This study was focussed on development of curcumin loaded solid binary lipid nanoparticles (C-SBLNs) to ameliorate stability, uptake and therapeutic potential of curcumin during inflammatory bowel disease (IBD). C-SBLNs with nano-size range (210.56 ± 41.22 nm) and high entrapment efficiency (83.12 ± 6.57%) were prepared by solvent emulsification evaporation method using binary lipids i.e. stearic acid and tristearin after optimizing various formulation and process variables. Physicochemical characterization of C-SBLNs by ATR-FTIR confirmed drug entrapment whereas thermal and pXRD study corroborated loss of crystallinity of drug into C-SBLNs. Lyophilized C-SBLNs were found to be spherical shaped with good gastrointestinal stability and prolonged drug release up to 24 h. Optimized C-SBLNs formulation displayed significantly enhanced cellular uptake and localization in inflamed tissues during IBD. Oral administration of C-SBLNs in DSS induced colitis model revealed significant reduction in leucocyte infiltration, oxidative stress, pro-inflammatory cytokine (TNF-α) secretion and maintenance of colonic structure similar to healthy animal group compared to curcumin. Thus, in vitro and preclinical findings of study clearly confirmed that C-SBLNs could be a stable and efficacious alternative platform for curcumin delivery with strong competence in IBD chemotherapy. Graphical Abstract

The major obstacles for treatment of intracellular infections with clarithromycin are poor gastrointestinal solubility, short half-life (3–4 h), low oral bioavailability and hepatotoxicity. Therefore, clarithromycin loaded solid lipid nanocarriers (CLA-SLNs) were engineered by an emulsification solvent evaporation method to improve CLA in vivo pharmacokinetics and safety. Various formulation variables such as type of surfactant, concentration of surfactant, binary lipid ratio, continuous phase volume and sonication time were optimized considering particle size and entrapment efficiency as quality parameters. The optimized CLA-SLN formulation exhibited a maximum entrapment efficiency of 84 ± 9% and smallest particle size of 307 ± 23 nm with a zeta potential of −29 mV. Physicochemical characterization of CLA-SLNs by differential scanning calorimetry and powder X-ray diffraction confirmed entrapment of CLA and its phase transformation from crystalline to amorphous in the SLN formulation. Morphological characterization revealed a smooth and spherical shape of the optimized CLA-SLNs which prolonged the controlled diffusion of the drug upto 24 h. In vitro antibiofilm activity disclosed the higher potential of CLA-SLNs in biofilm eradication at lower drug concentration (40 μg ml⁻¹) compared to free CLA (140 μg ml⁻¹), which was confirmed by SEM images. A pharmacokinetic study in wistar rats depicted higher C_max (2.3-fold), T_max (2-fold), MRT (1.4-fold) and almost 5-fold improvement in relative oral bioavailability of CLA on oral administration of CLA-SLNs. Furthermore, cytotoxicity studies in macrophage cell line and repeated oral dose toxicity study confirmed the safety of the CLA-SLN formulation. In conclusion, CLA-SLNs can serve as a superior carrier system with high oral bioavailability of CLA and can improve the therapeutic potential of CLA in treatment of intracellular infections.

Atorvastatin, a favored option for hyperlipidemia exhibits the problem of poor gastric solubility and low absolute bioavailability (12%) along with higher pre-systemic clearance (>80%). Therefore, to circumvent these limitations, atorvastatin nanocrystals were prepared using poloxamer-188 as stabilizer via high pressure homogenization technique followed by lyophilization. Various variables like drug to poloxamer-188 ratio, homogenization cycle, homogenization pressure, type and concentration of cryoprotectant were optimized to achieve uniform nanosized crystals with good dispersibility. Solid state characterization by ATR-FTIR and DSC revealed no incompatible physicochemical interaction between drug and excipients in formulation while DSC and PXRD collectively corroborated the reduced crystallinity of drug in nanocrystals. Size analysis and SEM confirmed nanometric size range of nanocrystals (225.43 ± 24.36 nm). Substantial improvement in gastric solubility (~40 folds) and dissolution rate of drug in nanocrystals was observed. Pharmacokinetic study in wistar rats revealed significant improvement in oral bioavailability (~2.66 folds) with atorvastatin nanocrystals compared to pure drug. Furthermore, reduction in serum total lipid cholesterol, LDL and triglyceride content justified the effectiveness of formulation at 50% less dose of atorvastatin along with improved plasma safety profile in comparison of pure drug. In conclusion, atorvastatin nanocrystals are safe and efficacious drug delivery system confirming potent competence in treatment of hyperlipidemic conditions with ease of scalability for commercialization.

The objective of the present investigation was to develop an enteric nano-formulation of bromelain to improve its stability and anti-inflammatory potential. Bromelain loaded nanoparticles (Br-NPs) were developed using a Eudragit L 100 polymer by a double emulsion solvent evaporation method to obtain gastro-resistant properties. Br-NPs were characterized for particle size (248.89 ± 22.76 nm), zeta potential (−27.34 ± 2.17 mV), entrapment efficiency (85.42 ± 5.34%), surface morphology (spherical) and in vitro release profile. Infrared spectroscopy confirmed the entrapment of bromelain while thermal and pXRD analysis concomitantly corroborated the reduced crystallinity of bromelain in nanoparticles. Formulations showed gastro-resistant behavior at gastric pH and sustained bromelain release up to 10 h in phosphate buffer at pH 6.8 and followed Higuchi square root release kinetics. The optimized lyophilized formulation ensured 2 year shelf-life at room temperature. In vivo studies revealed significantly improved performance of entrapped bromelain in inhibiting carrageenan induced paw edema by mitigating leucocyte migration and release of nitric oxide, TNFα and IL-1β in paw compared to bromelain solution. In conclusion, enteric Br-NPs could be a viable drug delivery system for effective oral bromelain delivery in inflammatory conditions.

Attempts have been made to optimize immobilization parameters, catalytic property, and stability of immobilized α-amylase in agar. The work compares natural entrapment efficiency of agar with the ionotropically cross-linked agar hydrogel, with the advantage of easy scale-up and cost and time effectiveness. Beads prepared with 3% (w/v) agar and 75 mM calcium chloride and hardened for 20 minutes were selected for further studies on the basis of entrapment efficiency (80%) and physical stability. Following entrapment, pH and temperature optima of enzyme were shifted from 6 to 6.5 and 50 to 55°C, respectively. Michaelis constant (Km) for both free and entrapped enzymes remained the same (0.83%) suggesting no change in substrate affinity. However, Vmax⁡ of entrapped enzyme decreased ~37.5-fold. The midpoint of thermal inactivation for entrapped enzyme increased by 8 ± 1°C implying its higher thermal stability. The entrapped enzyme in calcium agar bead had an E_a value of 27.49 kcal/mol compared to 17.6 kcal/mol for free enzyme indicating increased stability on entrapment. Half-life of enzyme increased ~2.2 times after entrapment in calcium agar at 60°C indicating stabilization of enzyme. The reusability of beads was size dependent. Beads with diameter <710 μm were stable and could be reused for 6 cycles with ~22% loss in activity.