Assessment of gold nanoparticles as a size-dependent vaccine carrier for enhancing the antibody response against synthetic foot-and-mouth disease virus peptide.

To assess the ability of gold nanoparticles (GNPs) to act as a size-dependent carrier, a synthetic peptide resembling foot-and-mouth disease virus (FMDV) protein was conjugated to GNPs ranging from 2 to 50 nm in diameter (2, 5, 8, 12, 17, 37, and 50 nm). An extra cysteine was added to the C-terminus of the FMDV peptide (pFMDV) to ensure maximal conjugation to the GNPs, which have a high affinity for sulfhydryl groups. The resultant pFMDV-GNP conjugates were then injected into BALB/c mice. Immunization with pFMDV-keyhole limpet hemocyanin (pFMDV-KLH) conjugate was also performed as a control. Blood was obtained from the mice after 4, 6, 8, and 10 weeks and antibody titers against both pFMDV and the carriers were measured. For the pFMDV-GNP immunization, specific antibodies against the synthetic peptide were detected in the sera of mice injected with 2, 5, 8, 12, and 17 nm pFMDV-GNP conjugates. Maximal antibody binding was noted for GNPs of diameter 8-17 nm. The pFMDV-GNPs induced a three-fold increase in the antibody response compared to the response to pFMDV-KLH. However, sera from either immunized mouse group did not exhibit an antibody response to GNPs, while the sera from pFMDV-KLH-immunized mice presented high levels of binding activity against KLH. Additionally, the uptake of pFMDV-GNP in the spleen was examined by inductively coupled plasma mass spectroscopy (ICP-MS) and transmission electron microscopy (TEM). The quantity of GNPs that accumulated in the spleen correlated to the magnitude of the immune response induced by pFMDV-GNP. In conclusion, we demonstrated the size-dependent immunogenic properties of pFMDV-GNP conjugates. Furthermore, we established that GNPs ranging from 8 to 17 nm in diameter may be ideal for eliciting a focused antibody response against a synthetic pFMDV peptide.

Assessment of the In Vivo Toxicity of Gold Nanoparticles.

The environmental impact of nanoparticles is evident; however, their toxicity due to their nanosize is rarely discussed. Gold nanoparticles (GNPs) may serve as a promising model to address the size-dependent biological response to nanoparticles because they show good biocompatibility and their size can be controlled with great precision during their chemical synthesis. Naked GNPs ranging from 3 to 100 nm were injected intraperitoneally into BALB/C mice at a dose of 8 mg/kg/week. GNPs of 3, 5, 50, and 100 nm did not show harmful effects; however, GNPs ranging from 8 to 37 nm induced severe sickness in mice. Mice injected with GNPs in this range showed fatigue, loss of appetite, change of fur color, and weight loss. Starting from day 14, mice in this group exhibited a camel-like back and crooked spine. The majority of mice in these groups died within 21 days. Injection of 5 and 3 nm GNPs, however, did not induce sickness or lethality in mice. Pathological examination of the major organs of the mice in the diseased groups indicated an increase of Kupffer cells in the liver, loss of structural integrity in the lungs, and diffusion of white pulp in the spleen. The pathological abnormality was associated with the presence of gold particles at the diseased sites, which were verified by ex vivo Coherent anti-Stoke Raman scattering microscopy. Modifying the surface of the GNPs by incorporating immunogenic peptides ameliorated their toxicity. This reduction in the toxicity is associated with an increase in the ability to induce antibody response. The toxicity of GNPs may be a fundamental determinant of the environmental toxicity of nanoparticles.

Quality-initiated prophylactic antibiotic use in laparoscopic-assisted vaginal hysterectomy.

BACKGROUND: An evidence-based initiation of quality improvement activity for reducing the usage of prophylactic antibiotic in laparoscopic-assisted vaginal hysterectomy (LAVH) in a tertiary hospital. AIMS: The authors investigated whether single or multiple doses of cefazoline were more cost-effective in preventing postoperative infection associated with LAVH. METHODS: The study groups comprised of 310 patients who had undergone LAVH continuously in a medical centre. Patients were divided into two groups on the basis of whether they received a single dose or multiple doses (range: two to four doses) of cefazoline during the perioperative period. Postoperative infections such as pelvic cellulitis or abscess, vaginal cuff abscess, wound infection and urinary tract infection that occurred either during hospitalisation or within one month after discharge were observed and recorded. Incremental cost-effectiveness ratio (ICER) was calculated using the mean direct drug cost and the prophylactic effect of infection in both groups. RESULTS: The prophylactic effect of infection was similar in the single-dose group and the multiple-dose group (94.6% vs 93.9%, P = 0.986). The ICER was significantly lower in the single-dose group (153.3 vs 460.4, P < 0.001). CONCLUSIONS: The result revealed that a single dose of cefazoline is more cost-effective than multiple doses in the prevention of infection associated with LAVH. It fulfils the goal of cost minimisation and quality of care in today's environment of medical cost containment.

Short course of prophylactic antibiotics in laparoscopically assisted vaginal hysterectomy.

OBJECTIVE: To evaluate whether a short course of prophylactic antibiotics is as efficacious as a longer course in laparoscopically assisted vaginal hysterectomy (LAVH). STUDY DESIGN: A total of 156 patients who underwent LAVH were included in the study; 82 received a long course of combined prophylactic antibiotics, and 74 received a short course, administered for < 24 hours during the perioperative period. The subjects were randomly assigned using a computer-generated schedule. Data regarding resource consumption were collected from the hospital's electronic database. Patient characteristics and medical care process data were collected from the patient charts. Student's t test was used to determine the statistical significance of the differences between continuous variables in the 2 groups of patients. The chi2 test was used to measure the statistical significance of differences between nominal variables in the 2 groups. RESULTS: The short course significantly influenced the number of injected vials of antibiotics, the antibiotic fee and the total admission fee. The average total admission fee decreased by 2.3% (p = 0.034), and the average antibiotic-fee dropped by 68.4% (p < 0.01). The average injected vials of cephalothin decreased by 4.3, and the vials of gentamycin decreased by 3.3 (p < 0.01). As for the rate of operative site infection and urinary tract infection during hospitalization and within 7 days of discharge, no statistical differences were found between the 2 groups (p = 0.735; p = 0.917). CONCLUSION: This pilot study revealed that a short course of prophylactic antibiotics was as efficacious as a longer course in preventing postoperative infection. It was also cost-effective.