Improved Ex Vivo Transcutaneous Permeation of Diclofenac from Solid Lipid Nanoparticles in the Presence of Novel Long-Chain Alkyl Esters of PABA

Abstract

The current study aimed to evaluate long-chain alkyl esters of p-amino benzoic acid (PABA) as possible new class of permeation enhancers. In this study we have synthesized long-chain alkyl esters of PABA (decyl, dodecyl, and tetradecyl) by a novel and facile method in our laboratory. The PABA derivatives were incorporated into solid lipid nanoparticles and characterized for size, zeta potential and entrapment efficiency. In vitro permeation study was carried out using rat abdominal skin and permeation enhancement was assessed from the permeation parameters (flux, permeability coefficient, and enhancement ratio). Among the formulations tested, Dodecyl PABA containing solid lipid nanoparticles (SLN) has shown a significant enhancement in the permeation of diclofenac compared to control and other PABA derivatives containing solid lipid nanoparticles. The increase in permeation parameters clearly indicates the potential of PABA derivatives as a novel amphiphile that can be explored as a new class of permeation enhancers in topical drug delivery.

Keywords:

• Diclofenac
• flux
• long-chain alkyl esters of PABA
• solid lipid nanoparticles
• transcutaneous

Notes

*All quantities are in mg except polysorbate 80 (% w/v).

GMS: Glyceryl monostearate; PABA: p-amino benzoic acid; NC: Control solid lipid nanoparticles; NDP, NDDP, and NTDP represents solid lipid nanoparticles with decyl PABA, dodecyl PABA, and tetradecyl PABA respectively.

PI: polydispersity index.

NC: Control solid lipid nanoparticles; NDP, NDDP and NTDP represents solid lipid nanoparticles with decyl PABA, dodecyl PABA, and tetradecyl PABA, respectively.

NC: Control solid lipid nanoparticles; NDP, NDDP and NTDP represents solid lipid nanoparticles with decyl PABA, dodecyl PABA, and tetradecyl PABA, respectively.

Q24-cumulative amount permeated per unit area after 24 hours, Jmax = maximum flux, Jss = steady state flux, Kp = permeability coefficient, ER = enhancement ratio.

1, 2, 3, and 4 indicates NC, NDP, NDDP, and NTDP, respectively.

a, b represents p < 0.001, 0.05, respectively.