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

Abstract

This communication is dedicated to Late Yogesh Chamkure for his forever memories in Dr Rakesh K. Sharma's research laboratory.Poor drug solubility and oral bioavailability is a significant challenge with many effective drug candidates. Pluronic micelles are effective solutions for improved solubility, stability, and delivery of the hydrophobic drug to the right area, at the right time, and in the right amount. Solubilization of three drugs, namely curcumin (CUR), quercetin (QCN), and lamotrigine (LTG), were explored using Pluronics with varying molecular characteristics. All the drugs showed better solubility in Pluronic solutions. The tendency of augmentation in solubility was QCN > CUR > LTG. Results showed better solubilization of drugs in Pluronics which form micelles and have low CMTs. With an objective to enhance the oral bioavailability of drugs, the drug-loaded Pluronic P123 nanomicelles (PLC for CUR, PLQ for QCN, and PLL for LTG) have been prepared and characterized using UV-VIS, DLS, SANS, CPT, and TEM measurements. The drug-loaded P123 nanomicelles having particle sizes range from 18 to 22.5 nm and spherical in shapes. In the in-vitro release study, CUR and QCN showed slow release,while LTG exhibited a faster release profile. The PLC and PLQ assessed their anti-oxidant potential had confirmed the oxidation resistance more significantly than the free drug. Considering the pharma uses of CUR, QCN, and LTG drugs and observing the application of Pluronics in drug delivery systems, the present work facilitates insight into the possible formulations of these drugs.

Block Copolymer Encapsulation of Disarib, an Inhibitor of BCL2 for Improved Chemotherapeutic Potential

“…The intense peak obtained for P123D compared to the Disarib molecule indicates that the drug molecule shifted from the bulk phase to the micellar phase, and it provides evidence for the fact that the incorporation of the hydrophobic drug was better in P123. The results were in agreement with previous reports. , …”

“…P123 has 69 propylene oxide units in a total mass of molecules, and it results in the high hydrophobicity of the Pluronic micelles. Furthermore, P123 has high surface activity and low CMC (critical micelle concentration), which makes it an excellent solubilizer of hydrophobic drugs …”

“…The results were in agreement with previous reports. 52,53 To evaluate the solubility of Disarib in aqueous medium, a certain amount of Disarib and P123D was dissolved in water, and the increase in the intensity of P123D's absorption peak in comparison to Disarib in water indicated an enhanced solubility of Disarib (Figure 2B). As per the similar works reported, Pluronic micelles are capable of solubilizing and encapsulating poorly soluble drugs due to the hydrophobic forces present in them.…”

“…Furthermore, P123 has high surface activity and low CMC (critical micelle concentration), which makes it an excellent solubilizer of hydrophobic drugs. 53 3.1.2. FTIR and NMR Studies.…”