Development, Characterization and Comparative Phar-macokinetic Evaluation of Ritonavir Nanosuspension, with a Model Nanoemulsion and Coarse Suspension for Improved Oral Delivery

Ritonavir (RV) is an antiretroviral drug, classified as BCS class II pharmaceutical active.It has limited bioavailability due to poor aqueous solubility and first pass metabolism. The purpose of this investigation was to develop optimal nanosuspension and to compare with a model nanoemulsion of RV for improved oral delivery. DSC studies showed good compatibility of excipients with drug. Nanosuspension was prepared by high pressure homogenization, while nanoemulsion was prepared by hot homogenization followed by ultrasonication. All prepared RV formulations were characterized and optimal system was selected and in vivo evaluated. Nanosuspension (F1) formulation containing 0.5% SLS showed homogeneity with least particle size was optimized and compared with coarse (powder) suspension. SEM studies on lyophilized nanosuspension revealed the absence of needle shaped drug crystals, indicating the loss of crystallinity. Prepared a model lipid nanoemulsion. It was having the size, PDI, ZP, EE and assay of 193.14 ± 12.66nm, 0.311 ± 0.04, -27.6 ± 1.184mV, 90.79 ± 0.319% and 99.57 ± 1.25% respectively. Next, a comparative pharmacokinetic study of RV nanosuspenison with respect to lipid nanoemulsion and coarse suspension was performed in male wistar rats. The Cmax of nanosuspension was significantly more when compared to that of NE or coarse drug suspension. The tmax was similar in case of both nanodelivery systems and significantly less when compared to that of coarse suspension. About 1.36 and 1.27 fold improvements in relative bioavailability (BA) of ritonavir via lipid nanoemulsion and nanosuspension were found when compared to coarse suspension. The study results revealed nominal but nonsignificant difference in oral bioavailability for the two nanodelivery systems. Taken together, this study confirmed the potential of nanosuspension and nanoemulsion systems in improving the bioavailability of ritonavir.

Syngonanthus nitens (Bong.) Ruhland Derivatives Loaded into a Lipid Nanoemulsion for Enhanced Antifungal Activity Against Candida parapsilosis

Background: Vaginal infections caused by non-albicans species have become common in women of all age groups. The resistance of species such as Candida parapsilosis to the various antifungal agents is a risk factor attributed to these types of infections, which instigates the search for new sources of active compounds in vulvovaginal candidiasis (VCC) therapy. Objective: This study evaluated the antifungal activity of Syngonanthus nitens Bong. (Ruhland) derivatives and employed a lipid nanoemulsion as a delivery system. Methods: In this study, a lipid nanoemulsion was employed as a delivery system composed of Cholesterol (10%), soybean phosphatidylcholine: Brij 58 (1: 2) and PBS (pH 7.4) with the addition of 0.5% of a chitosan dispersion (80%), and evaluated the antifungal activity of S. nitens Bong. (Ruhland) derivatives against planktonic cells and biofilms of Candida parapsilosis. By a biomonitoring fractionation, the crude extract (EXT) and one fraction (F2) were selected and incorporated into a lipid nanoemulsion (NL) composed of cholesterol (10%), a 1:2 mixture of soybean phosphatidylcholine:polyoxyethylene -20- cetyl ether (10%), and phosphate buffer solution (pH 7.4) with a 0.5% chitosan dispersion (80%). The NL presented a diameter size between 50-200 nm, pseudoplastic behavior, and positive charge. The EXT and five fractions were active against planktonic cells. Results and Discussion: The incorporation of EXT and F2 into the NL increased antifungal activity and enhanced the anti-biofilm potential. This study classified the use of an NL as an important tool for the administration of S. nitens derivatives in cases of infections caused by this C. parapsisilosis. Conclusion: This work concluded that S. nitens derivatives were important sources of active molecules against C. parapsilosis and the use of a lipid nanoemulsion was an important tool to promote more effective F2 release and to improve the antifungal activity aiming the control of C. parapsilosis infections.

Elicitation of Novel Trichogenic-Lipid Nanoemulsion Signaling Resistance Against Pearl Millet Downy Mildew Disease

Nanoemulsion was formulated from membrane lipids of Trichoderma spp. with the non-ionic surfactant Tween 80 by the ultrasonic emulsification method. Nanoemulsion with a droplet diameter of 5 to 51 nm was obtained. The possible effects of membrane lipid nanoemulsion on pearl millet (PM) seed growth parameters and elicitation of downy mildew (DM) disease resistance in PM was analyzed to develop an eco-friendly disease management strategy. Seed priming with nanoemulsion illustrates significant protection and elevated levels of early defense gene expression. Lipid profiling of Trichoderma spp. reveals the presence of oleic acid as a major fatty acid molecule. The prominent molecule in the purified lipid fraction of T. brevicompactum (UP-91) responsible for the elicitation of induction of systemic resistance in PM host against DM pathogen was predicted as (E)-N-(1, 3-dihydroxyoctadec-4-en-2yl) acetamide. The results suggest that protection offered by the novel nanoemulsion formulation is systemic in nature and durable and offers a newer sustainable approach to manage biotrophic oomycetous pathogen.

Lipid nanoemulsion passive tumor accumulation dependence on tumor stage and anatomical location: a new mathematical model for in vivo imaging biodistribution studies

Nanoparticle delivery to tumor tissue is one of the most important applications of nanomedicine.

Nanotherapy for Alzheimer's disease and vascular dementia: Targeting senile endothelium

Due to the complexity of Alzheimer's disease, multiple cellular types need to be targeted simultaneously in order for a given therapy to demonstrate any major effectiveness. Ultrasound-sensitive coated microbubbles (in a targeted lipid nanoemulsion) are available. Versatile small molecule drug(s) targeting multiple pathways of Alzheimer's disease pathogenesis are known. By incorporating such drug(s) into the targeted LCM/ND lipid nanoemulsion type, one obtains a multitasking combination therapeutic for translational medicine. This multitasking therapeutic targets cell-surface scavenger receptors (mainly SR-BI), making possible for various Alzheimer's-related cell types to be simultaneously searched out for localized drug treatment in vivo. Besides targeting cell-surface SR-BI, the proposed LCM/ND-nanoemulsion combination therapeutic(s) include a characteristic lipid-coated microbubble [LCM] subpopulation (i.e., a stable LCM suspension); such film-stabilized microbubbles are well known to substantially reduce the acoustic power levels needed for accomplishing temporary noninvasive (transcranial) ultrasound treatment, or sonoporation, if additionally desired for the Alzheimer's patient.

Alzheimer's Disease, Brain Injury, and C.N.S. Nanotherapy in Humans: Sonoporation Augmenting Drug Targeting

Owing to the complexity of neurodegenerative diseases, multiple cellular types need to be targeted simultaneously in order for a given therapy to demonstrate any major effectiveness. Ultrasound-sensitive coated microbubbles (in a targeted nanoemulsion) are available. Versatile small-molecule drug(s) targeting multiple pathways of Alzheimer's disease pathogenesis are known. By incorporating such drug(s) into the targeted LCM/ND lipid nanoemulsion type, one obtains a multitasking combination therapeutic for translational medicine. This multitasking therapeutic targets cell-surface scavenger receptors (mainly SR-BI), making possible for various Alzheimer's-related cell types to be simultaneously searched out for localized drug treatment in vivo. Besides targeting cell-surface SR-BI, the proposed LCM/ND-nanoemulsion combination therapeutic(s) include a characteristic lipid-coated microbubble [LCM] subpopulation (i.e., a stable LCM suspension); such LCM substantially reduce the acoustic power levels needed for accomplishing temporary noninvasive (transcranial) ultrasound treatment, or sonoporation, if additionally desired for the Alzheimer's patient.

Nanotherapy for Early Dementia: Targeting Senile Endothelium

Due to the complexity of Alzheimer's disease, multiple cellular types need to be targeted simultaneously in order for a given therapy to demonstrate any major effectiveness. Ultrasound-sensitive coated microbubbles (in a targeted lipid nanoemulsion) are available. Versatile small molecule drug(s) targeting multiple pathways of Alzheimer's disease pathogenesis are known. By incorporating such drug(s) into the targeted LCM/ND lipid nanoemulsion type, one obtains a multitasking combination therapeutic for translational medicine. This multitasking therapeutic targets cell-surface scavenger receptors (mainly SR-BI), making possible for various Alzheimer's-related cell types to be simultaneously searched out for localized drug treatment in vivo. Besides targeting cell-surface SR-BI, the proposed LCM/ND-nanoemulsion combination therapeutic(s) include a characteristic lipid-coated microbubble [LCM] subpopulation (i.e., a stable LCM suspension); such film-stabilized microbubbles are well known to substantially reduce the acoustic power levels needed for accomplishing temporary noninvasive (transcranial) ultrasound treatment, or sonoporation, if additionally desired for the Alzheimer's patient.