Investigation of dimyristoyl phosphatidyl glycerol and cholesterol based nanocochleates as a potential oral delivery carrier for methotrexate.

Methotrexate (MTX), a biopharmaceutical classification system-IV anticancer drug, exhibits low therapeutic efficacy. Moreover, its clinical applications were restricted due to its multidrug resistance (MDR) in cancer and its toxic effects. The present investigation was to fabricate 1, 2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium (DMPG-Na), (3ß)-cholest-5-en-3-ol (cholesterol) and calcium-based nanocochleates (NCs) as a potential oral delivery carrier for MTX to enhance its therapeutic efficacy with low toxicity. MTX-loaded NCs (MTX-NCs) was developed by the addition of calcium ion into preformed nanoliposomes (MTX-NLs) comprising MTX, DMPG-Na, with cholesterol and evaluated by in-vitro and in-vivo methods in comparison with MTX-NLs and pure MTX. Stable tubular rod structure of MTX-NCs possessing particle size, encapsulation efficiency and zeta potential of 374.1 ± 2.2 nm, 78.63 ± 2.12% and -71.2 mV, respectively were obtained from homogenous unilamellar, discrete and spherical structured MTX-NLs with a diameter and zeta potential of 363.3 ± 3.7 nm and -74.6 mV respectively. A thermal study revealed an amorphous state of MTX in MTX-NCs. Pharmacokinetics study in rats, MTX-NLs and MTX-NCs were showed controlled release with 5 and 6 fold improvements in oral bioavailability. Moreover, MTX-NCs showed low tissue distribution. These results collectively suggest that the developed system could be used to improve the therapeutic efficacy of MTX.

Investigation of 1,2-Dimyristoyl-sn-Glycero-3-Phosphoglycerol-Sodium (DMPG-Na) Lipid with Various Metal Cations in Nanocochleate Preformulation: Application for Andrographolide Oral Delivery in Cancer Therapy.

This study aimed at carrying out a preformulation investigation of nanocochleates (NCs) and develop andrographolide-loaded nanocochleates. Preformulation study comprised of exploring the effect of trivalent and divalent ions on transition temperature (TT) of lipid (DMPG-Na), on particle size (PS), entrapment efficacy (EE), zeta potential (ZP) of NCs, and effect of NCs on change in lipid solubility post-NC formation. Further, the andrographolide-loaded nanocochleates made with CaCl2 (ANDNCs) were characterized for ZP, PS, EE, X-ray powder diffraction (PXRD), differential scanning calorimetry (DSC), transition electron microscopy (TEM), in vitro release studies, in vitro anticancer potential on the cell line of human breast cancer (MCF-7), in vivo oral pharmacokinetic studies, and tissue distribution in female Wistar rats. Nanocochleates developed with CaCl2 had a significant reduction in PS (1.78-fold) and ZP (1.38-fold), and elevation of EE (1.17-fold) as compared to AlCl3 developed NCs. Trivalent ions demonstrated elevation of TT as compared to divalent ions. Spiral-shaped ANDNCs demonstrated ZP, PS, and EE of - 121.46 ± 15.12 mV, 360 ± 47 nm, and 68.12 ± 3.81% respectively. In vitro release study of ANDNCs showed a strong pH-dependent release profile due to hydrogen bonding between NCs and andrographolide (AND). Formulated ANDNCs demonstrated 26.99-fold decrease in IC50 value as compared to free AND. Additionally, the oral bioavailability of AND from ANDNCs improved by 1.81-fold as compared to free AND. Furthermore, ANDNCs showed minimum accumulation within the vital organs such as liver, kidney, and spleen. Briefly, the preformulation study laid a platform for better understanding the NCs and its components. Further, developed ANDNCs revealed superior physiochemical properties to be used as an alternative for a clinical setting.

Current development in novel drug delivery systems of bioactive molecule plumbagin.

Plumbagin (PLB), a member of the quinine family, mainly found in the plant Plumbago zeylanica Linn., potentially exhibit anticancer, anti-inflammatory, anti-oxidant, antifungal, neuroprotective, hypolipidemic and antibacterial activities. However, it has been well known that the application of PLB was limited owing to its water insolubility, instability and poor bioavailability. For decades, many attempts have been made to compensate for these disadvantages with the development of improved delivery platforms as the feasible approaches. This review aims to describe the various studies supporting the biopharmaceutical aspects of PLB. In addition, it includes a section devoted to discussing the challenges associated with the drug and strategies to improve the properties of PLB such as solubility, stability and bioavailability. Also, this paper summarizes the recent works on the design and development of novel delivery systems of PLB such as liposomes, niosomes, microsphares, nanoparticles, micelles, complexization, metal nanoparticles, crystals modification, etc., with the goal of harnessing the true difficulties of this multifunctional agent in the clinical arena.

Improved bioavailability of orally administered andrographolide from pH-sensitive nanoparticles.

Andrographolide, a major bioactive phytoconstituent derived from Androgaphis paniculata that is safe and beneficial in several ailments, was formulated into pH-sensitive nanoparticle suspension with a view of improving its oral bioavailability. The andrographolide-loaded pH-sensitive nanoparticles were prepared by nanoprecipitation technique using Eudragit® EPO (cationic poly methacrylate copolymer). The 3(2) factorial design was used to optimize the amount of polymer and stabilizer (Pluronic® F-68). The optimized batch obtained using 0.45% w/v of Eudragit® EPO and 0.6% w/v of Pluronic® F-68 showed high-encapsulation efficiency of 93.8±0.67% with particle size of 255±9 nm and zeta potential of 29.3±3.4 mV. The bioavailability of andrographolide from optimized nanoparticles and pure andrographolide was assessed in male Wistar albino rats at a dose of 10 mg/kg. As compared to the pure andrographolide, almost 2.2 and 3.2-fold increase in AUC0-∞, Cmax and 121.53% increase in relative bioavailability were observed for andrographolide from pH-sensitive nanoparticles (P<0.05). Shorter Tmax by about fourfold difference were observed with 2.2-fold decrease in Cl/F. The improved dissolution rate owing to its reduced particle size, increased surface area and reduced diffusion layer thickness may have contributed to oral bioavailability. The results clearly indicate the potential of pH-sensitive nanoparticles for oral delivery of low-bioavailability phytoconstituents such as andrographolide.

Studies on nonionic surfactant bilayer vesicles of ciclopirox olamine.

CONTEXT: Niosomal delivery can prove an alternative to improve the poor skin penetration and residence of the topical antifungal drugs that account for the long treatment regimes in cutaneous mycosis. OBJECTIVE: To investigate niosomes as carriers for dermal delivery of ciclopirox olamine (CPO), a broad spectrum antifungal drug. MATERIALS AND METHODS: Niosomes were prepared by ethanol injection method using Span 60, cholesterol, diacetyl phosphate according to 3(2) factorial design and evaluated for physicochemical parameters, in vitro and ex vivo deposition in skin and stability study. RESULTS: Unilamellar CPO niosomes of size 170-280 nm, entrapment efficiency 38-68%, and sufficient electrokinetic stability were obtained. Percent drug deposition in artificial membrane varied from 12.75 to 92.74. Deposition of CPO into rat skin from niosomal dispersion and its gel was significantly higher than that of plain CPO solution and its marketed product. Obtained niosomes possessed sufficient stability on storage. DISCUSSION: Increasing amounts of Span 60 and cholesterol increase the vesicle size probably because of entrapment of CPO-ionized molecules in the aqueous compartment and interaction of its unionized counterpart with the bilayer constituents leading to increase in bilayer thickness. Consequently, the percent entrapment efficiency also increased. However, increasing Span 60 levels decreased the in vitro percent drug deposition. This might be attributed to the larger size of vesicles produced by high amounts of surfactant that showed poor deposition. The optimized batch possessed sufficient stability. CONCLUSIONS: The results of this investigation suggest that niosomes are promising tools for cutaneous retention of CPO.