Design of Nanosystems for the Delivery of Quorum Sensing Inhibitors: A Preliminary Study

Biofilm production is regulated by the Quorum Sensing system. Nowadays, Quorum Sensing represents an appealing target to design new compounds to increase antibiotics effects and avoid development of antibiotics multiresistance. In this research the use of liposomes to target two novel synthetic biofilm inhibitors is presented, focusing on a preformulation study to select a liposome composition for in vitro test. Five different liposome (LP) formulations, composed of phosphatidyl choline, cholesterol and charged surfactant (2:1:1, molar ratio) have been prepared by direct hydration and extrusion. As charged surfactants dicetyl phosphate didecyldimethylammonium chloride, di isobutyl phenoxy ethyl dimethyl benzyl ammonium chloride and stearylamine (SA) and have been used. Liposome charge, size and morphology were investigated by zeta potential, photon correlation spectroscopy, small angle x-ray spectroscopy and electron microscopy. LP-SA was selected for the loading of biofilm inhibitors and subjected to high performance liquid chromatography for entrapment capacity evaluation. LP-SA loaded inhibitors showed a higher diameter (223.6 nm) as compared to unloaded ones (205.7 nm) and a dose-dependent anti-biofilm effect mainly after 48 h of treatment, while free biofilm inhibitors loose activity. In conclusion, our data supported the use of liposomes as a strategy to enhance biofilm inhibitors effect.

In VitroandIn VivoEvaluation of Niosomal Formulation for Controlled Delivery of Clarithromycin

The present study was focused on formulating and evaluating clarithromycin (CLR) containing niosomal formulation forin vitroandin vivopharmacokinetic behavior. Niosomal formulations (empty and drug loaded) were prepared by using different ratio of surfactant (various Span grades 20, 40, 60, and 80) and cholesterol by thin film hydration method and were evaluated forin vitrocharacteristics, stability studies, andin vivostudy. Dicetyl phosphate (DCP) was added to the niosomal formulation. Various pharmacokinetic parameters were determined from plasma of male SD rats. Span 60 containing niosomal formulation NC2(cholesterol to surfactant ratio 1 : 1) displayed highest entrapment efficiency with desired particle size of 4.67 μm. TEM analyses showed that niosomal formulation was spherical in shape. Niosomes containing Span 60 displayed higher percentage of drug release after 24 h as compared to other formulations. NC2formulation was found to be stable at the end of the study on storage condition. Various pharmacokinetic parameters, namely, AUC, AUMC, and MRT of niosomal formulation, were found to be 1.5-fold, 4-fold, and 3-fold plain drug, respectively. The present study suggested that niosomal formulations provide sustained and prolonged delivery of drug with enhance bioavailability.

Formulation and Evaluation of Guggul Lipid Nanovesicles for Transdermal Delivery of Aceclofenac

Context. Most new drugs have low water solubility and liposome is an important formulation to administer such drugs; however, it is quite unstable and has negligible systemic absorption.Objective. Aceclofenac nanovesicles were made using guggul lipid for formulating stable transdermal formulation.Materials and Methods. Guggul lipid was formulated into vesicles along with cholesterol and dicetyl phosphate using film hydration method. The formulations were analyzed for physicochemical properties and stability. Then its skin permeation and anti-inflammatory activity were determined.Results. Both categories of vesicles (PC and GL) showed optimum physicochemical properties; however, accelerated stability study showed considerable differences. GL-1 was appreciably stable for over 6 months at 4°C. Corresponding gels (PCG-1 and GLG-1) showedCmaxvalues at 4.98 and 7.32 μg/mL along with theTmaxvalues at 4 and 8 hours, respectively. GLG-1 inhibited edema production by 90.81% in 6 hours.Discussion. PC liposomes are unstable at higher temperature and upon longer storage. The formulation with higher lipid content (GL-1) showed good drug retention after 24 hours and appreciable stability both at higher temperature and for longer duration. Guggul lipid being a planar molecule might be stacked in vesicle wall with cholesterol.Conclusion. The composition of the nanovesicle played an important role in stability and drug permeation. Guggul lipid is suitable for producing stable vesicles.

Formulation and Characterization of Drug Loaded Nonionic Surfactant Vesicles (Niosomes) for Oral Bioavailability Enhancement

Nonionic surfactant vesicles (niosomes) were formulated with an aim of enhancing the oral bioavailability of tenofovir disoproxil fumarate (TDF), an anti-HIV drug. Niosomes were formulated by conventional thin film hydration technique with different molar ratios of surfactant, cholesterol, and dicetyl phosphate. The formulated niosomes were found spherical in shape, ranging from 2.95 μm to 10.91 μm in size. Vesicles with 1 : 1 : 0.1 ratios of surfactant : cholesterol : dicetyl phosphate with each grade of span were found to have higher entrapment efficiencies, which were further selected forin vitroandin vivostudies. Vesicles formulated with sorbitan monostearate were found to have maximum drug release (99.091%) at the end of 24 hours and followed zero order release kinetics. The results ofin vivostudy revealed that the niosomes significantly enhanced the oral bioavailability of TDF in rats after a dose of 95 mg/kg. The average relative bioavailability of niosomes in relation to plane drug solution was found to be 2.58, indicating more than twofold increase in oral bioavailability of TDF. Significant increase in mean residential time (MRT) was also found, reflecting release retarding efficacy of the vesicles. In conclusion, niosomes could be a promising delivery for TDF with improved oral bioavailability and prolonged release profiles.

INFLUENCE OF BIOENHANCERS ON THE RELEASE PATTERN OF NIOSOMES CONTAINING METHOTREXATE

The aim of present study was to prepare sustained release formulations of niosomes of methotrexate (MTX) alone (N1 to N10) and along withbioenhancers (NB1 to NB9) by thin film hydration technique using span 60 as surfactant,cholesterol as membrane stabilizing agent, curcumin and piperine as bioenhancers and dicetyl phosphate (DCP) as charge inducing agent. All the formulations of niosomeswere characterized on the basis of physical appearance and entrapment efficiency. The invitro releasestudies of optimized formulation of niosomes of MTX alone and along with bioenhancers were performed and compared with pure drug released. The entrapment efficiency of MTX in optimized formulation of niosomes containing MTX along with bioenhancers was found to 56.9% and entrapment efficiency of bioenhancerscurcumin and piperinewas found to be 40.30% and 69.1%respectively. In vitro drug release of optimized formulationsof niosomes of MTX without and with bioenhancers (F3) was found to be 98.89% and 60.97% at the end of 12 h respectively. Results concluded that Niosomes of MTX containing bioenhancers followed sustain release pattern.

ENHANCEMENT OF FOLLICULAR DELIVERY OF FINASTERIDE IN NIOSOMALAND PRONIOSOMAL GEL FORM FOR TREATING ANDROGENETIC ALOPECIA

Finasteride has not been explored extensively for the treatment of androgenic alopecia. The present workwas aimed to enhance the follicular delivery of finasteride topically by niosomal and proniosomal carriersystems for treating androgenetic alopecia. Finasteride niosomes were prepared by thin film hydrationmethod and proniosomes were prepared by coacervation phase separation method. The niosomesprepared with cholesterol-Span 20 (1:1) and proniosmes prepared with cholesterol-Span 20 (1:1) showedbetter mean vesicle size, drug content, in vitro release profile and skin permeability. The effect of chargeinducer, dicetyl phosphate (DCP) on skin permeability of niosomes and proniosomes was studied and itwas found to be less in this study. Stability studies were preformed and the formulation was found to bestable for 60 days. Clinical trials by phototrichogram method was performed for proniosomal formulationwith cholesterol-Span 20 (1:1) and DCP on twenty healthy male volunteers and it was found to increasethe anagen hair count of test group by 42.85 % when compared with the control group (6.6%), indicatingthe proniosomal gel formulation achieved the objective of enhancing the drug concentration in androgenicreceptors of hair shaft and thus it can be used safely for treating androgenic alopecia.