Poloxamer 407

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Poloxamer 407 (P407) is a hydrophilic non-ionic surfactant. It is a triblock copolymer, which is composed of a central hydrophobic block of polypropylene glycol and two hydrophilic blocks of polyethylene glycol (PEG).

Skeleton formula of poloxameres, where P407 has block lengths of a=101 and b=56.Fig.1 Skeleton formula of poloxameres, where P407 has block lengths of a=101 and b=56.

P407/TPGS Mixed Micelles as Promising Carriers for Cyclosporine Ocular Delivery

This method aimed to develop a water micelle formulation using a water-soluble derivative of vitamin E (TPGS: D-α-germinol polyethylene glycol 1000 succinate) and P407 as excipients for efficient delivery of cyclosporine to eye tissue. Firstly, cyclosporine solubility was studied, and the appropriate proportion and concentration of P407: TPGS were selected to determine the preparation method of cyclosporine-loaded formulations. Then the particle size, zeta potential, morphology, rheology, and stability after dilution and freeze-drying of formulations were characterized. Cyclosporine-loaded micelles exhibited proper characteristics for ocular administration, sufficient stability against dilution, and adequate rheological properties at 35oC, and they can be sterilized by filtration and then freeze-dried without the need for a cryoprotectant. After dilution in simulated tears, cyclosporine-loaded mixed micelles effectively retained the drug and were stable during freeze-drying in the presence of 20 mm surfactant concentration. Drug-loaded mixed micelles were applied to porcine cornea in vitro and compared with ikervis. The drug accumulation in the cornea is directly proportional to the drug concentration. Finally, it is worth mentioning that the mixed micelles described can represent a useful platform for the ocular delivery of other lipophilic drugs. This could be very interesting, considering the good results obtained in scleral accumulation and trans-scleral delivery and the growing interest in the noninvasive targeting of the retina.

P407/TPGS mixed micelles as promising carriers for cyclosporine ocular delivery.Fig.2 P407/TPGS mixed micelles as promising carriers for cyclosporine ocular delivery. (Grimaudo, 2018)

Thermosensitive Micelles-Hydrogel Hybrid System Based on P407 for Localized Delivery of Paclitaxel

Different amounts of glutaraldehyde (GA) were applied to generate cross-linked networks with carboxymethyl chitosan (CMCS) interpenetrated in P407 gels, in which paclitaxel (PTX)-loaded N-octyl-O-sulfate chitosan micelles (PTX-M) were dispersed uniformly. The CMCS-modified P407 gels (PTX-M-MG) were obtained. The incorporation of CMCS-GA cross-linked networks finally transformed the thermosensitive P407 gels into non-thermosensitive hydrogels with higher swell ratios, stronger mechanical properties, and improved drug-release profile. The parameters suggested that P407-CMCS/GA hydrogels containing 0.05% (w/v) GA could be a remarkable drug carrier for in situ injection. The PTX-M-MG with 0.05% (w/v) GA has lower viscosity, higher swelling rate, stronger mechanical properties, and a longer drug release period. The introduction of PTX-M improves the drug loading efficiency of PTX. It can be seen that PTX-M-MG is a promising local delivery system of hydrophobic drugs, which can improve the curative effect and alleviate the side effects.

A schematic representation of the thermosensitive micelles-hydrogel hybrid system based on P407.Fig.3 A schematic representation of the thermosensitive micelles-hydrogel hybrid system based on P407. (Ju, 2013)

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References

  1. Grimaudo, M.A.; et al. Poloxamer 407/TPGS mixed micelles as promising carriers for cyclosporine ocular delivery. Molecular pharmaceutics. 2018, 15(2): 571-584.
  2. Ju, C.; et al. Thermosensitive micelles-hydrogel hybrid system based on poloxamer 407 for localized delivery of paclitaxel. Journal of pharmaceutical sciences. 2013, 102(8): 2707-2717.
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