Incorporation of Lamotrigine Drug in the PEO–PPO–PEO Triblock Copolymer (Pluronic F127) Micelles: Effect of Hydrophilic Polymers

Abstract

The hydrophobic drug Lamotrigine (LTG) shows low bioavailability after oral administration. Work has been performed to improve the aqueous solubility of LTG using the micelles of amphiphilic block copolymers. Polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymers (PEO-PPO-PEO), known as Pluronic Ò , have been the subject of current interest due to the versatile structural possibilities of varying PEO/PPO ratios. Incorporation of LTG in the aqueous micellar solutions of Pluronic Ò F127 was investigated using UVvisible spectroscopy. The shapes and size of the micelles with and without LTG have been ascertained using dynamic light scattering and small angle neutron scattering experiments. Results show increase in the Pluronic Ò micellar size with hard sphere radius with the incorporation of LTG. The effect of hydrophilic polymers (PEG1500 and F68) on the LTG-incorporated Pluronic Ò F127 micelles was also studied and found inefficient for enhancement of the solubility of LTG. Solid forms of LTG-incorporated Pluronic Ò F127 micelles with and without hydrophilic polymers, coded as LPMs, were successfully prepared through the thin-film hydration method. Fourier transform infrared spectroscopy, X-ray diffraction spectroscopy and thermogravimetric analysis have been used to ensure the compatibility of the LTG with Pluronic Ò F127 micelles in prepared LPMs. All the LPMs showed good incorporation efficiency, loading capacity and the sustained release profile of LTG. Results showed no specific improvement with the addition of hydrophilic polymers in the studied concentration range.

Coarse-Grained Molecular Dynamic and Experimental Studies on Self-Assembly Behavior of Nonionic F127/HS15 Mixed Micellar Systems

“…During this spontaneous aggregation process, the PPO chains were rapidly orientated toward the hydrophilic shell of HS15 clusters, wrapped around HS15 clusters, and a new type of aggregate formed with a hydrophilic “PEO palisade layer” shell (green beads, Figure a), interior HS15 spheres (red beads, Figure c), and a continuous channel in between (yellow and gray beads, Figure b). This aggregate is closer to the “multicompartment” structure, different from the simple “core–shell” models generally described as the hydrophobic chains of amphiphilic molecules in the inner core of the micelle and the polar head groups at the outer shell. − We postulate that this is probably because of the difference of hydrophobicity between these chains. Additionally, we can know that the assembly behavior for system III occurs quickly, and the shape of this micellar system was relatively stable, which can partly derive from the diameter of the aggregate having changed not much after 200 ns (Figure S1 in the Supporting Information).…”

Enhanced Solubility and Oral Bioavailability of Hydrophobic Drugs Using Pluronic Nanomicelles: An In‐Vitro Evaluation

“…where R is the gas constant, T is the working temperature (in Kelvin), and P is the partition coefficient. [52][53][54] The calculated values of P and ΔG°for all the P123 nanomicellar solutions were listed in Table 2.…”

Amphiphilic Micelles as Superior Nanocarriers in Drug Delivery: from Current Preclinical Surveys to Structural Frameworks

“…The micelles based on block copolymers have been usually used as drug delivery vehicles. [161][162][163] Similarly pluronics (copolymers of polyethylene oxide) based micelles have been approved for pharmaceutical uses [164][165][166][167] and are promising owing to their efficient drug loading abilities and phenomenal micellar features. [50] These are accessible at large scale commercially with changing polyethylene oxide and polypropylene oxide block chains and ratios.…”