Because lubricants may decrease trauma during coitus, it is hypothesized that they could aid in the prevention of HIV acquisition. Therefore, safety and anti-HIV-1 activity of over-the-counter (OTC) aqueous- (n = 10), lipid- (n = 2), and silicone-based (n = 2) products were tested. The rheological properties of the lipid-based lubricants precluded testing with the exception of explant safety testing. Six aqueous-based gels were hyperosmolar, two were nearly iso-osmolar, and two were hypo-osmolar. Evaluation of the panel of products showed Gynol II (a spermicidal gel containing 2% nonoxynol-9), KY Jelly, and Replens were toxic to Lactobacillus. Two nearly iso-osmolar aqueous- and both silicone-based gels were not toxic toward epithelial cell lines or ectocervical or colorectal explant tissues. Hyperosmolar lubricants demonstrated reduction of tissue viability and epithelial fracture/sloughing while the nearly iso-osmolar and silicon-based lubricants showed no significant changes in tissue viability or epithelial modifications. While most of the lubricants had no measurable anti-HIV-1 activity, three lubricants which retained cell viability did demonstrate modest anti-HIV-1 activity in vitro. To determine if this would result in protection of mucosal tissue or conversely determine if the epithelial damage associated with the hyperosmolar lubricants increased HIV-1 infection ex vivo, ectocervical tissue was exposed to selected lubricants and then challenged with HIV-1. None of the lubricants that had a moderate to high therapeutic index protected the mucosal tissue. These results show hyperosmolar lubricant gels were associated with cellular toxicity and epithelial damage while showing no anti-viral activity. The two iso-osmolar lubricants, Good Clean Love and PRÉ, and both silicone-based lubricants, Female Condom 2 lubricant and Wet Platinum, were the safest in our testing algorithm.
Use of lubricant products is extremely common during receptive anal intercourse (RAI) yet has not been assessed as a risk for acquisition of sexually transmitted infections (STIs).
From 2006–2008 a rectal health and behavior study was conducted in Baltimore and Los Angeles as part of the UCLA Microbicide Development Program (NIAID IPCP# #0606414). Participants completed questionnaires and rectal swabs were tested for Neisseria gonorrhoeae and Chlamydia trachomatis with the Aptima Combo 2 assay and blood was tested for syphilis (for RPR and TPHA with titer) and HIV. Of those reporting lubricant use and RAI, STI results were available for 380 participants. Univariate and multivariate regressions assessed associations of lubricant use in the past month during RAI with prevalent STIs.
Consistent lubricant use during RAI in the past month was reported by 36% (137/380) of participants. Consistent past month lubricant users had a higher prevalence of STI than inconsistent users (9.5% vs. 2.9%; p=0.006). In a multivariable logistic regression model testing positive for STI was associated with consistent use of lubricant during RAI in the past month (adjusted Odds Ratio (AOR) 2.98 (95%CI 1.09, 8.15) after controlling for age, gender, study location, HIV status, and numbers of RAI partners in the past month.
Findings suggest some lubricant products may increase vulnerability to STIs. Because of wide use of lubricants and their potential as carrier vehicles for microbicides, further research is essential to clarify if lubricant use poses a public health risk.
rectal sexually transmitted infections; lubricants; rectal health
Previous research on the use of personal lubricants for sexual intercourse is limited and has primarily focused on condom compatibility and breakage, with only recent limited assessment of lubricant safety and possible epidemiologic implications. This article discusses the global evidence of lubricant compatibility with latex condoms and biological safety of lubricants, as well as documentation of lubricant use and current guidelines for HIV prevention programming in Africa. Data on lubricant compatibility with condoms are less available than commonly realized, and many lubricant products may not have been thoroughly tested for safety due to flexible regulatory environments. Recent laboratory and study findings from microbicides research also suggest that some water-based lubricants may have safety issues. Some African populations are using several types of lubricants, especially oil-based petroleum jellies, and receive little evidence-based guidance. More research is needed from the medical community to guide prevention programming.
lubricants; condoms; HIV prevention; Africa
Over-the-counter vaginal lubricants have been shown to negatively affect in vitro sperm motility. The objective of this study was to estimate the effect of vaginal lubricant use during procreative intercourse on natural fertility.
Women aged 30–44 years with no history of infertility who had been trying to conceive for less than 3 months completed a baseline questionnaire on vaginal lubricant use. Subsequently, women kept a diary to record menstrual bleeding, intercourse, and vaginal lubricant use and conducted standardized pregnancy testing for up to 6 months. Diary data were used to determine the fertile window and delineate lubricant use during the fertile window. A proportional hazards model was used to estimate fecundability ratios with any lubricant use in the fertile window considered as a time-varying exposure.
Of the 296 participants, 75 (25%) stated in their baseline questionnaire that they use vaginal lubricants while attempting to conceive. Based on daily diary data, 57% of women never used a lubricant, 29% occasionally used a lubricant, and 14% used a lubricant frequently. Women who used lubricants during the fertile window had similar fecundability to those women who did not use lubricants (fecundability ratio 1.05, 95% CI: 0.59, 1.85) after adjusting for age, partner race, and intercourse frequency in the fertile window.
Lubricants are commonly used by couples during procreative intercourse. Lubricant use during procreative intercourse does not appear to reduce the probability of conceiving.
This study assessed the acceptability and preference for sexual barrier and lubricant products among men in Zambia following trial and long-term use. It also examined the role of men's preferences as facilitators or impediments to product use for HIV transmission reduction within the Zambian context. HIV-seropositive and - serodiscordant couples were recruited from HIV voluntary counseling and testing centers in Lusaka between 2003 and 2006; 66% of those approached agreed to participate. HIV seropositive male participants participated in a product exposure group intervention (n = 155). Participants were provided with male and female condoms and vaginal lubricants (Astroglide® [BioFilm, Inc., Vista, CA] & KY® gels [Johnson & Johnson, Langhorne, PA], Lubrin® suppositories [Kendwood Therapuetics, Fairfield, NJ]) over three sessions; assessments were conducted at baseline, monthly over 6 months and at 12 months. At baseline, the majority of men reported no previous exposure to lubricant products or female condoms and high (79%) levels of consistent male condom use in the last 7 days. Female condom use increased during the intervention, and male condom use increased at 6 months and was maintained over 12 months. The basis for decisions regarding lubricant use following product exposure was most influenced by a preference for communicating with partners; participant preference for lubricant products was distributed between all three products. Results illustrate the importance of development of a variety of products for prevention of HIV transmission and of inclusion of male partners in interventions to increase sexual barrier product use to facilitate barrier acceptability and use in Zambia.
The results of the CAPRISA 004 and iPrEx HIV prevention studies have demonstrated that topical or systemic use of antiretroviral agents can significantly reduce the risk of HIV acquisition associated with unprotected vaginal or anal sexual intercourse. However, the effect size in these studies was relatively modest and product adherence was generally poor. These observations suggest the need for new approaches to HIV prevention, especially for high risk MSM. Rates of lubricant use are high in MSM practicing receptive anal sex. Consequently, the development of an antiretroviral rectal microbicide gel may provide a safe and effective means of preventing HIV infection with an intervention that is likely to have high acceptability among the target population. The purpose of this article is to describe the challenges and progress in the development of rectal microbicides for HIV prevention.
HIV; Microbicides; Rectal; HIV prevention
Thin-layer chromatography has been used to identify phospholipids extracted from canine synovial fluid, the major component (45%) being phosphatidyl choline (PC). The extracts and their components have been shown to be surface active in reducing the surface tension of water and to be readily adsorbed to hydrophilic solids, whose surfaces then become hydrophobic. These adsorbed monolayers of synovial surfactant were then found to be excellent boundary lubricants in vitro, reducing the coefficient of kinetic friction (mu) in the dry state and under physiological loading by up to 97% for extracts and 99% for PC alone, reaching mu = 0.01. Surface-active phospholipid is put forward as the possible active ingredient in joint lubrication and shown to be consistent with previous biochemical studies to elucidate its identity. The model essentially follows the classical Hardy model for boundary lubrication imparted by surfactants. It is discussed in relation to a new approach in providing artificial lubrication and facilitating tissue release in patients with arthritis.
This paper explores the exposure and impact of a Scottish mass media campaign: Make Your Position Clear. It ran from October 2009 to July 2010, targeted gay men and other men who have sex with men (MSM), and had two key aims: to promote regular sexual health and HIV testing every 6 months, and to promote the use of appropriate condoms and water-based lubricant with each episode of anal intercourse.
A cross-sectional survey (anonymous and self-report) was conducted 10 months after the campaign was launched (July 2010). Men were recruited from commercial venues. Outcome measures included use of lubricant, testing for sexually transmitted infections and HIV, and intentions to seek HIV testing within the following six months. Linear-by-linear chi-square analysis and binary logistic regressions were conducted to explore the associations between the outcome measures and campaign exposure.
The total sample was 822 men (62.6% response rate). Men self-identifying as HIV positive were excluded from the analysis (n = 38). Binary logistic analysis indicated that those with mid or high campaign exposure were more likely to have been tested for HIV in the previous six months when adjusted for age, area of residence and use of the “gay scene” (AOR = 1.96, 95% CI = 1.26 to 3.06, p = .003), but were not more likely to be tested for STIs (AOR = 1.37, 95% CI = 0.88 to 2.16, p = .167). When adjusted for previous HIV testing, those with mid or high campaign exposure were not more likely to indicate intention to be tested for HIV in the following six months (AOR = 1.30, 95% CI = 0.73 to 2.32, p = .367). Those with no campaign exposure were less likely than those with low exposure to have used appropriate lubricant with anal sex partners in the previous year (AOR = 0.42, 95% CI = 0.23 to 0.77, p = .005).
The campaign had demonstrable reach. The analysis showed partial support for the role of mass media campaigns in improving sexual health outcomes. This suggests that a role for mass media campaigns remains within combination HIV prevention.
Gay men; Mass media; Sexual health; HIV test; Exposure
Objectives: Anal cytology smears are either collected "blind" (swab inserted 4 cm into anal canal and rotated) or guided through an anoscope (transformation zone visualised and then sampled). We compared these smear techniques with respect to sample quality and patient acceptability.
Methods: Using a paired, random sequence clinical trial, 151 homosexual men (n = 95 HIV positive) underwent both smear techniques at a single visit; smear order was randomised and specimens were read blind. Both techniques utilised a Dacron swab, with water lubrication. Cytological specimens were prepared using a liquid based collection method (ThinPrep). The outcome measures were cytological specimen adequacy, cytological classification, presence of rectal columnar, squamous and metaplastic cells, contamination, patient comfort and acceptability, and volume of fluid that remained after the ThinPrep procedure.
Results: Regardless of smear order, guided smears were less likely to detect higher grade abnormalities than blind smears (15 v 27 cases, p = 0.001). Controlling for smear order, guided smears were more likely to be assessed as "unsatisfactory" for cytological assessment (OR 6.93, 95% CI 1.92 to 24.94), and contain fewer squamous (OR 0.20, 95% CI 0.04 to 0.94) and metaplastic cells (OR 0.12, 95% CI 0.03 to 0.54) than blind smears; there were no other statistically significant differences between techniques. Regardless of smear technique, first performed smears were more likely to detect a higher grade abnormality than second performed smears (23 v eight cases, p<0.001).
Conclusions: Blind cytology smears are superior to anoscope guided smears for screening for anal neoplasia in homosexual men.
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.
Water can be used as an ecological lubricant base if it is possible to select additives which can beneficially modify its tribological and corrosion properties. Additionally, those additives should not be harmful to human health and the natural environment. These conditions limit or even eliminate the possibility for the application of the additives used in traditional oil bases as they are insoluble in water and often toxic. Alkyl polyglucosides (APGs) have been suggested as additives improving lubricating properties of water. They are biodegradable and do not have to be recycled. They exhibit surface activity. They produce micelles at low concentration and lyotropic liquid crystals at high concentration. Two types of alkyl polyglucosides differing in alkyl chain lengths and degrees of polymerization were used in this investigation. Tribological tests were carried out using a ball-on-disc T-11 tester. The balls were made of steel, whereas the discs were made of steel, aluminium oxide, zirconium oxide, polyamide and poly(methyl methacrylate). The description of the device and the methods has been given in the literature (Szczerek and Tuszyński in TriboTest 8:273–284, 2002). The addition of APGs improves the lubricating properties of water. The relative decrease in motion resistance and wear depends both on the type of friction couple and on the kind of alkyl polyglucoside used. The tribological test results obtained were correlated with the activity of APGs measured as wettability of friction couples by their solutions.
Friction coefficient; Wear; Lubricants; Surfactants
Five preparations used as analgesics or lubricants in surgical, obstetrical, gynecological, and investigative procedures were tested for their effect on the isolation of Chlamydia trachomatis. Three lignocaine preparations and a lubricating jelly containing 2% phenol were inhibitory to chlamydiae. In contrast, K-Y lubricating jelly was relatively nontoxic to chlamydiae. Since K-Y jelly also had only slight toxic activity against gonococci, it is recommended for the lubrication of instruments which need to be used for the efficient isolation of these microorganisms.
Cytokine regulation of synovial fluid (SF) lubricants, hyaluronan (HA), and proteoglycan 4 (PRG4) is important in health, injury, and disease of synovial joints, and may also provide powerful regulation of lubricant secretion in bioreactors for articulating tissues. This study assessed lubricant secretion rates by human synoviocytes and the molecular weight (MW) of secreted lubricants in response to interleukin (IL)-1β, IL-17, IL-32, transforming growth factor-beta 1 (TGF-β1), and tumor necrosis factor-alpha (TNF-α), applied individually and in all combinations. Lubricant secretion rates were assessed using ELISA and binding assays, and lubricant MW was assessed using gel electrophoresis and Western blotting. HA secretion rates were increased ∼40-fold by IL-1β, and increased synergistically to ∼80-fold by the combination of IL-1β + TGF-β1 or TNF-α + IL-17. PRG4 secretion rates were increased ∼80-fold by TGF-β1, and this effect was counterbalanced by IL-1β and TNF-α. HA MW was predominantly <1 MDa for controls and individual cytokine stimulation, but was concentrated at >3 MDa after stimulation by IL-1β + TGF-β1 + TNF-α to resemble the distribution in human SF. PRG4 MW was unaffected by cytokines and similar to that in human SF. These results contribute to an understanding of the relationship between SF cytokine and lubricant content in health, injury, and disease, and provide approaches for using cytokines to modulate lubricant secretion rates and MW to help achieve desired lubricant composition of fluid in bioreactors.
Once considered unique to the lung, surfactant proteins have been clearly identified in the intestine and peritoneum and are suggested to exist in several other organs. In the lung, surfactant proteins assist in the formation of a monolayer of surface-active phospholipid at the liquid–air interface of the alveolar lining, reducing the surface tension at this surface. In contrast, surface-active phospholipid adsorbed to articular surfaces has been identified as the load-bearing boundary lubricant of the joint. This raises the question of whether surfactant proteins in synovial fluid (SF) are required for the formation of the adsorbed layer in normal joints. Proteins from small volumes of equine SF were resolved by 1- and 2-dimensional polyacrylamide gel electrophoresis and detected by Western blotting to investigate the presence of surfactant proteins. The study showed that surfactant proteins A and D (SP-A and SP-D) are present in the SF of normal horses. We suggest that, like surface-active phospholipid, SP-A and SP-D play a significant role in the functioning of joints. Next will be clarification of the roles of surfactant proteins as disease markers in a variety of joint diseases, such as degenerative joint disease and inflammatory problems.
Coital use of 1% tenofovir gel was shown to be modestly effective at preventing HIV transmission when applied vaginally in the CAPRISA 004 trial. Because the gel is hyperosmolar, which would reduce the integrity of the epithelium and induce fluid movement into the lumen, rectal use may not be acceptable. This study evaluated the pre-clinical safety and efficacy of a reformulated (reduced osmolality) tenofovir gel product.
Reduced glycerine (RG)-tenofovir gel was compared with the original tenofovir gel for physiochemical characteristics, product safety and anti-HIV-1 activity.
The formulations were similar in all characteristics except for osmolality and spreadability/firmness. The RG-tenofovir gel had a 73% lower osmolality, a 29.6% increase in spreadability and a 27% decrease in firmness as compared with the original tenofovir gel. When applied to epithelial cell monolayers, tenofovir gel showed a transient reduction in the transepithelial resistance while the RG-tenofovir gel did not. Both gels retained ectocervical and colorectal explant viability. However, tenofovir gel treatment resulted in epithelial stripping that was absent after RG-tenofovir gel treatment of the polarized explants. Anti-HIV-1 activity was confirmed by lack of HIV-1 infection in polarized explants treated with either gel as compared with the control explants.
Reducing the osmolality of the tenofovir gel resulted in improved epithelial integrity, which suggests better safety upon rectal use. The improved gel safety did not compromise drug release or anti-HIV-1 activity. These data support the use of this gel as a dual compartment microbicide.
HIV prevention; rectal microbicide; formulation; preclinical testing; safety
Over-the-counter (OTC) feminine hygiene products come with little warning about possible side effects. This study evaluates in-vitro their effects on Lactobacillus crispatus, which is dominant in the normal vaginal microbiota and helps maintain a healthy mucosal barrier essential for normal reproductive function and prevention of sexually transmitted infections and gynecologic cancer.
A feminine moisturizer (Vagisil), personal lubricant, and douche were purchased OTC. A topical spermicide (nonoxynol-9) known to alter the vaginal immune barrier was used as a control. L. crispatus was incubated with each product for 2 and 24h and then seeded on agar for colony forming units (CFU). Human vaginal epithelial cells were exposed to products in the presence or absence of L. crispatus for 24h, followed by epithelium-associated CFU enumeration. Interleukin-8 was immunoassayed and ANOVA was used for statistical evaluation.
Nonoxynol-9 and Vagisil suppressed Lactobacillus growth at 2h and killed all bacteria at 24h. The lubricant decreased bacterial growth insignificantly at 2h but killed all at 24h. The douche did not have a significant effect. At full strength, all products suppressed epithelial viability and all, except the douche, suppressed epithelial-associated CFU. When applied at non-toxic dose in the absence of bacteria, the douche and moisturizer induced an increase of IL-8, suggesting a potential to initiate inflammatory reaction. In the presence of L. crispatus, the proinflammatory effects of the douche and moisturizer were countered, and IL-8 production was inhibited in the presence of the other products.
Some OTC vaginal products may be harmful to L. crispatus and alter the vaginal immune environment. Illustrated through these results, L. crispatus is essential in the preservation of the function of vaginal epithelial cells in the presence of some feminine hygiene products. More research should be invested toward these products before they are placed on the market.
Lactobacillus; L. crispatus; cytokines; Interleukin-8; Nonoxynol-9; vaginal microbiota; vaginal epithelial colonization; mucosal immunity
Mammalian airways are protected from infection by a thin film of airway surface liquid (ASL) which covers airway epithelial surfaces and acts as a lubricant to keep mucus from adhering to the epithelial surface. Precise regulation of ASL volume is essential for efficient mucus clearance and too great a reduction in ASL volume causes mucus dehydration and mucus stasis which contributes to chronic airway infection. The epithelial Na+ channel (ENaC) is the rate-limiting step that governs Na+ absorption in the airways. Recent in vitro and in vivo data have demonstrated that ENaC is a critical determinant of ASL volume and hence mucus clearance. ENaC must be cleaved by either intracellular furin-type proteases or extracellular serine proteases to be active and conduct Na+, and this process can be inhibited by protease inhibitors. ENaC can be regulated by multiple pathways, and once proteolytically cleaved ENaC may then be inhibited by intracellular second messengers such as cAMP and PIP2. In the airways, however, regulation of ENaC by proteases seems to be the predominant mode of regulation since knockdown of either endogenous serine proteases such as prostasin, or inhibitors of ENaC proteolysis such as SPLUNC1, has large effects on ENaC activity in airway epithelia. In this review, we shall discuss how ENaC is proteolytically cleaved, how this process can regulate ASL volume, and how its failure to operate correctly may contribute to chronic airway disease.
Na+ channel; Cystic fibrosis; Epithelial transport; Fluid absorption; Lung liquid
Among the sexual minority groups, the Men who have Sex with Men (MSM) community is a large and scattered network. Sexual activity among MSM is frequent and often unplanned. STI and HIV are major medical problems faced by this vulnerable group. Stigma and discrimination towards this group result in poor access to preventive services that encourage condom and lubricant usage.
A cross-sectional, community-based study of 309 MSM was carried out in the Davangere district between December 2008 and February 2010. Participants were identified in three stages: cruising venue identification and mapping; determining eligibility and willingness to participate; and recruitment to the study. Consecutive sampling was used to recruit the participants with the help of a snowball technique, obtaining informed and written consent.
Of the participants 79.61% and 88.03% reported inconsistent use of condom and lubricant during the three months prior to the interview, respectively. In multivariate analysis, middle socioeconomic class, sex in a public place and increased frequency of sex were significantly associated with inconsistent condom use. Whereas, practising both types of anal sex (receptive and insertive), not using a condom during the last sexual encounter and increased frequency of sex were significantly associated with inconsistent lubricant use.
Many social and behavioural factors are involved in the inconsistent use of condom and lubricant among MSM. Preventive programmes must identify these factors in order to target consistent condom and lubricant use among the MSM community.
Inconsistent condom use; Men who have Sex with Men; Human Immunodeficiency Virus; Sexual risk behaviour
During joint articulation, cartilage is subjected to compression, shear, and sliding, mechanical factors that regulate and affect cartilage metabolism. The objective of this study was to use an in vitro material-on-cartilage shear test to elucidate the effects of counter-surface roughness (Polished, Mildly rough, and Rough), lubricants (phosphate buffered saline (PBS) and bovine synovial fluid (bSF)), and compression offset on the shearing and sliding of normal human talar cartilage under dynamic lateral displacement. Peak shear stress (σxz,m) and strain (Exz,m) increased with increasing platen roughness and compression offset, and were 30% higher with PBS than with bSF. Compared to PBS, bSF was more effective as a lubricant for P than for M and R platens as indicated by the higher reduction in kinetic friction coefficient (−60% vs. − 20% and −19%, respectively), σxz,m (−50% vs. −14% and −17%) and Exz,m (−54% vs. −19% and − 17%). Cartilage shear and sliding were evident for all counter-surfaces either at low compression offset (10%) or with high lateral displacement (70%), regardless of lubricant. An increase in tissue shear occurred with either increased compression offset or increased surface roughness. This material and biomechanical test system allow control of cartilage σxz,m and Exz,m, and hence, sliding magnitude, for an imposed lateral displacement. It therefore can facilitate study of cartilage mechanobiological responses to distinct regimes of cartilage loading and articulation, such as shear with variable amounts of sliding.
Cartilage; Biomechanics; Shear; Surface Roughness; Friction
Aim of this study was to prepare polyamine-conjugated PAMAM dendrimers and study their permeability across Caco-2 cell monolayers. Polyamines, namely, arginine and ornithine were conjugated to the amine terminals of the G4 PAMAM dendrimers by Fmoc synthesis. The apical-to-basolateral (AB) and basolateral-to-apical (BA) apparent permeability coefficients (Papp) for the PAMAM dendrimers increased by conjugating the dendrimers with both of the polyamines. The enhancement in permeability was dependent on the dendrimer concentration and duration of incubation. The correlation between monolayer permeability and the decrease in transepithelial electrical resistance (TEER) with both the PAMAM dendrimers and the polyamine-conjugated dendrimers suggests that paracellular transport is one of the mechanisms of transport across the epithelial cells. Cytotoxicity of the polyamine-conjugated dendrimers was evaluated in Caco-2 cells by MTT (methylthiazoletetrazolium) assay. Arginine-conjugated dendrimers were slightly more toxic than PAMAM dendrimer as well as ornithine-conjugated dendrimers. Though investigations on the possible involvement of other transport mechanisms are in progress, results of the present study suggest the potential of dendrimer-polyamine conjugates as drug carriers to increase the oral absorption of drugs.
To compare equine synovial fluid (eSF) from post-injury and control joints for (1) cartilage boundary lubrication function, (2) putative boundary lubricant molecules hyaluronan (HA), proteoglycan-4 (PRG4), and surface-active phospholipids (SAPL), (3) relationships between lubrication function and composition, and (4) lubrication restoration by addition of HA.
eSF from normal (NL), acute injury (AI), and chronic injury (CI) joints were analyzed for boundary lubrication of normal articular cartilage as kinetic friction coefficient (μkinetic). eSF were also analyzed for HA, PRG4, and SAPL concentrations and HA molecular weight (MW) distribution. The effect of addition of HA, of different concentrations and MW, to AI- and NL-eSF samples on μkinetic was determined.
The μkinetic of AI-eSF (0.036) was higher (+39%) than that of NL-eSF (0.026). Compared to NL-eSF, AI-eSF had a lower HA concentration (−30%) of lower MW forms, higher PRG4 concentration (+83%), and higher SAPL concentration (+144%). CI-eSF had μkinetic, HA, PRG4, and SAPL characteristics intermediate to that of AI-eSF and NL-eSF. Regression analysis revealed that μkinetic decreased with increasing HA concentration in eSF. The friction-reducing properties of HA alone improved with increasing concentration and MW. Addition of high-MW HA (4,000kDa) to AI-eSF reduced μkinetic to a value near that of NL-eSF.
In the acute post-injury stage, eSF exhibits poor boundary lubrication properties as indicated by a high μkinetic. HA of diminished concentration and MW may be the basis for this, and adding HA to deficient eSF restored lubrication function.
Symptomatic osteoarthritis (OA) is a common painful disease with limited treatment options. A rising number of OA patients have been treated with intraarticular injections of hyaluronic acid, including the high molecular weight hylan G-F 20, which is injected following arthrocentesis. This study investigated the effectiveness of hylan G-F 20 to lower coefficient of friction (COF) and prevent chondrocyte apoptosis in vitro.
A disc-on-disc bovine cartilage bearing was used to measure the static and kinetic COF when lubricated with hylan G-F 20, human synovial fluid (HSF) and phosphate buffered saline (PBS). Following friction testing, we stained paraffin embedded sections of these cartilage bearings for activated caspase-3, a marker of apoptosis.
Bearings lubricated with hylan G-F 20 had kinetic COF values that were similar to bearings lubricated with PBS, but significantly higher than those lubricated with HSF. There were no significant differences in static COF values in bearings lubricated with hylan G-F 20 as compared to PBS or HSF. However, bearings lubricated with HSF had a significantly lower static COF values compared to bearings lubricated with PBS. The mean percentage of caspase-3 positive chondrocytes in the superficial and upper intermediate zones of bearings lubricated with hylan G-F 20 were significantly higher when compared to bearings lubricated with HSF or unloaded controls, but significantly lower than those lubricated with PBS.
These findings indicate that joint lubrication may prevent chondrocyte apoptosis by lowering the COF. Furthermore, removal of synovial fluid prior to hylan G-F 20 injection may be detrimental to cartilage health.
articular cartilage; chondrocyte; apoptosis; synovial fluid; hylan
Two decades ago, the literature dealing with the possible applications of low molar mass liquid crystals, also called monomer liquid crystals (MLCs), only included about 50 references. Today, thousands of papers, conference reports, books or book chapters and patents refer to the study and applications of MLCs as lubricants and lubricant additives and efforts are made to develop new commercial applications. The development of more efficient lubricants is of paramount technological and economic relevance as it is estimated that half the energy consumption is dissipated as friction. MLCs have shown their ability to form ordered boundary layers with good load-carrying capacity and to lower the friction coefficients, wear rates and contact temperature of sliding surfaces, thus contributing to increase the components service life and to save energy. This review includes the use of MLCs in lubrication, and dispersions of MLCs in conventional polymers (PDMLCs). Finally, new lubricating system composed of MLC blends with surfactants, ionic liquids or nanophases are considered.
monomer liquid crystals; lubrication; tribology
Topical microbicides that block the sexual transmission of HIV and herpes simplex virus 2 (HSV-2) are desperately needed to reduce the incidence of HIV infections worldwide. Previously we completed phase 3 testing of the carrageenan-based gel Carraguard. Although the trial did not show that Carraguard is effective in preventing HIV transmission during vaginal sex, it did show that Carraguard is safe when used weekly for up to 2 years. Moreover, Carraguard has in vitro activity against human papillomavirus (HPV) and HSV-2 and favorable physical and rheological properties, which makes it a useful vehicle to deliver antiviral agents such as zinc acetate. To that end, we previously reported that a prototype zinc acetate carrageenan gel protects macaques against vaginal challenge with combined simian-human immunodeficiency virus reverse transcriptase (SHIV-RT). Herein, we report the safety and efficacy of a series of zinc acetate and/or carrageenan gels. The gels protected mice (75 to 85% survival; P < 0.001) against high-dose (106-PFU) HSV-2 vaginal or rectal challenge. In contrast, zinc acetate formulated in HEC (hydroxyethylcellulose; or the Universal Placebo) failed to protect mice against the high-dose vaginal HSV-2 challenge (similar to aqueous zinc acetate solution and the placebo controls). The gels were found to be effective spreading gels, exhibited limited toxicity in vitro, caused minimal damage to the architecture of the cervicovaginal and rectal mucosae in vivo, and induced no increased susceptibility to HSV-2 infection in a mouse model. Our results provide a strong rationale to further optimize and evaluate the zinc acetate/carrageenan gels for their ability to block the sexual transmission of HIV and HSV-2.
Anti-HIV microbicides are being investigated in clinical trials and understanding how promising strategies work, coincident with demonstrating efficacy in vivo, is central to advancing new generation microbicides. We evaluated Carraguard® and a new generation Carraguard-based formulation containing the non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 (PC-817). Since dendritic cells (DCs) are believed to be important in HIV transmission, the formulations were tested for the ability to limit DC-driven infection in vitro versus vaginal infection of macaques with RT-SHIV (SIVmac239 bearing HIV reverse transcriptase). Carraguard showed limited activity against cell-free and mature DC-driven RT-SHIV infections and, surprisingly, low doses of Carraguard enhanced infection. However, nanomolar amounts of MIV-150 overcame enhancement and blocked DC-transmitted infection. In contrast, Carraguard impeded infection of immature DCs coincident with DC maturation. Despite this variable activity in vitro, Carraguard and PC-817 prevented vaginal transmission of RT-SHIV when applied 30 min prior to challenge. PC-817 appeared no more effective than Carraguard in vivo, due to the limited activity of a single dose of MIV-150 and the dominant barrier effect of Carraguard. However, 3 doses of MIV-150 in placebo gel at and around challenge limited vaginal infection, demonstrating the potential activity of a topically applied NNRTI. These data demonstrate discordant observations when comparing in vitro and in vivo efficacy of Carraguard-based microbicides, highlighting the difficulties in testing putative anti-viral strategies in vitro to predict in vivo activity. This work also underscores the potential of Carraguard-based formulations for the delivery of anti-viral drugs to prevent vaginal HIV infection.