Diabetes mellitus is a chronic manifestation
characterized by high
levels of glucose in the blood resulting in several complications
including diabetic wounds and ulcers, which predominantly require
a longer duration of treatment and adversely affect the quality of
life of the patients. Nanotechnology-based therapeutics (both intrinsic
and extrinsic types) have emerged as a promising treatment in diabetic
foot ulcer/chronic wounds owing to their unique characteristics and
specific functional properties. In this review, we have focused on
the significance of the use of lipids in the healing of diabetic ulcers,
their interaction with the injured skin, and recent trends in lipid-based
nanocarriers for the healing of diabetic wounds. Lipid nanocarriers
are also being investigated for gene therapy in diabetic wound healing
to encapsulate nucleic acids such as siRNA and miRNA, which could
silence the expression of inflammatory cytokines overexpressed in
chronic wounds. Additionally, these are also being explored for encapsulating
proteins, peptides, growth factors, and other biological genetic material
as therapeutic agents. Lipid-based nanocarriers encompassing a wide
variety of carriers such as liposomes, niosomes, ethosomes, solid
lipid nanoparticles, and lipidoid nanoparticles that are explored
for the treatment of foot ulcers supplemented with relevant research
studies have been discussed in the present review. Lipid-based nanodrug
delivery systems have demonstrated promising wound healing potential,
particularly in diabetic conditions due to the enhanced efficacy of
the entrapped active molecules.
Several
drug–fatty acid (FA) prodrugs have been reported
to exhibit desirable physicochemical and pharmacological profile;
however, comparative beneficial effects rendered by different FAs
have not been explored. In the present study, four different FAs (linoleic
acid, oleic acid, palmitic acid, and α-lipoic acid) were selected
based on their chain length and degree of unsaturation and conjugated
to Lisofylline (LSF), an antidiabetic molecule to obtain different
drug–FA prodrugs and characterized for molecular weight, hydrophobicity,
purity, self-assembly, and efficacy in vitro and in vivo in type 1 diabetes model. Prodrugs demonstrated
a 2- to 6-fold increase in the plasma half-life of LSF. Diabetic animals
treated with prodrugs, once daily for 5 weeks, maintained a steady
fasting blood glucose level with a significant increase in insulin
level, considerable restoration of biochemical parameters, and preserved
β-cells integrity. Among the different LSF-FA prodrugs, LSF-OA
and LSF-PA demonstrated the most favorable physicochemical, systemic
pharmacokinetic, and pharmacodynamic profiles.
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