Amphiphilic Co-polypeptides Self-Assembled into Spherical Nanoparticles for Dermal Drug Delivery

Abstract

Poly­(l-glutamic acid)-b-poly­(N γ-acetyl-l-2,4-diaminobutyric acid), P­(Glu-b-NADA), amphiphilic block-co-polypeptides with different hydrophobic/hydrophilic ratios were synthesized as drug carriers for dermal delivery. The block-co-polypeptides were prepared using ring-opening polymerization (ROP) of γ-benzyl l-glutamate N-carboxyanhydride and polycondensation of the activated urethane derivative of N γ-acetyl-l-2,4-diaminobutyric acid. Structures and conjugations of two blocks were successfully confirmed by 1H NMR, FTIR, DOSY NMR, GPC, and TGA. The nanocarriers were loaded with 5,10,15,20-tetrakis­(3-hydroxyphenyl)­porphyrin (m-THPP), a close congener of the approved photosensitizer 5,10,15,20-tetrakis­(3-hydroxyphenyl)­chlorin (m-THPC, temoporfin), and the loading capacity was found to be dependent on the composition of the block-co-polypeptides. Among the synthesized polymers, P­(Glu55-b-NADA20) with moderate hydrophobic content showed the highest drug loading capacity of 4 wt % and self-aggregated into spherical nanoparticles with a size of 180–200 nm, which was confirmed by TEM and DLS. In an in vitro drug release study, P­(Glu55-b-NADA20) could release m-THPP in a controllable manner. Furthermore, the synthesized polymer P­(Glu55-b-NADA20) did not show high toxicity against HaCaT and HeLa cells up to 1000 and 500 μg mL–1, respectively, in an in vitro cell viability assay. Finally, it was shown in an ex vivo skin penetration study that the ionic amphiphilic block co-polypeptide enhanced the m-THPP penetration into human skin compared to base cream up to a factor of 12. m-THPP was released from P­(Glu55-b-NADA20) to the viable epidermis while the polymer was deposited in the skin’s stratum corneum. Taking advantage of its excellent biodegradability, the low cytotoxcity, and efficient skin penetration, the synthesized block-co-polypeptide has the potential for future topical delivery systems.

Efficient skin interactions of graphene derivatives: challenge, opportunity or both?

“…Preparation of skin samples for transmission electron microscopy (TEM). Aer application of the graphene sheets according to our previously reported paper, 55 skin samples were xed in Karnovsky solution (7.5% glutaraldehyde and 3% paraformaldehyde in 0.1 M cacodylate buffer; all Roth, Karlsruhe, Germany) overnight, washed in 0.1 M cacodylate buffer (cacodylic acid sodium salt trihydrate, Roth, Karlsruhe, Germany), and incubated in 1% osmium tetroxide (Electron Microscopy Sciences, Hateld, PA, USA) for 4 h. Samples were dehydrated in an ascending series of ethanol followed by the intermedium propylene oxide (1,2-epoxypropan; VWR, Germany). The specimens were subsequently embedded in a mixture of Agar 100 (epoxy resin), DDSA (soener), MNA (hardener) and DMP 30 (catalyst) (all: Agar Scientic; Stansted, UK).…”

Synthesis of C3-symmetric star shaped amphiphiles for drug delivery applications

“…The ex vivo experiment was performed according to our previously published work and conventional base cream containing 0.001% w/w Nile red served as a control. 40 Briefly, skin from three different healthy donors was cut with dimensions of 1.5 Â 1.5 cm 2 and fixed on the surface of Styrofoam blocks using needles. The prepared samples were kept in a box with wet towels to avoid dryness of treating skin samples.…”

The Photosensitizer Temoporfin (mTHPC) – Chemical, Pre‐clinical and Clinical Developments in the Last Decade†‡

“…However, the combination of peptides and polymers has also been exploited as drug transporters for temoporfin. Ahmadi et al (103) used amphiphilic block-copolypeptides as carriers for dermal drug delivery, again taking the temoporfin congener mTHPP as a model drug. In another approach polymer-block-peptides were exploited for drug delivery.…”

“…Ahmadi et al . (103) used amphiphilic block‐ co ‐polypeptides as carriers for dermal drug delivery, again taking the temoporfin congener m THPP as a model drug. In another approach polymer‐ block ‐peptides were exploited for drug delivery.…”