Peer Papers

**Methotrexate-loaded polymeric lipid hybrid nanoparticles (PLHNPs): a reliable drug delivery system for the treatment of glioblastoma

Polymeric lipid hybrid nanoparticles (PHLNPs) are core-shell nanoparticle structures made up of polymer cores and lipid shells that have properties similar to both polymeric nanoparticles and liposomes. Methotrexate (MTX) loaded PLHNPs containing tween 80, phosphatidylcholine, poly D, L-lactic-co-glycolic acid (PLGA) and glyceryl tripalmitate prepared using solvent injection and homogenisation method for a glioblastoma treatment option. The MTX-loaded PLHNPs optimised by Box–Behnken design to minimise particle size, higher entrapment efficacy and maximise MTX concentration in the brain at 4 h. The particle size, entrapment efficacy, concentration of drug in the brain at 4 h, zeta potential, and AUC(Brain)/AUC(Plasma) ratio were in the range of 173.51–233.37 nm, 70.56–86.34%, 6.38–12.38 μg/mL, 25.78–36.31 mV and 1.02–5.32. In-vitro drug release studies, cellular internalisation of optimised formulation against U-87 MG shows good anticancer effects.

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**Statistically designed vitamin D3 Encapsulated PLGA **microspheres dispersed in thermoresponsive in-situ gel for nasal delivery

Vitamin D deficiency is a cause of concern across the world. It is a fat-soluble vitamin and exhibits two molecular forms (D2 and D3). The aim of the present study is the development and optimization of vitamin D3 loaded PLGA microspheres by using Box Behnken Design. Additionally, to enhance nasal permeation these microspheres were dispersed in the thermoreversible in-situ gel. Microspheres revealed particle size in the range of 9182 ± 1 nm with 75.5 ± 0.5%EE of vitamin D3. Polydispersity index and zeta potential of microspheres were found 0.509 and −7.56 mV, respectively confirming uniformity and colloidal stability. FTIR and DSC studies revealed no interaction between excipients and vitamin D3. Scanning electron microscopy demonstrated spherical morphology of microspheres. The thermoreversible in-situ dispersed with vitamin D3 loaded microspheres exhibit the gelation temperature between 35 °C to 37 °C. The viscosity of the gel was 35698–5032 cps. The gel strength was found 1.1 ± 0.2 mJ with hardness (27 g), adhesiveness (22 g), and stringiness (3.2 mm) measured by a texture analyzer. In vitro dissolution study revealed that microspheres showed 79% VD3 release. Whereas microspheres dispersed gel showed 69% of VD3 release up to one week as compared to an oily solution.

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