Berberine-Loaded Thiolated Pluronic F127 Polymeric Micelles for Improving Skin Permeation and Retention - PubMed (original) (raw)

Berberine-Loaded Thiolated Pluronic F127 Polymeric Micelles for Improving Skin Permeation and Retention

Jiangxiu Niu et al. Int J Nanomedicine. 2020.

Abstract

Background: Challenges associated with local antibacterial and anti-inflammatory drugs include low penetration and retention of drugs at the expected action site. Additionally, improving these challenges allows for the prevention of side effects that are caused by drug absorption into the systemic circulation and helps to safely treat local skin diseases.

Methods: In the current study, we successfully prepared a thiolated pluronic F127 polymer micelles (BTFM), which binds to keratin through a disulphide bond, to produce skin retention. In addition, the small particle size of polymer micelles promotes the penetration of carriers into the skin. The current study was divided into two experiments: an in vitro experiment; an in vivo experiment that involved the penetration of the micelle-loaded drugs into the skin of rats, the skin irritation test and the anti-inflammatory activity of the drug-loaded micelles on dimethyl benzene-induced ear edema in mice.

Results: Results from our in vitro transdermal experiment revealed that the amount of drug absorbed through the skin was decreased after the drug was loaded in the BTFM. Further, results from the vivo study, which used fluorescence microscopy to identify the location of the BTFM after penetration, revealed that there was strong fluorescence in the epidermis layer, but there was no strong fluorescence in the deep skin layer. In addition, the BTFM had a very good safety profile with no potentially hazardous skin irritation and transdermal administration of BTFM could significantly suppress ear edema induced by dimethyl benzene. Therefore, these findings indicated that BTFM reduced the amount of drug that entered the systemic circulation. Our results also demonstrated that the BTFM had a certain affinity for keratin.

Conclusion: Our experimental results suggest that the BTFM may be an effective drug carrier for local skin therapy with good safety profile.

Keywords: F127 polymeric micelles; berberine; cysteine; skin permeation and retention.

© 2020 Niu et al.

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Conflict of interest statement

The authors report no conflicts of interest for this work.

Figures

Figure 1

Figure 1

Representation of the strategy of developing berberine-loaded cysteine-modified pluronic F127 micelle for improving skin permeation and retention.

Figure 2

Figure 2

(A) Synthetic scheme. (B) 1H NMR spectrum of the F127-cysteine. (C) 13C NMR spectrum of the F127-cysteine.

Figure 3

Figure 3

Effects of different proportions of drugs and carriers on encapsulation efficiency and drug loading (n=3).

Figure 4

Figure 4

(A) Particle size and distribution of BTFM measured by DLS. (B) SEM images of BTFM.

Figure 5

Figure 5

(A) TEM observation of the BTFM without adding keratin solution. (B) TEM observation of the interaction between BTFM and keratins (keratin solution was mixed with BTFM in equal volume and incubated in a shaker at 37 °C and 100 rpm for 1 h).

Figure 6

Figure 6

DSC thermograms of physical mixture of berberine and cysteine conjugated pluronic F127, cysteine conjugated pluronic F127, lyophilized BTFM as well as berberine.

Figure 7

Figure 7

X-ray diffraction patterns of cysteine conjugated pluronic F127, berberine as well as lyophilized BTFM.

Figure 8

Figure 8

FTIR spectra of physical mixture of berberine and cysteine conjugated pluronic F127, blank micelles, lyophilized BTFM as well as berberine.

Figure 9

Figure 9

(A) In vitro profile of berberine release (mean±SD, n=3) from berberine solution and BTFM in phosphate buffer solution of pH 7.4 and pH 5.5. (B) In vitro permeation of berberine from BFM, BTFM and drug solution across rat skin in pH 7.4. (C) Berberine retention in rat skin after exposure to BFM, BTFM and drug solution for 24 h (data given as the mean ± SD, n=3; *p < 0.05 versus berberine solution).

Figure 10

Figure 10

Fluorescence microscopic images of longitudinal-section of the living rats skin from the permeation study of FFM and FTFM.

Figure 11

Figure 11

The zeta potential and mean particle size of the mixture of keratin and BTFM in various volume ratios at pH 7.4 (n=3).

Figure 12

Figure 12

The contact angle of different formulation to keratins (data given as the mean ± SD, n=3; *p < 0.05 versus BFM).

Figure 13

Figure 13

Acute dermal irritation/corrosion test. Mice skin appearance after 1 h, 4 h, 24 h and 72 h of observation. First line: mice treated with physiological saline (control group). Second line: mice treated with berberine solution. Third line: mice treated with BFM (berberine loaded pluronic F127 micelles). Fourth line: mice treated with BTFM (berberine loaded thiolated pluronic F127 polymeric micelles). Experiments were done on 6 animals for each group.

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