Enhanced permeability and photoprotective potential of optimized p-coumaric acid-phospholipid complex loaded gel against UVA mediated oxidative stress.

Photo-oxidative skin damage is mainly caused by the UV-A radiation of the sun. Synthetic sunscreens used to counter this acts mostly on the superficial skin layer and possess serious side effects. P-coumaric acid (PCA) is a UV-A protective plant phenolic having quick diffusion and distribution in superficial skin layers limiting its application as herbal sunscreen. The present study was designed to formulate an optimized phospholipid complex of PCA (PCAPC) through response surface methodology to enhance its skin permeation to deeper skin layers providing protection against photo-oxidative stress. PCAPC was characterized by FT-IR, DTA, PXRD, TEM, zeta potential etc. PCAPC was then incorporated into a gel formulation (PCAPC-GE) to facilitate its transdermal delivery. Physicochemical properties of the gel were assessed by pH, homogeneity, rheology, spreadability etc. In-vitro SPF and UVA-PF of the gel was evaluated and compared with conventional gel (PCA-GE). Ex-vivo skin permeation flux, permeability coefficient, skin deposition and dermatokinetic analysis were carried out to measure the rate and level of skin permeation. This was accompanied by in-vivo evaluation of PCAPC-GE and PCA-GE in the experimental rat model by measuring the various oxidative stress markers such as superoxide dismutase, catalase etc. PCAPC-GE provided high SPF and UVA-PF value compared to PCA-GE. The physicochemical parameters were suitable for transdermal application. PCAPC-GE enhanced the permeation rate of PCA by almost 6 fold compared to PCA-GE. Besides, a significant reduction of UV-A induced oxidative stress biomarkers were observed for PCAPC-GE. Thus, the PCAPC-GE may be an effective alternative of synthetic sunscreens due to its enhanced permeation and protection against UVA-induced oxidative stress.

Optimized piperine-phospholipid complex with enhanced bioavailability and hepatoprotective activity.

Piper species is one of the most widely consumed spices for culinary purposes. Piperine (PIP) present in Piper species has a wide range of therapeutic activity including hepatoprotection. However, the major biological limitation of PIP is its low bioavailability after oral administration. Purpose of the study was to prepare an optimized and adequately characterized PIP-phospholipid complex (PPC) as a delivery system to overcome these limitations and to investigate the pharmacokinetics and hepato-protectivity of the formulation in the animal model. Response surface methodology was adopted to optimize the process parameters for PPC preparation. FT-IR, DTA, PXRD, SEM, molecular docking etc. were used for characterization. Solubility, log P, dissolution efficiency and in vivo pharmacokinetics were also investigated. PPC showed enhanced hepatoprotective potential as compared to pure PIP at the same dose level (25 and 50 mg/kg). PPC restored the levels of serum marker and antioxidant enzymes. PPC also increased the bioavailability of PIP in rat serum by 10.40-fold in comparison with pure PIP at the same dose level and enhanced the elimination half-life (t1/2 el) from 0.477 ± 1.76 to 9.80 ± 1.98 h. Results concluded that PPC enhanced the hepatoprotection of PIP which may be due to the improved bioavailability and pharmacokinetics of PIP in rats.

Enhanced bioavailability and hepatoprotectivity of optimized ursolic acid-phospholipid complex.

OBJECTIVE: To prepare and characterize an optimized phospholipid complex of Ursolic acid (UA) to overcome the poor pharmacokinetic properties and to investigate the impact of the complex on hepatoprotective activity and bioavailability in animal model. SIGNIFICANCE: UA is a potential phytoconstituent obtained from several plant sources, which has been explored for its diverse pharmacological activities including hepatoprotection. Its major limitation is poor absorption, rapid elimination, and hence low bioavailability after administration. METHODS: Response surface methodology was adopted to formulate an optimized (UA) complex. The complex was characterized by differential thermal analysis (DTA), Fourier transform-Infrared Spectroscopy, Powder X ray Diffraction, molecular docking, etc. The physico-chemical profile (solubility, oil/water partition coefficient) and in vitro dissolution profile was estimated. The formulation was then used to study hepatoprotective activity and bioavailability in animal models. RESULTS: Results showed that the phospholipid complex of UA has enhanced the hepatoprotective potential as compared to pure UA at the same dose level. The complex restored the levels of serum hepatic marker enzymes with respect to untreated group and increased the relative bioavailability of UA in rat plasma by 8.49-fold in comparison with pure compound at the same dose level. It enhanced the elimination half-life (t1/2 el) from 0.69 ± 1.76 to 8.28 ± 1.98 h. CONCLUSION: Complexation of UA with phospholipid markedly enhanced the hepatoprotective potential of UA by improving its bioavailability and pharmacokinetic parameters. Novelty statement The present article deals with rational optimization of the formulation parameters for phospholipid complex of ursolic acid by Response Surface Methodology analysis, characterizing the formulation by in silico approach apart from conventional instrumental techniques, and evaluating the in vitro dissolution, pharmacokinetics, and hepatoprotective activity of the complex in animals. Novelty statement The present article deals with rational optimization of the formulation parameters for phospholipid complex of ursolic acid by Response Surface Methodology analysis, characterizing the formulation by in silico approach apart from conventional instrumental techniques, and evaluating the in vitro dissolution, pharmacokinetics, and hepatoprotective activity of the complex in animals.