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Objective: The study aimed at designing a pH sensitive Lipid polymeric Hybrid nanoparticle (LPHNP) for targeted release of Paclitaxel (PTX) and Curcumin (CUR) in breast cancer., Significance: Such systems shall result in controlled triggered release in acidic microenvironment of tumor cells with improved pharmacokinetic profile., Methods: Chitosan-coated CUR and PTX coloaded pH-sensitive LPHNPs were synthesized employing nanoprecipitation technique. The synthesized NPs were characterized in terms of particle size, polydispersity index (PDI), zeta potential, and morphology., Results: LPHNPs co-loaded with curcumin (CUR) and paclitaxel (PTX) were successfully formulated, achieving a size of 146 nm, a PDI of 0.18, and an entrapment efficiency exceeding 90%. In vitro release studies demonstrated controlled release of CUR and PTX under tumor pH conditions showing 1.6 fold and 1.7 fold higher release in ABS pH 5 in comparison to PBS 7.4 for PTX and CUR respectively. MTT-assay studies revealed enhanced cytotoxicity of CUR and PTX as LPHNPs showing IC 50 value of free CUR & PTX 480.06 µg/mL decreasing to 282.97 µg/mL for CS-CUR-PTX-LPHNPs. In vivo pharmacokinetic evaluations in rats confirmed significantly improved bioavailability, with a 3.8-fold increase in AUC for CUR and a 6.6-fold increase for PTX. Additionally, the LPHNPs demonstrated controlled release and prolonged retention, evidenced by a 2.2-fold increase in the half-life (t1/2) of CUR and a 1.3-fold increase in the half-life of PTX., The results underscores potential of chitosan-coated LPHNP as a promising delivery platform, offering high drug loading, optimal size for cellular penetration, and prolonged blood circulation for cancer.

The purpose of this study was to develop a nanosuspension of a poorly soluble drug felodipine by nanoprecipitation to achieve superior in vitro dissolution and high oral absorption in vivo in rats. Felodipine nanosuspensions were prepared by precipitation with ultrasonication method using polyvinyl alcohol (PVA) and hydroxy propyl methyl cellulose (HPMC) as stabilizers. The particle size of nanosuspension with PVA was 60-200 nm, while with HPMC is 300-410 nm. The in vitro dissolution and pharmacokinetics of optimized nanosuspensions were studied after oral administration in male wistar rats. The results showed significant improvement during in vitro dissolution and in vivo plasma level. Dissolution studies of lyophillised nanoparticles showed that up to 93.0 % dissolved in 2 h. In the in vivo evaluation, nanosuspension exhibited significant increase in AUC0-24, C max and decrease in t max. The findings revealed that particle size reduction can influence felodipine absorption in gastrointestinal tract and nanosuspension can enhance oral bioavailability of felodipine in rats.

Furosemide is a weakly acidic diuretic indicated for treatment of edema and hypertension. It has very poor solubility but high permeability through stomach and upper gastrointestinal tract (GIT). Due to its limited solubility it has poor and variable oral bioavailibility of 10-90%. The aim of this study was to enhance the oral bioavailibilty of furosemide by preparation of nanosuspensions. The nanosuspensions were prepared by nanoprecipitation with sonication using DMSO (dimethyl sulfoxide) as a solvent and water as an antisolvent (NA). The prepared nanosuspensions were sterically stabilized with polyvinyl acetate (PVA). These were characterized for particle size, zeta potential, polydispersity index, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) pattern and release behavior. The average particle size of furosemide nanoparticles were found to be in the range of 150-300 nm. This was further confirmed by SEM photograph. The particle size varies with an increase in concentration of drug and stabilizer. The preparations showed negative zeta potential and polydispersity index in the range of 0.3 +/- 0.1. DSC and XRD studies indicated that the crystalline furosemide drug was converted to amorphous form upon precipitation into nanoparticles. The saturation solubility of prepared furosemide nanoparticles markedly increased compared to the original drug in simulated gastric fluid. The release profiles of nanosuspension formulation showed up to 81.2% release in 4 h. It may be concluded that the nanoprecipitation with ultrasonication have potential to formulate homogenous nanosuspensions with uniform sized amorphous nanoparticles of furosemide. Polyvinyl acetate can be used as a suitable steric stabilizer to prepare stable furosemide nanosuspensions. The enhanced saturation solubility in simulated gastric fluid may lead to enhanced absorption of furosemide.