Tailoring the efficacy of nimodipine drug delivery using nanocarriers based on A2B miktoarm star polymers

Abstract

a b s t r a c tWe report a nanocarrier based on A 2 B type miktoarm polymers (A ¼ polyethylene glycol (PEG); B ¼ polycaprolactone (PCL)) for nimodipine (NIM), a hydrophobic drug with very poor aqueous solubility that is commonly prescribed for the prevention and treatment of delayed ischemic neurological disorders. The A 2 B star polymers were constructed on a core with orthogonal functionalities that facilitated the performance of "click" chemistry followed by ring-opening polymerization. These star polymers assemble into spherical micelles into which NIM can be easily loaded by the co-solvent evaporation method. The micelles obtained from the star polymer PEG775 2 ePCL5800 showed NIM encapsulation efficiency of up to 78 wt% at a feed weight ratio of 5.0%. The loading efficiency of the micelles was dependent on the length of the PCL arm in the A 2 B miktoarm polymers. Aqueous solubility of NIM was increased by w200 fold via micellar encapsulation. The in vitro release of NIM from the micelles was found to occur at a much slower rate than from its solution. Lipopolysaccharide induced nitric oxide production in N9 microglia cells was reduced in the presence of micelle-encapsulated NIM, as well as in the presence of micelles alone. The treatment of microglia with micelle-encapsulated NIM reduced the release of TNF-a, a pro-inflammatory cytokine. These results suggest that NIM-loaded miktoarm micelles could be useful in the treatment of neuroinflammation.

Design and Evaluation of Multifunctional Nanocarriers for Selective Delivery of Coenzyme Q10 to Mitochondria

“…35 Empty and CoQ10-loaded miktoarm micelles were prepared in deionized water by the cosolvent evaporation method which is simple and easy to scale up. 17 To optimize the size of the micelles, colloidal stability, and CoQ10 loading capacity, a series of ABC miktoarm polymers were prepared in which the chain length of the PEG arm was kept constant at 2 kDa, whereas that of the PCL arm was varied from 3.5 to 7.8 kDa (Table 1).…”

“…Longer PCL chains usually lead to the formation of bigger micelles due to their incorporation in the core of the micelles. 17,36 CoQ10 Incorporation into PEG2-PCL-TPPBr Miktoarm Polymer Micelles. CoQ10-loaded PEG2-PCL-TPPBr miktoarm polymer micelles were prepared by a cosolvent evaporation method.…”

“…42−44 Moreover, we have recently found that the maximum loading capacity of nimodipine, a hydrophobic calcium channel blocker into PCL-based linear and miktoarm polymers was about 3−5 wt % and was not affected by polymer architecture. 17 The extent of drug loading into a given polymeric micelle formulation is dependent on many factors, the most important of which is the compatibility between the drug and the polymer. Several recent studies have shown that polymer−drug compatibility is a key factor in determining the performance of polymeric micelle as drug delivery systems where high compatibility results in higher drug solubility, loading capacity, and controlled drug release.…”

Mesoporous drug carrier systems for enhanced delivery rate of poorly water-soluble drug: nimodipine

“…According to the biopharmaceutics classification system (BCS) it belongs to group II [5], and its bioavailability after oral administration is just 15.9 % on average [6]. Thus, conventional therapy with NM in the form of tablets or capsules requires administration of frequently taken much higher doses [7]. For these reasons, the use of a carrier that would improve the solubility of NM in body fluids and enhance drug delivery, seems much promising.…”

Multivalent niacin nanoconjugates for delivery to cytoplasmic lipid droplets

“…Miktoarm carrier containing two PEG 750 chains and a benzylic alcohol group [33]. BODIPY-Azide, Linear unit containing long chain alcohol and an acetylenic arm, and the dendrimer containing the long chain alcohol arms and free acetylenic groups [31].…”