Investigating the effectiveness of Difluprednate-Loaded core-shell lipid-polymeric hybrid nanoparticles for ocular delivery.

Uveitis is a sight-threatening disease that causes inflammation in the uvea; difluprednate (DFB) is the first approved drug molecule for postoperative pain, inflammation, and endogenous uveitis. Complex ocular physiology and structure make it difficult to deliver drugs to the eye. Increased permeation and retention in the layer of the eye are required to improve the bioavailability of ocular drugs. In the current research investigation, DFB-loaded lipid polymer hybrid nanoparticles (LPHNPs) were designed and fabricated to enhance the corneal permeation and sustained release of DFB. A well-established two-step approach was used to fabricate the DFB-LPHNPs, comprising of Poly-Lactic-co-Glycolic Acid (PLGA) core that entrapped the DFB and DFB loaded PLGA NPs covered by lipid shell. The manufacturing parameters were optimized for the preparation of DFB-LPHNPs; the optimal DFB-LPHNPs showed a mean particle size of 117.3 ± 2.9 nm, suitable for ocular administration and high entrapment efficiency of 92.45 ± 2.17 % with neutral pH (7.18 ± 0.02) and isotonic Osmolality (301 ± 3 mOsm/kg). Microscopic examination confirms the core-shell morphological structure of DFB-LPHNPs. The prepared DFB-LPHNPs were extensively characterized using spectroscopic techniques and physicochemical characterization, which confirms the entrapment of the drug and the formation of the DFB-LPHNPs. The confocal laser scanning microscopy studies revealed that Rhodamine B-loaded LPHNPs were penetrated into stromal layers of the cornea in ex-vivo conditions. The DFB-LPHNPs showed a sustained release pattern in simulated tear fluid and 4- folds enhanced permeation of DFB as compared to pure DFB solution. The ex-vivo histopathological studies revealed that DFB-LPHNPs didn't cause any damage or no alteration in the cellular structure of the cornea. Additionally, the results of the HET-CAM assay confirmed that the DFB-LPHNPs were not toxic for ophthalmic administration.

Perspective insights of small molecules, phytoconstituents and biologics in the management of psoriasis: A focus on targeting major inflammatory cytokine pathways.

Psoriasis is an enduring, pruritic and papulosquamous skin ailment that poses a significant burden on public health. It is mainly characterized by hyperkeratosis, acanthosis, parakeratosis, scaly and erythematous plaques. Biomarkers like interleukin-17, interleukin-12 and -23 and tumor necrosis factor-α serve as key drivers of psoriatic pathogenesis. Triggered release of pro-inflammatory cytokines from various up-regulated pathways leads to psoriatic inflammation. Several target moieties like biologics, small molecules and herbal moieties play a fundamental role in the repression of pathogenesis of psoriasis. Biologics and small molecules engaged in the management of psoriasis have been emphasized in detail. An insight into nano-carrier interventions on herbal moieties and clinical aspects of psoriasis are also highlighted. This review emphasizes various pathological targets involved in psoriasis.