Retinol-Containing Graft Copolymers for Delivery of Skin-Curing Agents

Abstract

The new polymeric systems for delivery in cosmetology applications were prepared using self-assembling amphiphilic graft copolymers. The synthesis based on “click” chemistry reaction included grafting of azide-functionalized polyethylene glycol (PEG-N3) onto multifunctional polymethacrylates containing alkyne units. The latter ones were obtained via atom transfer radical polymerization (ATRP) of alkyne-functionalized monomers, e.g., ester of hexynoic acid and 2-hydroxyethyl methacrylate (AlHEMA) with methyl methacrylate (MMA), using bromoester-modified retinol (RETBr) as the initiator. Varying the content of alkyne moieties adjusted by initial monomer ratios of AlHEMA/MMA was advantageous for the achievement of a well-defined grafting degree. The designed amphiphilic graft copolymers P((HEMA-graft-PEG)-co-MMA), showing tendency to micellization in aqueous solution at room temperature, were encapsulated with arbutin (ARB) or vitamin C (VitC) with high efficiencies (>50%). In vitro experiments carried out in the phosphate-buffered saline solution (PBS) at pH 7.4 indicated the maximum release of ARB after at least 20 min and VitC within 10 min. The fast release of the selected antioxidants and skin-lightening agents by these micellar systems is satisfactory for applications in cosmetology, where they can be used as the components of masks, creams, and wraps.

4-n-Butylresorcinol-Based Linear and Graft Polymethacrylates for Arbutin and Vitamins Delivery by Micellar Systems

“…The degree of hydrophilicity was controlled by an appropriate selection of the initial proportions of the MMA or HEMA and MPEGMA comonomers (50/50 and 75/25). The presence of hydroxyl groups in the P(HEMA-co-MMA) and P(HEMA-co-MPEGMA) copolymers is observed in the FT-IR spectra (Figure 3a,b), given as broad peak at 3200-3500 cm −1 in contrast to the copolymer without HEMA units such as P(MMA-co-MPEGMA) (Figure 3c), which is in agreement with analogous polymethacrylates [43,44]. MPEGMA containing copolymers exhibited a high intensity extended band in the range of 1050-1150 cm −1 representing C-O-C stretching vibrations (Figure 3b,c).…”

“…This resulted in the RET functionalized copolymers forming smaller micelles than those without RET moieties. Here, the investigated ARB loaded micelles of the "click" grafted copolymer with 4nBRE moiety localized in the middle of V-shaped chains (Vc) show a similar level of a hydrophilic fraction [44] and have smaller D h , probably due to non-linear topology, than previously studied analogous system with of ARB and RET functionalized copolymer.…”

“…The conversion of the monomers into copolymers was calculated from the 1 H NMR spectrum by integrating the resonances related to unreacted monomer and formed polymer. P(AlHEMA-co-MMA) and P(HEMA-co-MMA) protons which represented methylene groups (CH 2 = mon : 5.6 and 6.2 ppm; -COO-CH 2polym : 4.1-4.2 ppm) and protons in methoxy groups (-OCH 3mon : 3.75 ppm, -OCH 3polym : 3.6 ppm) were used to evaluate the conversion of AlHEMA or HEMA and MMA, respectively [44]. For other copolymers the MPEGMA conversion was determined via integration of isolated resonances assigned to CH 2 = in the monomer (A m : 6.03 ppm) and -OCH 2 CH 2 O-in the polymer (C p : 3.52 ppm) [48] ( Figure 4).…”

“…The reaction was then carried out at room temperature for 2 days and then the mixture was extracted three times with methylene chloride/H 2 O. The brown liquid obtained after evaporation of the organic fraction was dried to constant mass [44]. Yield: 61%.…”

“…The measurements were completed in acetone and optimizing the temperature of the injector and detector to 250 • C, initial and final temperature of column 40 and 200 • C, respectively. The integration of signals at defined retention times for MPEGMA (1.8 min), MMA (2.3 min), HEMA (8.5 min), and AlHEMA (10.0 min) were compared to the retention time of anisole (4.9 min), allowing us to calculate monomer conversion [43,44]. Mass spectrometry (MS, Xevo G2 QTof, Waters Corporation, Milford, UT, USA) was used to confirm the molecular masses of the modified 4nBRE and functionalized HEMA.…”