Seong Bae Park

A novel pH-sensitive membrane from chitosan - TEOS IPN; preparation and its drug permeation characteristics

A novel organic-inorganic composite membrane was prepared, using tetra ethyl ortho silicate (TEOS) as an inorganic material and chitosan as an organic compound. Equilibrium and oscillatory swelling studies were conducted to investigate swelling behaviors of the membrane according to the pH of the swelling medium. Drug permeation experiments were also performed in phosphate buffer solution of the pH of 2.5 and 7.5, respectively. Lidocaine HCl, sodium salicylate and 4-acetamidophenol were selected as model drugs to examine the effect of ionic property of drug on the permeation behavior. The effects of membrane composition and the external pH on the swelling and the drug permeation behavior of IPN membrane could be summarized as follows; chitosan incorporated into TEOS IPN swelled at pH 2.5 while shrunk at pH 7.5. This swelling behavior was completely reversible and the membrane responded rapidly to the change in environmental pH condition. According to swelling behavior, an increase in pH from 2.5 to 7.5 yielded an increase in the rate of drug permeation because of the shrinking of the incorporated chitosan in TEOS IPN, while decrease in pH resulted in low permeation rate. The optimal TEOS-chitosan ratio for maximum pH-sensitivity existed and drug permeation was influenced not only with the external pH but also with the ionic interactions between the drug and membrane.

Twenty-four hour ocular perfusion pressure fluctuation and risk of normal-tension glaucoma progression.

PURPOSE To investigate the relationship between clinical factors including 24-hour mean ocular perfusion pressure (MOPP, (2/3) x mean arterial pressure [MAP] - intraocular pressure [IOP]) and visual field (VF) progression in eyes with medically treated normal-tension glaucoma (NTG). METHODS One hundred one eyes of 101 NTG patients followed up for more than 4 years (mean follow-up, 6.2 years +/- 12.1 months) were included after retrospective chart review. Several clinical factors including demographic, systemic, ocular risk factors, and 24-hour MOPP were explored for associations with decreasing VF. Kaplan-Meier analyses were performed to compare outcomes with reference to four risk factors (age, myopia, and elevated MAP and MOPP fluctuation) for VF deterioration. Hazard ratios (HRs) for the association between potential risk factors and glaucoma progression were obtained using Cox proportional hazards models. RESULTS Overall VF progression was detected in 29 (28.7%) eyes. There were significant differences between progressors and nonprogressors in nocturnal MAP and MOPP fluctuations (both P < 0.0001), 24-hour MAP, and MOPP fluctuations (both P < 0.0001), initial mean deviation (P = 0.0034), and pattern standard deviation (PSD) score (P < 0.0001). Both elevated 24-hour MAP and MOPP fluctuations were associated with greater VF progression probabilities based on Kaplan-Meier analyses. Among all risk factors investigated, the Cox proportional hazards model indicated that VF progression was significantly associated with 24-hour MOPP fluctuation and initial PSD score. CONCLUSIONS Clinical factors other than IOP were associated with VF progression in our series of medically treated NTG eyes. Twenty-four-hour MOPP fluctuation was the most consistent prognostic factor for glaucoma progression.

Magnetic poly ε-caprolactone nanoparticles containing Fe3O4 and gemcitabine enhance anti-tumor effect in pancreatic cancer xenograft mouse model

We prepared magnetic (Fe3O4) poly ε-caprolactone (PCL) nanoparticles (mean diameter 164 ± 3 nm) containing an anticancer drug (gemcitabine) using emulsion-diffusion method in order to develop more efficient drug delivery for cancer treatment. Nanoparticles were smooth, well individualized and homogeneous in size. The values of magnetizations for the magnetic PCL nanoparticles were observed around 10.2 emu/g at 2000 Oe magnetic field intensity and showed super-paramagnetic property. In case of the drug, the drug loading contents was 18.6% and entrapment efficiency was 52.2%. The anti-tumor effects caused by these particles were examined using nude mice bearing subcutaneous human pancreatic adenocarcinoma cells (HPAC) in vivo. We divided that these mice were randomly assigned to one of five treatment groups for experimental contrast. The antitumor effect was showed with 15-fold higher dose when compared to free gemcitabine. From the result, the magnetic PCL nanoparticles may provide a therapeutic benefit by delivering drugs efficiently to magnetically targeted tumor tissues, thus achieving safe and successful anti-tumor effects with low toxicity.

Comparison of retinal nerve fibre layer thickness measurements calculated by the optic nerve head map (NHM4) and RNFL3.45 modes of spectral-domain optical coherence tomography (RTVue-100)

Aim To evaluate and compare retinal nerve fibre layer (RNFL) thickness measured by direct scanning (RNFL3.45 mode) and re-sampling from datasets (NHM4 mode) of RTVue-100 optical coherence tomography (OCT). Methods Thirty-six healthy subjects and 76 subjects with glaucoma were imaged with Stratus OCT (fast RNFL mode, RNFL3) and RTVue-100 OCT (NHM4 (RNFL1) and RNFL3.45 (RNFL2) modes). Measurement reproducibility was assessed in NHM4 and RNFL3.45 modes of RTVue-100 OCT (intraclass correlation coefficient (ICC)). Agreement between different RNFL measurements was analysed by Bland–Altman plot. The areas under the receiver operating characteristic (ROC) curves (AUCs) for discrimination between healthy and glaucoma were compared between the different RNFL measurements. Results Both NHM4 and RNFL3.45 modes showed excellent measurement reproducibilities (ICC 0.831–0.978). RNFL thicknesses by two different modes of the RTVue-100 OCT, and by the Stratus OCT, were correlated in all sectors, including average. There was no significant difference between RNFL1 and RNFL2 data. However, RNFL thickness in glaucomatous eyes by the RTVue-100 OCT was significantly greater than that measured by Stratus OCT. RNFL thicknesses determined by the two different modes of RTVue-100 OCT were in excellent agreement (95% limits of agreement −6.53 to 6.95 μm). All three RNFL measurements showed good glaucoma discrimination ability (AUC = RNFL1 0.970, RNFL2 0.962, RNFL3 0.971). Conclusions RNFL thickness determined by direct scanning and re-sampling from datasets of RTVue-100 OCT were in good agreement. However, both measurements in glaucomatous subjects were significantly different from those with the Stratus OCT. Those findings should be considered when a patient is followed-up using different types of OCT.

Hydrophilic acrylic intraocular lens optic opacification in a diabetic patient

PurposeTo report clinicopathologic and ultrastructural feature of one opacified hydrophilic acrylic intraocular lens (IOL) explanted from a diabetic patient.MethodsA 48-year-old man underwent trans pars plana vitrectomy and phacoemulsification with implantation of a hydrophilic acrylic lens OS in November 2008. The patient complained of a marked decrease in visual acuity in May 2009 as a result of a milky opalescence of the IOL. Intraocular lens explantation and exchange were performed in August 2009, and the explanted IOL was submitted to our center for detailed pathologic, histochemical and ultrastructural evaluation. It was stained by the von Kossa method for calcium, and also underwent scanning electron microscopy and energy dispersive radiograph spectroscopy to ascertain the nature of the deposits leading to opacification.ResultsOpacification of the IOL was found to be the cause of the decreased visual acuity. The opacification involved only the IOL optic, and the haptics was clear. Histochemical and ultrastructural analyses revealed that the opacity was caused by deposition of calcium and phosphate within the lens optic.ConclusionWe believe this report of calcification of the Akreos® MI-60 IOL is of clinicopathological importance. Long-term follow-up of diabetic patients implanted with this IOL should be maintained by surgeons and manufacturers.

Glaucoma diagnostic performance of humphrey matrix and standard automated perimetry

PurposeTo evaluate and compare the performance of Humphrey Matrix perimetry (Matrix) and standard automated perimetry (SAP) for glaucoma discrimination.MethodsForty-seven healthy and 68 glaucomatous subjects were included in this study. Glaucoma was defined as having a glaucomatous optic disc and a nerve fiber indicator (NFI) GDx VCC scanning laser polarimetry score of >40. Glaucomatous subjects were classified into two groups, early (40 < NFI ≤ 50) and moderate to advanced (NFI > 50). The number of clusters on Matrix and SAP pattern deviation maps were estimated and scored. Areas under the receiver operating characteristic curves (AUCs) of the cluster scores were calculated for early and moderate to advanced stages of glaucoma and compared between Matrix and SAP.ResultsAmong 68 glaucomatous subjects, 24 eyes were classified as having early and 44 eyes as having moderate to advanced glaucoma. The overall AUC of the Matrix cluster score was comparable to that of SAP (0.857, 0.881, P = 0.538). The AUC of the cluster score did not reveal statistically significant differences between Matrix and SAP for either early or moderate to advanced stages of glaucoma (P = 0.831, 0.237).ConclusionBoth Matrix and SAP showed good diagnostic performance with glaucoma defined as structural loss. Matrix and SAP data showed similar discrimination capability for different stages of glaucoma determined by cluster analysis.