D-α-Tocopherol-Based Micelles for Successful Encapsulation of Retinoic Acid

Abstract

All-trans-retinoic acid (ATRA) represents the first-choice treatment for several skin diseases, including epithelial skin cancer and acne. However, ATRA’s cutaneous side effects, like redness and peeling, and its high instability limit its efficacy. To address these drawbacks and to improve ATRA solubilization, we prepared ATRA-loaded micelles (ATRA-TPGSs), by its encapsulation in D-α-tocopheryl-polyethylene-glycol-succinate (TPGS). First, to explore the feasibility of the project, a solubility study based on the equilibrium method was performed; then, six ATRA-TPGS formulations were prepared by the solvent-casting method using different TPGS amounts. ATRA-TPGSs showed small sizes (11–20 nm), low polydispersity, slightly negative zeta potential, and proved good encapsulation efficiency, confirmed by a chemometric-assisted Fourier transform infrared spectroscopy (FTIR) investigation. ATRA-TPGS stability was also investigated to choose the most stable formulation. Using Carbopol® 980 as gelling agent, ATRA-TPGS-loaded gels were obtained and analyzed for their rheological profiles. Ex vivo release studies from ATRA-TPGSs were performed by Franz cells, demonstrating a permeation after 24 h of 22 ± 4 µ cm−2. ATRA-TPGSs showed enhanced cytotoxic effects on melanoma cells, suggesting that these formulations may represent a valid alternative to improve patient compliance and to achieve more efficacious therapeutic outcomes.

Increased Water-Solubility and Maintained Antioxidant Power of Resveratrol by Its Encapsulation in Vitamin E TPGS Micelles: A Potential Nutritional Supplement for Chronic Liver Disease

“…Values of S l /S f~1 .0 ± 0.3 indicate that the initial size is maintained, whereas larger values approaching 2 or more suggest a significant aggregation of nanoparticles [41]. Indeed, as recently reported, these systems may not need any cryoprotectant adjunct, as already demonstrated in previous works [19,42].…”

“…In addition, in this study, the concentration of TPGS providing high encapsulation efficiency is extraordinarily low. Indeed, the TPGS amounts used for RES encapsulation ranged from 2 mg/mL to 14 mg/mL (0.2–1.4 w / v %), which is far lower compared to those suitable for retinoic acid encapsulation [ 19 ], etoposide [ 25 ], although it is comparable to the effect of TPGS on the solubility of lopinavir [ 23 ] and paclitaxel [ 22 ].…”

“…The RES thermogram shows the characteristic endothermic peak at 268 °C due to RES’s melting point. TPGS shows an endothermic peak at 32 °C [ 19 ]. The DSC thermograms of the RES-TPGS lyophilized formulation showed only the melting peak of the TPGS, indicating the absence of the drug in the crystalline state, and suggesting that the encapsulated drug was in an amorphous state of a solid molecular dispersion into the TPGS core.…”

“…RES micelles were also prepared using the solution casting method, according to the previously published procedure with slight modifications [ 19 ]. The same preparative mixtures described in the previous subsection were employed and solubilized in 6 mL of ethanol; in the case of blanks, only TPGS was included.…”

“…Based on the above, we chose to combine the properties of TPGS as a functional food supplement with its capability to encapsulate lipophilic substances such as RES, with the aim of optimizing nutritional support in children with chronic liver disease. TPGS has been widely studied as an absorption enhancer and emulsifier and it has already been shown to act simultaneously as a nanocarrier and as a permeation enhancer [ 19 ]. TPGS is capable of self-assembling in water above its critical micellar concentration (CMC), equal to 0.02 wt %, in nanosized aggregates.…”