Making nanoscale drug carriers could boost the bioavailability of medications that are slightly water soluble. One of the most promising approaches for enhancing the chemical stability and bioavailability of a variety of therapeutic medicines is liquid nanocrystal technology. This study aimed to prepare nanocrystals of mangiferin for sustained drug delivery and enhance the pharmacokinetic profile of the drug. The fractional factorial design (FFD) was used via a selection of independent and dependent variables. The selected factors were the concentration of mangiferin (A), hydroxypropyl methyl cellulose (HPMC) (B), pluronic acid (C), tween 80 (D), and the ratio of antisolvent to solvent (E). The selected responses were the particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The nanocrystals were further evaluated for mangiferin release, release kinetics, Fourier transforms infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), particle size, zeta potential, and scanning electron microscopy (SEM). The stability studies of developed nanocrystals were performed for 6 months and pharmacokinetics on albino rabbits. The value of entrapment efficiencies ranged from 23.98% to 86.23%. The percentage release of mangiferin varied from 62.45 to 99.02%. FTIR and DSC studies showed the stability of mangiferin in the nanocrystals. The particle size of the optimized formulation was almost 100 nm and −12 mV the value of the zeta potential. The results of stability studies showed that the nanocrystals of mangiferin were stable for a period of six months. The peak plasma concentration of mangiferin from nanocrystals and suspension of mangiferin were 412 and 367 ng/mL, respectively. The value of AUC_0−t of nanocrystals and suspension of mangiferin was 23,567.45 ± 10.876 and 18,976.12 ± 9.765 µg×h/mL, respectively, indicating that the nanocrystals of mangiferin showed greater availability of mangiferin compared to the suspension of the formulation. The developed nanocrystals showed a good release pattern of mangiferin, better stability studies, and enhanced the pharmacokinetics of the drug.

Gemcitabine (GC)-loaded chitosan nanoparticles were synthesized by ionic gelation method, and optimization was accomplished by Box–Behnken design based on particle size (PS), polydispersity index (PDI), zeta potential (ZP), and percent entrapment efficiency (% EE). The optimized formulation (OF) exhibited PS, PDI, ZP, and % EE to be 206.7 nm, 0.285, +27 mV, and 77.61%, respectively. Fourier transform infrared spectroscopy, X-ray diffraction analysis, and differential scanning calorimetry analyses confirmed GC’s stability in nanoparticles. The OF showed an initial rapid release of 61%, followed by a slower release, reaching 95.81% over 96 h. OF was studied on a PC-3 cell line to evaluate its effectiveness in treating prostate cancer, where it exhibited higher cytotoxicity (IC ₅₀ ∼3.06 ± 0.32 μg/ml) compared to pure GC (IC ₅₀ ∼4.11 ± 0.81 μg/ml). After oral administration in albino rabbits, the peak plasma concentrations ( C _max ) for GC solution and OF were 1,290 and 3,070 ng/ml, respectively. The time to reach maximum plasma concentration ( t _max ) was 1 h for GC solution and 6 h for OF. The half-life ( t _1/2 ) was 5.6 h for GC solution and 16.9 h for OF, indicating a prolonged half-life for OF. OF demonstrated an effective release pattern of GC, improved stability, enhanced pharmacokinetic profile, and higher toxicity compared to GC.