Delivery and diffusion of retinal in dermis and epidermis through the combination of prodrug nanoparticles and detachable dissolvable microneedles

Drug Deliv Transl Res. 2022 Nov;12(11):2751-2761. doi: 10.1007/s13346-022-01136-3. Epub 2022 Feb 21.

Abstract

To minimize chemical degradation of retinal, we graft this aldehyde on chitosan chains to make them self-assemble into pro-retinal nanoparticles (PRNs), which we then load into detachable dissolvable microneedles (DDMNs) made of 1:1 (by weight) hyaluronic acid/maltose. The presence of PRNs in the hyaluronic acid-maltose needle matrix also helps improve the microneedles' mechanical strength. Ex vivo administration of PRN-loaded DDMNs on fresh porcine ear skin shows, as observed by stereomicroscopic and confocal fluorescence microscopic analyses of the cross-sectioned tissue pieces, complete deposition followed by dissolution of the needles and diffusion of the PRNs in epidermis and dermis. Rats administered with a single dose of PRN-loaded DDMNs show significantly increased epidermal thickness as compared to rats administered with control DDMNs (no PRN). Both the PRN-loaded DDMNs and the control DDMNs produce no skin irritation in rats.

Keywords: Dermis; Drug release; Microneedles; Retinaldehyde; Stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Aldehydes
  • Animals
  • Chitosan*
  • Dermis
  • Drug Delivery Systems
  • Epidermis
  • Hyaluronic Acid
  • Maltose
  • Nanoparticles*
  • Needles
  • Prodrugs*
  • Rats
  • Swine

Substances

  • Aldehydes
  • Prodrugs
  • Maltose
  • Hyaluronic Acid
  • Chitosan