Small Oligomeric Micelles Based on End Group Modified mPEG−Oligocaprolactone with Monodisperse Hydrophobic Blocks

Abstract

To design stable biodegradable micelles with a size smaller than 20 nm, the self-assembly of methoxypoly(ethylene glycol)-b-oligocaprolactones (mPEG-b-OCLs), and the effect of OCL block length and terminal derivatization with an aromatic group were studied. The studied oligomers consisted of an mPEG block with a molecular weight of 750 Da and a monodisperse OCL block of 1−7 units with a hydroxyl end group that was either unmodified, benzoylated or naphthoylated. They were prepared by preparative HPLC of the polydisperse block oligomers. Differential scanning calorimetry demonstrated that the two blocks were phase separated and crystallized separately. These block oligomers formed small and almost monodisperse oligomeric micelles with a hydrodynamic diameter of 8−15 nm, which could be tailored by the size of the hydrophobic block. The critical aggregation concentration (CAC) of the unmodified mPEG-b-OCLs was 0.03−4 mg/mL, and it decreased with increasing length of the OCL chain. End group modification resulted in an extensive reduction of the CAC to values as low as 0.003 mg/mL. This is expected to result in a better stability of these oligomeric micelles toward dilution upon intravenous administration, which makes these modified mPEG-b-OCLs very promising candidates for drug delivery purposes.

Polymeric micelles: authoritative aspects for drug delivery

“…The reduction in CMC can be achieved by either of the two approaches: adjusting the sizes of the blocks such that the polymer becomes more hydrophobic or adjusting the nature of the hydrophobic block. Higher hydrophobicity can be achieved with introduction of a larger hydrophobic block or a smaller hydrophilic block, thereby resulting in a reduced CMC value [224]. Alteration in the nature of the hydrophobic block is possible by means of chemical modification of the hydrophobic block, e.g.…”

Hydrolysable core-crosslinked thermosensitive polymeric micelles: Synthesis, characterisation and in vivo studies

“…The micelles are mainly kept together either by hydrophobic forces between the hydrophobic blocks (e.g. polylactide [5,6], polycaprolactone [7,8], poly(meth)acrylamides [9][10][11]) of amphiphilic block copolymers or by electrostatic interactions, e.g., between negatively charged DNA and cationic block copolymers [4]. PM have attractive features for drug delivery purposes because their core can accommodate various compounds (e.g.…”

“…in the form of stereocomplexes) in their cores [21,22]. Modifying the core-forming block with aromatic moieties also stabilised (mainly via p-p interactions) micellar morphologies as was indicated by a substantially decreased CMC [7,8]. Covalently shell crosslinked PM were prepared by chemical or photoinduced reactions [26][27][28][29][30] while also the intermediate layer (moiety between the hydrophobic and hydrophilic block) was exploited to crosslink PM [31][32][33].…”

Electrostatic interactions between polyglutamic acid and polylysine yields stable polyion complex micelles for deoxypodophyllotoxin delivery

“…As a result, micelles exhibited high stability against sodium dodecyl sulfate (SDS) surfactant as well as organic solvents, and drug loading efficiency and thermodynamic stability were significantly enhanced against dilution. In addition to chemical cross-linking, the stability of micelles can also be improved by introducing physical interactions such as isomer interactions, 19 π-π interactions, 20 and electrostatic reactions 21 inside the micelle core. Among all the interactions, the electrostatic reaction is an ideal option as it can deliver small and large charged molecules by reacting with block ionomers to form a stable core.…”