Nanocrytals-Mediated Oral Drug Delivery: Enhanced Bioavailability of Amiodarone.

The aim of this study was to improve the saturation solubility, dissolution profile and oral bioavailability of amiodarone hydrochloride (AMH), a highly lipophilic drug. Stabilizer (Pluronic F-127)-coated AMH nanocrystals (AMH-NCs) were developed by a combination of antisolvent precipitation and homogenization techniques. The optimized formulation comprised pluronic F-127 and AMH at the concentration of 4% and 2% w/v, respectively. The particle size (PS), zeta potential (ZP) and polydispersity index (PDI) of the optimized formulation was found to be 221 ± 1.2 nm, 35.3 mV and 0.333, respectively. The optimized formulation exhibited a rough surface morphology with particles in colloidal dimensions and a significant reduction in crystallinity of the drug. AMH-NCs showed a marked increase in the saturation solubility as well as rapid dissolution rate when compared with the AMH and marketed product. The stability study displayed that the formulation was stable for 3 months, with no significant change in the PS, ZP and PDI. The in vivo pharmacokinetic study demonstrated the ability of AMH-NCs to significantly (p < 0.05) improve the oral bioavailability (2.1-fold) of AMH in comparison with AMH solution, indicating that the production of AMH-NCs using a combination of antisolvent precipitation and homogenization techniques could enhance the bioavailability of the drug.

Surface modified multifaceted nanocarriers for oral non-conventional cancer therapy; synthesis and evaluation.

Inflammatory cells orchestrate tumor niche for the proliferating neoplastic cells, leading to neoangiogenesis, lymphangiogenesis, tumor growth and metastasis. Emergence of severe side effects, multiple drug resistance and associated high cost has rendered conventional chemotherapy less effectual. The aim was to develop a multipurpose, less toxic, more potent and cheaper, oral non-conventional anticancer therapeutic. Cyclooxygenase associated with tumor niche inflammation and proliferative neoplastic cells were targeted synergistically, through anti-inflammatory and anti-proliferative effects of model drug, diclofenac sodium and fluorescent silver nanoparticles (AgNPs), respectively. Drug entrapped AgNPs were surface modified with PVA (for controlling particle size, preferred cellular uptake, evading opsonization and improved dispersion). XRD, FTIR, DSC, TGA, LIBS, particle size and surface plasmon resonance analysis confirmed the efficient drug encapsulation and PVA coating with 62% loading efficiency. In-vitro, the formulation exhibited 1st order release kinetics with sustained and maximal release at slightly acidic conditions (pH 4.5) enabling the potential for passive tumor targeting. Also, nanoparticles showed efficient protein denaturation inhibition potential, hemo-compatibility (<0.8%) and potent anti-cancer activity (P < 0.05) against breast cancer cell line (MCF-7). In-vivo, developed nanoparticles improved pharmacokinetics (2.8 fold increased AUC, 6.9 h t1/2, Cmax = 1.6 ±â€¯0.03 µg/ml, Kel = 0.1) and pharmacodynamics manifested by potent anti-inflammatory, analgesic and anti-pyretic effects (P < 0.05) at 20 fold lower doses. LD50 determination revealed a wide therapeutic window. The study showed promise of synthesized nanomaterials as cheaper, less toxic, hemo-compatible, oral and more potent anti-inflammatory and non-conventional fluorescent anti-cancer agents, vanquishing tumor niche inflammation and repressing proliferation of malignant cells.

Development and Evaluation of Optimized Thiolated Chitosan Proniosomal Gel Containing Duloxetine for Intranasal Delivery.

Proniosomes offer excellent potential for improved drug delivery, through versatile routes, by overcoming the permeation barriers faced by several drugs. The study was aimed to develop a thiomer gel containing duloxetine proniosomes for the intranasal delivery, improving its bioavailability and brain delivery through olfactory system. Duloxetine-loaded proniosomes were optimized through Design-Expert Software, prepared by coacervation phase separation method and then characterized in vitro for different vesicle features, and permeation enhancement potential using various techniques. The formulation F2, out of all the trials, fulfilled the maximum requisite of highest entrapment efficiency (76.21 ± 1.24%) and minimum vesicle size (223.91 ± 11.07 nm). The F2 was embedded in thiolated chitosan gel rendering it mucoadhesive and further characterized. The in vitro release showed a sustained drug release from the mucoadhesive proniosomal gel with only 54% drug release as compared to that of 71% from proniosome over 8 h, following Higuchi drug release model. Ex vivo permeation studies showed the enhancement ratio for the mucoadhesive proniosomal gel to be 1.86-fold greater than proniosomes, indicating a significant improvement in transmucosal permeation. The results suggest that incorporation of proniosomes into thiolated gel can significantly improve its mucoadhesion and retention time in the nasal cavity for providing a sustained drug release. Thus, gel formulation could be considered as a promising approach for efficient intranasal drug delivery of duloxetine. Graphical Abstract.