Using probe-microphone measurements to improve the match to target gain and frequency response slope, as a function of earmould style, frequency, and input level.

OBJECTIVE: Matching a prescription gain target at 60-65 dB SPL does not ensure audibility of lower input levels, nor does it mean the fitted frequency response slope is conducive to good sound quality. The aim of the present study was to evaluate the use of probe-microphone measurements to match target gain and slope, as a function of earmould style, frequency, and input level. DESIGN: The real-ear insertion gain was calculated for an input of 50, 65, and 80 dB SPL for the manufacturer's 'initial fit' (IF) settings and after adjustment to target in 49 and 51 open slim-tube and custom earmould fittings, respectively. STUDY SAMPLE: One hundred adults with median age 74 years (range 32-93). RESULTS: Some 18%-67% of the IF settings were within 10 dB of the target gain but this increased to >85% after adjustment. Some 47%-71% of the IF settings were within 10 dB of the target slope but, with the exception of 2-4 kHz, this increased to >88% after adjustment. CONCLUSIONS: The results indicate that IF settings are inadequate, at least for the model of hearing aid used in the present study; however, significant discrepancies remained, even after adjustment.

Cellular uptake and cytotoxicity studies of pH-responsive polymeric nanoparticles fabricated by dispersion polymerization.

OBJECTIVE: A strategy in site-specific drug delivery is the use of pH-gradients that exist in diseased conditions such as cancer for the release of loaded drug(s) in the biophase. The objective of this work is to synthesize pH-responsive docetaxel-loaded nanoparticles with a bisacrylate acetal crosslinker, which can get internalized into cells, and which will be equivalent to or more cytotoxic than the free drug against cancer cells. METHODS: pH-responsive nanoparticles were synthesized by a dispersion polymerization technique. The nanoparticles were characterized for physicochemical properties. Cytotoxicity studies of the nanoparticles were performed on PC3 and LNCaP prostate cancer cell lines using a cell viability assay. Cellular uptake studies were performed using a confocal laser scanning microscope. RESULTS: Smooth spherical nanoparticles were formed. In-vitro drug release was faster at pH 5.0 than pH 7.4, which confirmed the pH-responsiveness of the nanoparticles. Cytotoxicity studies showed that the nanoparticles were more effective at the same molar amount than the free drug against cancer cells. Both dose exposure and incubation time affected the cytotoxicity of prostate cancer cells. Furthermore, LNCaP cells appeared to be the more sensitive to docetaxel than PC3 cells. The cellular uptake studies clearly showed the presence of discrete nanoparticles within the cells in as little as 2 hours. CONCLUSION: pH-sensitive nanoparticles were developed; they degraded quickly in the mildly acidic environments similar to those found in endosomes and lysosomes of tumor tissues. These novel pH-sensitive nanoparticles would offer several advantages over conventional drug therapies.

pH-Sensitive Polymeric Nanoparticles Fabricated by Dispersion Polymerization for the Delivery of Bioactive Agents.

BACKGROUND: Development of pH-responsive nanoparticles capable of rapid degradation in the acidic environments in the endosomes and lysosomes of tumor tissues but relatively more stable in the physiological pH (pH 7.4) is desirable. OBJECTIVE: To show that the number of methoxy groups on the benzene ring of benzaldehyde bisacrylate acetal crosslinkers should affect the rate of hydrolysis of the crosslinkers and in vitro availability of the drug loaded into the nanoparticles. METHOD: Three pH-sensitive acetal crosslinkers were synthesized and characterized by 1H NMR, 13C NMR, FT-IR and high resolution mass spectroscopy (HR-MS). The nanoparticles were fabricated by free-radical dispersion polymerization method. Hydrolysis studies were carried out on the crosslinkers and nanoparticles; drug release studies were done on docetaxel-loaded nanoparticles at pH 5.0 and pH 7.4. The statisitical experimental design was randomized complete block design followed by analyses of variance with F-test of significance. Pairwise comparison test was used to locate specific differences among parameters of the crosslinkers and the nanopaticles. RESULTS: Scanning electron micrographs showed the formation of spherical particles. Particle size analysis showed that the nanoparticles are within nanosize range with negative zeta potential. Data showed that the rate of hydrolysis and drug release were faster at pH 5.0 compared to pH 7.4. Hydrolysis and drug release studies were dependent on the structure of the acetals: Di(2-methacryloyloxyethoxy)- [2,4,6-trimethoxyphenyl] methane crosslinker showed the fastest rate of hydrolysis, followed by di(2- methacryloyloxyethoxy)-[2,4-dimethoxyphe-nyl] methane and di(2-methacryloyloxyethoxy)-[4-methoxyphenyl] methane. CONCLUSION: The pH-responsive nanoparticles are suitable for the delivery of bioactive agents, especially anticancer drugs.