Assembly of amphiphilic poly[2‐(methacryloyloxy)ethyl phosphorylcholine] with cholesteryl moieties as terminal groups

Abstract

Poly[2-(methacryloyloxy)ethyl phosphorylcholine]s (PMPCs) with one pendant cholesteryl moiety at the polymer end (PMPC-Chol-I and PMPC-Chol-II) and two pendant cholesteryl moieties at both polymer ends as terminal groups (PMPC-2Chol-I and PMPC-2Chol-II) were prepared by the radical polymerization of 2-(methacryloyloxy)ethyl phosphorylcholine initiated with 4,4Ј-azobis[(3-cholesteryl)-4-cyanopentanoate] in the presence of 2-mercaptoethanol or thiocholesterol as chain-transfer reagents, respectively. The self-organization of PMPC-Chol and PMPC-2Chol was analyzed with fluorescence and 1 H NMR measurements. The critical micelle concentrations of PMPC-Chol-I with a degree of polymerization (P n ) of 91 and of PMPC-2Chol-I with a P n value of 165 were 250 and 27 mg L Ϫ1 , respectively. The blood compatibility of PMPC-2Chol was evaluated from the Michaelis constant (K m ) for the enzymatic reaction of thrombin and a synthetic substrate, S-2238, in the presence of PMPC-2Chol. K m was 0.07, 0.05, and 0.56 for PMPC-2Chol-I with P n ϭ 165, PMPC-2Chol-II with P n ϭ 38, and PMPC (an intrinsic viscosity of 0.54 dL g Ϫ1 ) initiated with 2,2Ј-azobisisobutyronnitrile in the absence of chain transfer agent, respectively. A mixture of PMPC-2Chol-II and cholesterol as a drug model formed a lamellar type of complex with an interplanar spacing of d ϭ 35.2 Å.

Cholesteryl moiety terminated amphiphilic polymethacrylates containing nucleic acid bases for drug delivery

“…In a previous paper, 17 choline side groups did not show any change. The half-width of the proton signal of cholesteryl moiety gradually broadened with an increase in the D 2 O content, while the peak completely disappeared in a 50 v/ v% D 2 O.…”

“…It is well-known that in the case of the copolymer of NiPAAm the LCST increases with the introduction of hydrophilic comonomer, whereas it decreases with the introduction of hydrophobic ones. 31,32 Thermoresponsible polymers like PNiPAAm-co-PMEA-Chol are considered to be useful anticancer drug-carrier molecules for a drug-delivery system (DDS) 11,17 mentioned below.…”

“…17 The DDS model was then prepared from PMEA-2Chol and cholesterol as a substitute of a lipophilic drug, as mentioned in experimental parts. Figure 6 depicts the DSC traces for the DDS model (PMEA-2Chol and cholesterol system) and cholesterol.…”

“…2,19,20 Polyacrylic acid modified with an N,N-dioctadecyl amide group as a terminal group forms a stable liposome with dipalmitoyl phosphatidylcholine. 14 We have reported that poly [N-(2-hydroxypropyl)methacrylamide]s 16 and poly[2-(methacryloyloxy)-ethylphosphorylcholine]s 17 with a single pendant cholesteryl group at the polymer end and two cholesteryl groups at both polymer ends as terminal groups can self-organize in an aqueous solution and exhibit critical micelle concentration (CMC). Poly(N-isopropylacrylamide) (PNiPAAm) substituted with two pendant n-octadecyl groups at the chain end can form multimolecular micelles, which consist of a rigid core of octadecyl chain and a corona of solvated PNIPAAm chain.…”

“…2 Since hydrophobically modified poly[N-(2-hydroxypropyl)-methacrylate]s and poly[2-(methacryloyloxy)ethyl phosphorylcholine]s form heterogeneous structure composed of a rigid core of cholesteryl group and a solvated corona of hydrophilic segments, drugs with a hydrophobic character can be held in a hydrophobic layer formed by terminated cholesteryl groups. 16,17 On the other hand, considering the ability to form intermolecular complexes of deoxyribonucleic acid (DNA), polymers, which contain nucleic acid bases, e.g., adenine and thymine, are expected to combine uridine and adenosine type of drugs, respectively, by complementary interaction. 21,22 In addition to the complementary intermolecular complex of DNA, an anticancer drug, cis-dichlorodiammine platinum(II) [cis-Pt(NH 3 )2Cl 2 : CDDP], can bind specifically to DNA in adenine, guanine, cytosine, and their derivatives.…”