Therapeutic potential of quercetin in diabetic foot ulcer: Mechanistic insight, challenges, nanotechnology driven strategies and future prospects

Diabetic foot ulcer (DFU) is a complicated condition with symptoms of neuropathic pain, immunological and biochemical impairments promotes delayed wound healing processes and foot amputations. Currently available therapeutic options for the management of DFU are excruciating and expensive; hence affect the global socioeconomic burden. An optimal therapy for DFU should exhibit easy acceptability, reliability and cost-efficient feature. Interestingly, quercetin displays excellent antidiabetic, anti-inflammatory, antioxidant, antimicrobial and wound healing properties which makes it a promising molecule for the management of diabetic wounds. It enhances the process of angiogenesis by activating multiple factors such as Msr-1, Arg-1, VEGF-α, HO-1, PECAM-1 as well as known for its action on PI3K/Akt/eNOS pathway to promote the cell proliferation, collagen deposition and angiogenesis. Despite numerous therapeutic benefits of quercetin, its use in DFU is limited owing to pharmaceutical challenges such as low aqueous solubility (0.48 ± 0.1 μg/mL), poor permeability (log P 1.82 ± 0.3), instability in gastro-intestinal tract, average terminal half-life (3.5 h), poor oral bioavailability (4%) and extensive first past metabolism. Further, lacking of clinical data and insufficient understanding of mechanism of action have listed the quercetin only as a complementary and alternative medicine or a nutraceutical. Therefore, in present review, we have discussed complete etiology of diabetic foot, available therapies and their shortcomings. In addition, an attempt has also been undertaken to enlist the possible target sites for quercetin to boost the wound healing process along with application of artificial intelligence (AI)-based techniques for the development of stable, cost-effective and patient-friendly topical drug delivery systems for better management of DFU in future

Computational and experimental therapeutic efficacy analysis of andrographolide phospholipid complex self-assembled nanoparticles against Neuro2a cells

Background: Neuroblastoma is one of the most common malignancies in childhood, accounts for approximately 7% of all malignancies. Andrographolide (AN) inhibits cancer cells progression via multiple pathways like cell cycle arrest, mitochondrial apoptosis, NF-κβ inhibition, and antiangiogenesis mechanism. Despite multiple advantages, application of AN is very limited due to its low aqueous solubility (6.39 ±0.47 μg/mL), high lipophilicity (log P ~ 2.632 ±0.135), and reduced stability owing to pH sensitive lactone ring. Objectives and results: In present investigation, a molecular complex of AN with soya-L-α-phosphatidyl choline (SPC) was synthesized as ANSPC and characterized by FT-IR and1H NMR spectroscopy. Spectral and molecular simulation techniques confirmed the intermolecular interactions between the 14-OH group of AN and the N+(CH3)3 part of SPC. In addition, molecular dynamics (MD) simulation was used to determine the degree of interaction between various proteins such as TNF-α, caspase-3, and Bcl-2. Later, ANSPC complex was transformed in to self-assembled soft nanoparticles of size 201.8 ±1.48 nm with PDI of 0.092 ± 0.004 and zeta potential of 21.7 ± 0.85 mV. The IC50 of free AN (8.319 μg/mL) and the self-assembled soft ANSPC nano-particles (3.406 μg/mL ~ 1.2 μg of AN) against Neuro2a cells was estimated with significant (P <0.05) difference. Interestingly, the self-assembled soft ANSPC nanoparticles showed better endocytosis compared to free AN in Neuro2a cells. In vitro biological assays confirmed that self-assembled soft ANSPC nanoparticles induces apoptosis in Neuro2a cells by declining the MMP (Δψm) and increasing the ROS generation. Conclusion: Self-assembled soft ANSPC nanoparticles warrant further in-depth antitumor study in xenograft model of neuroblastoma to establish the anticancer potential