Biodegradable self-assembly micelles significantly enhanced the solubility, biological stability and in vivo antitumor efficacy of Hexylselen

Abstract

Soluplus increased the aqueous solubility of Hexylselen (CPD-3B) by about 3000-fold forming nano-sized micelles, significantly enhanced the stability in blood and liver microsomes and improved the in vivo bioavailability and antitumor efficacy.

Soluplus®-based dissolving microarray patches loaded with colchicine: towards a minimally invasive treatment and management of gout

“…28 In comparison to classical solubilizers such as Cremophore RH40 and Solutol HS15, Soluplus® can function as a matrix polymer to stabilise formulation, as well as an serving the role of a polymeric solubilizer via micellar solubilisation when present an aqueous milieu. [29][30][31][32] Owing this characteristic, Soluplus® has been widely used as film former with addition of plasticizer to reduce the brittleness. 33,34 Therefore, owing to its mechanical properties, biocompatibility as well as biodegradability, Soluplus® may serve as potentially novel material to fabricate dissolving MAPs.…”

Self-Assembled Micellar Glutaminase Allosteric Inhibitor for Effective Therapeutic Intervention

“…For CPD 23@SOL PM, characteristic peaks at 2 θ angles of 7.6302 °, 16.1027 ° and 18.8456 ° still appeared, which were similar to those sharp peaks in CPD 23 powder, demonstrating that CPD 23 kept crystalline state when it was only physically mixed with SOL, and also when given inadequate SOL as our previous report showed. 17 Conversely, these prominent peaks essentially disappeared in CPD 23@SOL (1:20) SD after the formulating preparation and the resulting flat peaks were similar to those in SOL, suggesting that the crystalline CPD 23 was converted to the amorphous form. 26 Therefore, CPD 23 was verified to show amorphous state with SOL in solid dispersion.…”

“…Multiple drug delivery systems (DDS) and commonly-used excipients have been explored for potent allosteric inhibitors including the 1,3,4-Selenadiazole compound (CPD 23), but only limited solubility improvement has been achieved. 10 , 17 Interestingly, Soluplus ® has many advantageous and versatile properties, 18 so we investigated SOL as the excipient to formulate nano-micelles to address the solubilization problem.…”

“…The thin film dispersion method was used to prepare CPD 23@SOL micelles according to the previous report. 17 Briefly, CPD 23 and Soluplus ® were first completely solubilized in mixture of dichloromethane and ethanol (1:4, v/v) by ultrasonication, then evaporated to remove the organic solvents under a vacuum of −0.1 MPa at 40–42 °C until dry, and the obtained thin layer was washed and hydrated with sterile saline (0.9% NaCl solution) to form CPD 23@SOL micelles. Several mass ratios of CPD 23 and Soluplus ® were used for preparation, and the most stable formulation was selected by comparing the amount of prescription from micelles in 24 hours.…”

“…15,16 However, by forming self-assembly micelles using the widely used polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (PVCap-PVA-PEG, 13%-57%-30%, respectively) graft copolymer, named Soluplus ® or SOL, the Hexylselen@SOL micelles have achieved significantly improved solubility, biological stability, in vivo bioavailability and antitumor efficacy. 17 This indicated that the micelles are suitable as the delivery system for seleniumcontaining KGA allosteric inhibitors in practice.…”