Influence of nanocrystal size on the in vivo absorption kinetics of caffeine after topical application.

The absorption of topically applied substances is challenging due to the effective skin barrier. Encapsulation of substances into nanoparticles was expected to be promising to increase the bioavailability of topically applied products. Since nanoparticles cannot traverse the intact skin barrier, but penetrate into the hair follicles, they could be used to deliver substances via hair follicles, where the active is released and can translocate independently transfollicularly into the viable epidermis. In the present in vivo study, this effect was investigated for caffeine. Caffeine nanocrystals of two sizes, 206 nm and 694 nm, with equal amounts of caffeine were used to study caffeine serum concentration kinetics after topical application on 5 human volunteers. The study demonstrated that at early time points, the smaller nanocrystals were more effective in increasing the bioavailability of caffeine, whereas after 20 min, the serum concentration of caffeine was higher when caffeine was applied by larger nanocrystals. Caffeine was still detectable after 5 days. The area under the curve could be increased by 82% when the 694 nm nanocrystals were applied. Especially larger sized nanocrystals seem to be a promising type of nanoparticulate preparation to increase the bioavailability of topically applied drugs via the transfollicular penetration pathway.

Health Equity, Cuban Style.

The United States has not yet decided to ensure that every citizen has access to health care services at reasonable cost. The United States spends more on health care than any other country by far. Yet the health status of the US population, when compared with that of like nations, remains poor. The US system does not operate efficiently, fares poorly in terms of health equity, and has an illness and injury care industry with many uncoordinated "systems" focused on treating individuals rather than on improving health status. There are lessons for us in Cuba's health system.

Public health preparedness and response competency model methodology.

OBJECTIVE: The Pandemic and All-Hazards Preparedness Act calls for establishing a competency-based training program to train public health practitioners. To inform such training, the Centers for Disease Control and Prevention and the Association of Schools of Public Health managed groups of experts to produce a competency model which could function as a national standard of behaviorally based, observable skills for the public health workforce to prevent, protect against, respond to, and recover from all hazards. DESIGN: A systematic review of existing competency models generated a competency model of proposed domains and competencies. PARTICIPANTS: National stakeholders were engaged to obtain consensus through a three-stage Delphi-like process. RESULTS: The Delphi-like process achieved 84 percent, 82 percent, and 79 percent response rates in its three stages. Three hundred sixty six unique individuals responded to the three-round process, with 45 percent (n = 166) responding to all three rounds. The resulting competency model features 18 competencies within four core learning domains targeted at midlevel public health workers. CONCLUSIONS: Practitioners and academics have adopted the Public Health Preparedness and Response Core Competency Model, some of whom have formed workgroups to develop curricula based on the model. Efforts will be needed to develop evaluation materials for training and education programs to refine the model as well as for future training and education initiatives.

Azithromycin nanocrystals for dermal prevention of tick bite infections.

Azithromycin was optimized as nanocrystals with a drug content of 10.0 % (w/w) and a surfactant D-α -tocopheryl polyethylenglycol 1000 succinate (TPGS) content of 1.0 % (w/w) using bead milling for 10 min. The photon correlation spectroscopy (PCS) diameter of the bulk population was 189 nm, laser diffraction (LD) diameter 90 % was 370 nm. Spherical morphology of the optimal nanocrystals was observed by transmission electron microscope (TEM). They were stable over 1 year of storage at 4 °C with the particle size within the nanometer range which was confirmed by PCS, LD and light microscope. An acceptable physical stability of 2 years was also obtained when stored at 4 °C. No microbial attack to the nanocrystals was observed before 3 years storage at 4 °C. The saturation solubility of the nanocrystals was up to triple compared to the raw drug powder (RDP) in water. When incorporated into the gel base, highest penetration efficacy was achieved by the optimal nanocrystals compared to 1) the clinically effective ethanol-solution-gel, 2) the gel with propylene glycol and 3) the gel with RDP in the ex vivo porcine ear penetration study. Even though propylene glycol improved saturation solubility of nanocrystals, it could not bring benefit to nanocrystals in the penetration study. Based on these optimized azithromycin nanocrystals, topical administration for enhanced dermal bioavailability of azithromycin seems to be feasible.

Maximum Loaded Amorphous Azithromycin Produced Using the Wetness Impregnation Method with Fractional Steps for Dermal Prophylaxis Against Lyme Disease.

Azithromycin was loaded onto the µm-sized mesoporous silica Davisil® SP53D-11920 using the wetness impregnation method with fractional steps (WIFS) and further incorporated into a 5 % hydroxypropyl cellulose gel to prevent Lyme disease. Maximum loadings (32.0 % w/w and 33.2 % w/w) were produced by different concentrated loading solutions and determined by X-ray diffraction (XRD). A total of 24 months stability of the amorphous azithromycin state in the silica (33.2 % loading) and 18 months stability in the gel (33.2 % loading) at 4 °C were also confirmed by XRD. The higher kinetic solubility at 40 min (1,300 µg/mL versus 93 µg/mL) and higher porcine ear skin penetration compared to the raw drug powder indicated higher dermal bioavailability of the azithromycin-loaded silica (32.0 % loading), even when compared to the "gold standard" nanocrystals and another clinical effective azithromycin formulation with ethanol. In summary, maximum loaded silicas with azithromycin by WIFS is a promising dermal formulation for prophylaxis against Lyme disease.

Evaluation of a biosurfactant extract obtained from corn for dermal application.

At present, there is an increasing demand to improve the sustainability of surface-active compounds in dermal formulations. Biosurfactants, which are derived from living cells, are considered to be more environmentally friendly than synthetic surfactants. Thus, the use of biosurfactants is a promising strategy for the formulation of more environmentally friendly and sustainable dermal products. In this work, a biosurfactant extract (BS) obtained from corn wet-milling industry was studied for its potential use in dermal formulations. The corn derived BS possesses good surface-active properties and was found to be a suitable co-stabilizer for nanoemulsions and nanocrystals for dermal application. It also possesses antioxidative and skin protective properties and was also able to increase the dermal penetration efficacy for lipophilic actives. In dermal formulations the BS can therefore be used as co-stabilizer with antioxidative and penetration enhancing properties at the same time.

Development of a Research Agenda Focused on Academic Health Departments.

An academic health department (AHD) is a formal partnership between an academic institution and a governmental public health agency. Case studies have described the value of individual AHDs in the areas of student engagement, practice-based research, workforce development, and service. With growing interest in AHDs and the increasing importance of academic-practice linkages in both academic programs' and public health agencies' accreditation processes, articulating a research agenda focused on the AHD model can be useful for stimulating the research and practice fields to further develop the evidence base for AHDs. We provide a research agenda, developed through an iterative process involving academicians, practitioners, and others interested in academic-practice linkages.

Partial break in tolerance of NKG2A-/LIR-1- single KIR+ NK cells early in the course of HLA-matched, KIR-mismatched hematopoietic cell transplantation.

Natural killer (NK) cell subpopulations from 8 HLA-matched but killer cell immunoglobulin-like receptor (KIR)/HLA-ligand-mismatched patient-donor pairs were analyzed in the course of allogeneic hematopoietic stem cell transplantation (HCT). The patients' post-transplantation NKG2A-/LIR-1- NK cells, which expressed only inhibitory KIRs for which the patient had no HLA class I ligands, showed higher cytotoxic capacity than the NKG2A-/LIR-1- NK cells lacking any inhibitory KIRs that remained tolerant throughout the course of HCT. The NKG2A+ NK cell subpopulations displayed the highest levels of cytotoxic activation, which appeared to be significantly enhanced in comparison with that in allogeneic graft's donors. LIR-1- NK cells were much more frequent after HCT than LIR-1+ NK cells and LIR-1 expression on NKG2A+ or NKG2A- NK cells was associated with significantly lower cytotoxic activities. Thus NKG2A-/LIR-1- NK cells expressing only HLA-mismatched KIRs show a partial break in tolerance in the first year following HCT. The failure to exclude LIR-1+ cells within the NKG2A- NK cell subset in previous studies could explain the earlier conflicting results. Thus systemic immune activation in patients following HCT augments the GvL effect through both increasing overall NK cell activities and partially breaking tolerance of unlicensed NK cells.

Mucoadhesive dexamethasone acetate-polymyxin B sulfate cationic ocular nanoemulsion--novel combinatorial formulation concept.

Dexamethasone acetate (DEX) and polymyxin B sulfate (polymyxin B) were formulated as a cationic nanoemulsion for the treatment of ophthalmic infections. As novel concept, the positive charge to achieve mucoadhesion was not generated by toxicologically and regulatorily problematic cationic lipids or polymers, but by using a positively charged drug in combination with positively charged preservatives. The preservative also acts as co-surfactant to stabilize the emulsion. Nanoemulsions with the lipid phase Eutanol G-Lipoid S 100 (70%:30%) containing 0.05% (w/w) DEX were produced by high pressure homogenization, followed by dissolving the hydrophilic molecules in the water phase, e.g. polymyxin B (0.1%, w/w), cetylpyridinium chloride (0.01%, w/w) and glycerol (2.6%, w/w) to yield a combination product. The particles were below 200 nm with narrow size distribution. The osmolality (374 mOsm/kg), pH (5.31) and viscosity (2.45 mPa s at 37 degrees C) were compatible to the ocular administration. The zeta potential of the optimized formulation was shifted from approx. +9 mV to -11 mV after mucin incubation. The in vitro test revealed no potential cytotoxicity. The final products were stable after 180 days of storage at 4 degrees C and room temperature. The developed product is a viable alternative to the commercial ophthalmic suspensions. Moreover, this concept of generating the positive charge by cationic drug and/or preservative addition can be transferred to other ophthalmic products.

Characteristics of Academic Health Departments: Initial Findings From a Cross-Sectional Survey.

Academic Health Departments (AHDs) represent collaborative relationships between public health academia and practice. The purpose of this study was to gain a better understanding of AHD characteristics, to document the extent of collaboration between organizations in an AHD, and to explore the benefits of AHDs. An electronic survey on the AHD was sent to members of the AHD Learning Community--a virtual learning community with 338 members. There were 110 valid responses to the survey, with 65 indicating they were currently in an AHD partnership. Thirty-two percent of AHDs had been established for more than 10 years; 64% were engaged in joint research activities; and, while 92% of respondents placed a high value on improving the competencies of students, almost half placed a high value on improving the competencies of faculty. This study can be a springboard for further research on the impact of AHDs on practice, academia, and ultimately community health.

High Estradiol Levels During Postmenopause - Pitfalls in Laboratory Analysis.

A 54-year-old woman was admitted with a result of high serum estradiol levels (> 4300 pg/ml) and typical postmenopausal symptoms. She had a history of an adnexectomy (normal histopathology) due to the elevated estradiol levels. After surgery, estradiol levels were as high as before. Analyzing the anti-mullerian hormone (AMH), inhibin B, DHEA-S and estrone, typical postmenopausal levels were found. Serum estradiol levels were controlled several times with rabbit-derived polyclonal as well as monoclonal antibodies to optimize the selectivity of the test system. Secondary, a radioimmunoassay was performed to exclude interferences of the detection system where lower, but still elevated estradiol levels (186 pg/ml) were found. Hypothesizing that our patient underwent a cross reaction with irregular antibodies, a control was done using sheep-derived antibodies, which proved a postmenopausal hormone level (estradiol level < 5 pg/ml). This result was confirmed using a fluorescence enzyme immunoassay (FEIA) revealing high levels of irregular antibodies (> 200 mg/l; reference < 30 mg/l). This case depicts the pitfalls of estradiol measurement detecting false elevated estradiol levels in a postmenopausal woman.

Nanosuspensions of hesperetin: preparation and characterization.

Nanosuspensions are a smart formulation principle for dermal applications, as they increase the penetration of poorly soluble substances into the skin. Because microbial stability is a pre-requisite for dermal formulations, water containing formulations need to be preserved. Preservatives are known to possibly impair the physical stability of disperse systems, i.e. by causing agglomeration. These aggregation phenomena might occur during storage of the final product, but can already occur during the production process itself. Therefore, in this study the influence of six different preservatives on the diminution efficiency during the production of hesperetin nanocrystals was investigated. Particles with and without the addition of preservatives were produced by high pressure homogenization (HPH) and the final particle size was analysed and compared to the non-preserved suspension. All preservatives influenced the diminution progress during production and the final particle sizes obtained. The non-preserved suspension yielded a particle size of about 300 nm. Preservation with Hydrolite, Euxyl PE9010, Rokonsal and Phenonip led to sizes of about 400 nm. Preservation with Caprylyl glycol and MultiEx did not lead to nanoparticles (size > 1 microm) and caused a slight agglomeration of the nanosuspensions. Based on zeta potential measurements it was found that the impairment is related to the lipophilicity of the presverative, i.e. the lower the lipophilicity, the less is the impairment. In conclusion, preservatives impair the diminution efficacy during the production of nanosuspensions. Therefore, if possible, preservatives should be added to nanosuspensions after the production process. If preservatives are required during production, highly hydrophilic preservatives, e.g. Hydrolite E, should be used.

The Academic Health Department: the process of maturation.

The Academic Health Department (AHD) involves an arrangement between a governmental health agency and an academic institution, which provides mutual benefits in teaching, service, research, and practice. From its initial development in the mid-1980s as the public health equivalent of the relationship between a teaching hospital and a medical school, the AHD concept has evolved to include multiple levels of governmental public health agencies (local, state, and federal) as well as multiple academic institutions (public health, medicine, and primary care medical residencies). Throughout the decade of the 2000s, multiple influences have impacted both the quality and quantity of AHDs, leading to an expansion of AHDs through the Council on Linkages' AHD Learning Community. The value of the AHD--as described from prior studies as well as the AHD case examples in this current special issue--is evident in its impact on the quality of educational experiences and workforce development, agency and academic accreditation, practice-based research, and the potential to influence health reform.

A new concept for the treatment of atopic dermatitis: silver-nanolipid complex (sNLC).

In the treatment of mild to medium severe atopic dermatitis a new formulation proved to be highly efficient. The formulation is based on a combination of microsilver and nanolipid carriers (NLC) incorporated into an o/w cream and a lotion. A theory of action was proposed, the formation of silver-NLC complex (sNLC). In this study this theory was proven, and based on this new mechanism two new approaches for dealing with AD are suggested to distinctly improve AD treatment, i.e. increasing efficiency, reducing drug exposure and reducing side effects. The antimicrobial silver ions adsorb onto the surface of the negatively charged NLC (=sNLC complex). The sNLC as nanoparticles are highly adhesive to skin and bacterial surfaces, leading to a locally high concentration of silver ions killing the bacteria, much more effective than silver alone. The NLC restore the distorted skin barrier. Based on this a new two-step approach is suggested: (1) "treatment-supportive consumer care" by restoring the normal skin condition (NLC for barrier restoration plus synergistic antibacterial silver-NLC complex) and (2) "drug-loaded consumer care AD formulations". i.e. incorporating drugs into the NLC of this consumer care formulation. NLC incorporation makes the drugs more effective (penetration enhancement) and simultaneously exploits the skin normalization ability of the skin care sNLC formulation, future drug candidates being prednicarbate and tacrolimus.

Development of lycopene-loaded nanostructured lipid carriers: effect of rice oil and cholesterol.

Nanostructured lipid carriers (NLC) were developed using a skin-compatible surfactant and natural lipid materials (rice oil, cholesterol) to incorporate lycopene. Characteristics of the NLC were explored in comparison with nanoemulsions and solid-lipid nanoparticles (SLN). Photon correlation spectroscopy, laser diffractometry (LD) and differential scanning calorimetry were used to determine particle size and thermal stability. Particle size expressed as LD (0.99) was 405 nm for the SLN, 350 nm for the NLC without cholesterol and 287 nm for the NLC with cholesterol. Rice oil and cholesterol enabled the formation of smaller particles, but cholesterol also reduced drug stability in the NLC. To preserve chemical stability of lycopene in the NLC, cholesterol should be avoided and storage should be at 4 degrees C or at room temperature.

Public health preparedness and response competency model methodology.

OBJECTIVE: The Pandemic and All-Hazards Preparedness Act calls for establishing a competency-based training program to train public health practitioners. To inform such training, the Centers for Disease Control and Prevention and the Association of Schools of Public Health managed groups of experts to produce a competency model which could function as a national standard of behaviorally based, observable skills for the public health workforce to prevent, protect against, respond to, and recover from all hazards. DESIGN: A systematic review of existing competency models generated a competency model of proposed domains and competencies. PARTICIPANTS: National stakeholders were engaged to obtain consensus through a three-stage Delphi-like process. RESULTS: The Delphi-like process achieved 84 percent, 82 percent, and 79 percent response rates in its three stages. Three hundred sixty six unique individuals responded to the three-round process, with 45 percent (n = 166) responding to all three rounds. The resulting competency model features 18 competencies within four core learning domains targeted at midlevel public health workers. CONCLUSIONS: Practitioners and academics have adopted the Public Health Preparedness and Response Core Competency Model, some of whom have formed workgroups to develop curricula based on the model. Efforts will be needed to develop evaluation materials for training and education programs to refine the model as well as for future training and education initiatives.