9) nonylphenol monophosphate ester (PNPP) -…”

Development and In Vitro Characterization of Transferrin-Decorated Nanoemulsion Utilizing Hydrophobic Ion Pairing for Targeted Cellular Uptake

“…The surfactants CTAB and PA were added in order to stabilize the emulsion and to serve as counter ion for pairing with Tf. Phospholipid PA is widely used as emulsion stabilizer and is responsible for a highly negative surface charge and long-term stability under test conditions as described previously [23,24]. Tf was attached on the droplet surface via HIP providing a protein corona.…”

Preparation and Evaluation of Charge Reversal Solid Lipid Nanoparticles

“…In comparison to nanoemulsions reversing the zeta potential from -20 mV to +20 mV [23], nanoparticles are far away from their full potential. As proposed by our research group, surfactants comprising a spacer between the lipophilic moiety and the phosphate group are favorable as they overcome the PEG corona of nanoemulsions, which can provide a steric hindrance for IAP [17,24,25]. In parallel, phosphorylated surfactants in SLN need to remain accessible for IAP to reverse their surface charge.…”