Dendrimer-conjugated isotretinoin for controlled transdermal drug delivery

Abstract

Background In the present study, we aimed to develop a novel isotretinoin delivery model for treating skin diseases, revealing its potential advantages in drug delivery and targeted therapy. Using a self-assembly strategy, we grafted a dendrimer, based on a well-defined branched structure for nanomedical devices, with a well-defined nanoarchitecture, yielding spherical, highly homogeneous molecules with multiple surface functionalities. Accordingly, a self-assembled dendrimer-conjugated system was developed to achieve the transdermal delivery of isotretinoin (13cRA-D). Results Herein, 13cRA-D showed remarkable controlled release, characterized by slow release in normal tissues but accelerated release in tissues with low pH, such as sites of inflammation. These release characteristics could abrogate the nonteratogenic side effects of isotretinoin and allow efficient skin permeation. Moreover, 13cRA-D exhibited high therapeutic efficacy in acne models. Based on in vitro and in vivo experimental results, 13cRA-D afforded better skin penetration than isotretinoin and allowed lesion targeting. Additionally, 13cRA-D induced minimal skin irritation. Conclusion Our findings suggest that 13cRA-D is a safe and effective isotretinoin formulation for treating patients with skin disorders. Graphical Abstract

Deep eutectic solvent self-assembled reverse nanomicelles for transdermal delivery of sparingly soluble drugs

“…The IMQ-induced psoriatic mouse model was established to evaluate the therapeutic efficacy of the formulation [ 32 ]. Based on the above results, 10% DES (4:6)-RM was selected as the topical delivery carrier of TA, namely TA@DES-RM (containing 0.1% TA, w/w).…”

Recent Approaches for the Topical Treatment of Psoriasis Using Nanoparticles

“…These advantageous release characteristics could reduce the teratogenic side effects of isotretinoin, facilitating effective skin penetration. In vitro and in vivo studies showed that dendrimers improved the penetration rate of the isotretinoin to the lower layers of the skin, thus targeting lesions more effectively [ 154 ]. Table 9 summarizes the above-mentioned dendrimers.…”

Liposomes and Other Nanocarriers for the Treatment of Acne Vulgaris: Improved Therapeutic Efficacy and Skin Tolerability

“…Dendrimers have attracted significant attention in various fields, including drug delivery, due to their unique properties, such as a uniform size, well-defined architecture, and the ability to encapsulate drugs or other molecules. Dendrimers have hydrophobic and hydrophilic exteriors, similar to lipid bilayer membranes, enabling them to encapsulate different drugs [ 65 ]. We should distinguish between poly-(amidoamine) (PAMAM) dendrimers, showing their drawback of leading to biodegradation products—“acrylates”, and the peptide dendrimers, which show a lower toxicity, as they degrade to harmless amino acids.…”

“…A self-assembled dendrimer-conjugated system was developed to achieve the enhanced percutaneous penetration of isotretinoin [ 65 ]. The authors reported that the isotretinoin-loaded dendrimers showed a remarkable controlled release, characterized by a slow release in normal tissues but accelerated release in tissues with low pH, such as sites of inflammation.…”