A standardized protocol was used to compare cellular toxicities and anti-human immunodeficiency virus type 1 (HIV-1) activities of candidate microbicides formulated for human use. The microbicides evaluated were cellulose acetate phthalate (CAP), Carraguard, K-Y plus nonoxynol-9 (KY-N9), PRO 2000 (0.5 and 4%), SPL7013 (5%), UC781 (0.1 and 1%), and Vena Gel, along with their accompanying placebos. Products were evaluated for toxicity on cervical and colorectal epithelial cell lines, peripheral blood mononuclear cells (PBMCs), and macrophages (MΦ) by using an ATP release assay, and they were tested for their effect on transepithelial resistance (TER) of polarized epithelial monolayers. Anti-HIV-1 activity was evaluated in assays for transfer of infectious HIV-1 from epithelial cells to activated PBMCs and for PBMC and MΦ infection. CAP, Carraguard, PRO 2000, SPL7013, and UC781 along with their placebos were 20- to 50-fold less toxic than KY-N9 and Vena Gel. None of the nontoxic product concentrations disrupted the TER. Transfer of HIV-1Ba-L from epithelial cells to PBMCs and PBMC and MΦ infection with laboratory-adapted HIV-1Ba-L and HIV-1LAI isolates were inhibited by all products except Carraguard, KY-N9, and Vena Gel. KY-N9, Vena Gel, and Carraguard were not effective in blocking PBMC infection with primary HIV-1A, HIV-1C, and HIV-1CRF01-AE isolates. The concordance of these toxicity results with those previously reported indicates that our protocol may be useful for predicting toxicity in vivo. Moreover, our systematic anti-HIV-1 testing provides a rational basis for making better informed decisions about which products to consider for clinical trials

Recent studies indicate that mucosal innate immune factors modulate HIV-1 infection in vitro. Our interest was to examine the levels of innate mucosal factors for their potential association with HIV-1 shedding in the female genital tract. Vaginal lavages were collected from HIV-1-infected women who had vaginal viral loads (VVL) that were below, within, or above the 90% confidence interval (CI) predicted by their matched plasma viral loads. Innate immune factors [cathepsin D, lactoferrin (Lf), myeloid related protein (MRP)-8, MRP-8/14, secretory leukocyte protease inhibitor, and gp340], cytokines (IL-1beta and TNF-alpha), and chemokines (MIP-1alpha, MIP-1beta, RANTES, and SDF-1alpha) were quantified by ELISA. Leukocyte levels were determined using a leukocyte reagent strip for urinalysis. Lf, MRP-8/14, gp340, and IL-1beta levels were significantly higher in vaginal lavages above the 90% CI and generally correlated with each other and with VVL. Leukocyte levels were significantly higher in the lavages that had virus shedding above the 90% CI and correlated strongly with Lf levels and VVL. In this group of women, these results suggest that the levels of certain innate immune factors are more closely associated with HIV-1 shedding in the genital mucosa than plasma virus concentrations.

The purpose of this study was to evaluate the possibility of lectin-coupled microspheres to improve the targeted delivery of protein antigens to the lymphoid tissues of mucosal surfaces. Bovine serum albumin containing acid phosphatase model protein and polystyrene microspheres were coupled with mouse M-cell-specific Ulex europaeus lectin. The coupling efficiency, physical characteristics and the binding capabilities of the microspheres to the follicle associated epithelium of the Peyer's patches were evaluated in vitro and ex vivo in mice intestine. The results showed that coupling of lectin to albumin microspheres did not significantly affect the bioactivity of the encapsulated acid phosphatase model protein. It was also shown that there was preferential binding of the lectin-coupled microspheres to the follicle-associated epithelium. It was concluded from the results of the study that coupling of ligands such as lectin specific to cells of the follicle associated epithelium can increase the targeting of encapsulated candidate antigens for delivery to the Peyer's patches of the intestine for improved oral delivery.

Most ocular surgical procedures take approximately 60 min to complete, the anaesthetic property of the safest drug, tetracaine, is initiated in a few minutes and lasts approximately 10-15 min. The purpose of the present study was to develop an ocular tetracaine formulation which can produce an immediate onset of action and/or longer duration of action during the entire surgical procedure. Tetracaine-loaded microparticle formulation was prepared by the method of spray-drying and characterized in terms of size, zeta potential, morphology, thermal stability and release pattern. The study reports a microparticulate ocular formulation with minimum cytotoxicity and optimum cellular uptake. In addition, microencapsulated tetracaine was found to significantly increase the duration of action of the drug up to 4-fold. Taken together, the results presented in this work described albumin-chitosan microparticles to be an effective delivery platform for ocular anaesthetic agents and a potential treatment of various ocular diseases.

Catalase in albumin microspheres were formulated for intravenous administration to antagonize the effects of over-production of reactive oxygenated species (ROS) such as hydrogen peroxide (H(2)O(2)) in septic shock. The aim was to increase effective half-life of catalase and take advantage of the phagocytic uptake of the encapsulated catalase by the vascular endothelium. Catalase microspheres were prepared by spray-drying. The microspheres were evaluated for particle size, particle shape and surface morphology by scanning electron microscopy (SEM), drug encapsulation efficiency, chemical stability, thermal stability and in vitro drug release characteristics. The microspheres had a mean particle size of 4.7 +/- 2 microm, optimal for phagocytic uptake, as demonstrated by Makino et al. SEM revealed that microspheres were spherical with smooth surface morphology. An encapsulation efficiency of 91.5 +/- 3% was achieved and the encapsulated catalase was chemically and thermally stable. Application of in vitro drug release data to the Higuchi kinetic equation indicated matrix diffusion-controlled catalase release from albumin microspheres.

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It can be concluded from the study that the lectin-coupled microspheres had better affinity for M-cells and showed preferential binding to the Peyer's patches. This means that the coupling enhanced the targeted delivery of the antigens to the M cells.

Cannabis consumer products are a $4.6 billion industry in the U.S. that is projected to exceed $14 billion by 2025. Despite an absence of U.S. Food and Drug Administration (FDA) regulation or clinical data, thousands of nutraceuticals, topical consumer products, and beauty products claim benefits of hemp or cannabidiol. However, a lack of required quality control measures prevents consumers from knowing the true concentration or purities of cannabis-labeled products. Thirteen over-the-counter consumer products were examined for the presence of cannabidiol (CBD), cannabinol (CBN), Δ9-tetrahydrocannabinol (THC), cannabidiolic acid (CBDA), and Δ9-tetrahydrocannabinolic acid A (THCA). Additionally, the efficacy of topical applications was investigated using a porcine skin model, in which particle size and zeta potential relate to skin permeability. Skin permeation was correlated to particle size and relative stability in skin-like conditions but not directly related to the CBD content, suggesting that topical products can be designed to enhance overall skin permeation. Of the products analyzed, all products have some traceable amount of cannabinoids, while seven products had multiple cannabinoids with quantifiable amounts. Overall, the need for further regulation is clear, as most products have apparent distinctions between their true and labeled contents.