Formulation and optimization of theophylline-loaded enteric-coated spanlastic nanovesicles for colon delivery; Ameliorate acetic acid-induced ulcerative colitis.

Treatment of colon diseases presents one of the most significant obstacles to drug delivery due to the inability to deliver sufficient drug concentration selectively to the colon. The goal of the proposed study was to develop, optimize, and assess an effective colon target delivery system of theophylline-based nanovesicles (TP-NVs) surrounded by a biodegradable polymeric shell of chitosan (CS) and Eudragit L100 (EL100) for the treatment of ulcerative colitis (UC). TP-loaded nanovesicles were fabricated using the ethanol injection method and coated with CS and EL100, respectively. We used a 32-factorial design approach to optimize the concentration of CS and EL100 to minimize particle size (PS) and maximize the cumulative amount of theophylline released (CTR) after 24 h. The optimized formulation was described using transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and in vitro release. In-vivo quantification of theophylline in the gastrointestinal tract and in-vivo targeting potential in a rat model of acetic acid-induced colitis were also thoroughly evaluated. The characteristics of the optimal formula predicted by the 32-factorial design approach corresponded exceptionally well with the measured PS of 271.3 nm, the zeta potential of -39.9 mV, and CTR of 3.95, and a 99.93% after 5 and 24 h, respectively. Notably, the in vivo results in the rat model of colitis showed that the formulation with an optimized coat significantly improved theophylline distribution to the colon and markedly decreased the expression of interleukin-6 and ulcerative lesions compared to a pure theophylline solution. These outcomes elucidated the feasibility of a 32-factorial design to detect the crucial interactions between the study's components. Our findings suggested that enteric-coated nanovesicles formulations with optimal coat compositions of 0.2693% (w/v) and 0.75% (w/v) of CS and EL100, respectively, were promising carriers for colonic delivery of theophylline, a rate-limiting step in the treatment of UC.

EthoLeciplex: a new tool for effective cutaneous delivery of minoxidil.

This work designates EthoLeciplex, a vesicular system consisting of phospholipid, CTAB, ethanol and water, as an innovative vesicular system for cutaneous/transfollicular minoxidil (MX) delivery. MX-loaded EthoLeciplex was fabricated by one-step fabrication process. Formulations were designed to study the effects of drug/phospholipid ratio, CTAB/phospholipid ratio, and ethanol concentration on vesicular size, PDI, surface charge and EE%. The optimized formulation was characterized by in vitro release, drug/excipient compatibility, ex vivo skin permeability and safety. A size of 83.6 ± 7.3 to 530.3 ± 29.4 nm, PDI of 0.214 ± 0.01 to 0.542 ± 0.08 and zeta potential of +31.6 ± 4.8 to +57.4 ± 12.5 mV were observed. Encapsulation efficiency was obtained in its maximum value (91.9 ± 16.2%) at the lowest drug/phospholipid ratio, median CTAB/phospholipid and the highest ethanol concentration. The optimized formulation was consisted of 0.3 as drug/lipid ratio, 1.25 as CTAB/lipid ratio and 30% ethanol concentration and showed responses' values in agreement with the predicted results. Differential scanning calorimetry studies suggested that EthoLeciplex existed in flexible state with complete incorporation of MX into lipid bilayer. The cumulative amount of MX permeated from EthoLeciplex, conventional liposome and ethanolic solution after 12 h were 36.3 ± 1.5 µg/ml, 21 ± 2.0 µg/ml and 55 ± 4.0 µg/ml respectively. Based on the remaining amount, the amount of MX accumulated in different skin layers can be predicted in descending order as follows; EthoLeciplex > conventional liposome > MX solution. EthoLeciplex produced marked disorder in the stratum corneum integrity and swelling with no features of skin toxicity. This new cationic system is a promising carrier for cutaneous/transfollicular drug delivery.

Impact of highly phospholipid-containing lipid nanocarriers on oral bioavailability and pharmacodynamics performance of genistein.

Oxidative stress is a leading cause of different diseases. Genistein is a valuable bioflavonoid possessing antioxidant and anti-inflammatory activity but unfortunately, it suffers from low aqueous solubility, extremely poor bioavailability and first pass effect when used in its pure state. The aim of this work was to formulate and characterize genistein-loaded highly phospholipid-containing lipid nanocarriers to improve oral bioavailability and pharmacodynamic performance. Lipid nanocarriers were prepared by the emulsification/sonication technique. The influence of phospholipid percentage (1%-10%) on physicochemical properties, drug release and stability was investigated. The particle size, zeta potential and EE% were in ranges from 211.9 ± 21.6 to 342.3 ± 7.9 nm, -11.6 ± 1.7 to -19.4 ± 3.1 mV and 78.5 ± 4.7% to 92.2 ± 1.9%, respectively. Drug release was less predominant in the case of SLN formulations when compared to corresponding NLC formulations. High phospholipid percentage produced less stable formulations in terms of particle size growth, gelation and heterogeneous particle distributions. DSC, FT-IR and XRD tools revealed that genistein has existed in an amorphous form in NLC4. The bioavailability of NLC4 was approximately 2.6-fold greater than that of conventional suspension. Additionally, lipid peroxidation in liver homogenate and histopathological alterations in liver and kidney sections were particularly improved, providing a promising strategy for oral administration of genistein.