Search

Rajiv Bajracharya,* Kshitis Chandra Baral,* Sang Hoon Lee, Jae Geun Song, Hyo-Kyung Han College of Pharmacy, Dongguk University-Seoul, Goyang, Korea*These authors contributed equally to this workCorrespondence: Hyo-Kyung Han, College of Pharmacy, Dongguk University-Seoul, Dongguk-ro-32, Ilsan-Donggu, Goyang, Korea, Tel +82-31-961-5217, Fax +82-31-961-5206, Email hkhan@dongguk.eduPurpose: Oral administration, although convenient and preferred for treating colorectal cancer (CRC), faces challenges due to limited CRC-related intestinal positioning and a dense mucus barrier. In the present study, a gold-nanoparticle decorated–organometallic phyllosilicate nanocomposite (AC-Au), with a pH-dependent surface coating, was employed for more effective oral delivery of anticancer drugs to treat CRC.Methods: The organometallic AC-Au was synthesized using the in-situ sol-gel method. Subsequently, methotrexate (MTX) was loaded into AC-Au, and the complex (AC-Au/MTX) was surface-coated with poly (methacrylic acid-co-methyl methacrylate) (1:2), a pH-dependent polymer (E/AC-Au /MTX). The in vitro characteristics of nanoparticles were examined using various analytical methods. In vivo efficacy studies were also conducted using an HCT-116 orthotopic colorectal cancer model.Results: AC-Au emerged as a spherical nanoparticle with a mean size of 26.5 ± 0.43 nm, displaying a positive charge over the pH range of 2– 10. Both the uncoated and coated drug–loaded nanocomplexes (AC-Au/MTX and E/AC-Au/MTX) were fabricated with high entrapment efficiency (> 80%). Various analyses, including ultraviolet-visible spectroscopy, X-ray powder diffraction, transmission electron microscopy, and energy dispersive X-ray spectroscopy, confirmed the formation of the nanocomplexes. While AC-Au/MTX achieved rapid and extensive drug release at the pH range of 1.2– 7.4, E/AC-Au/MTX exhibited pH-dependent drug release, with approximately 23% at pH 1.2 and 74% at pH 7.4. Relative to free MTX, the AC-Au-based nanocomplex significantly enhanced the cytotoxicity of MTX in HCT-116 cells. Furthermore, orally administered E/AC-Au/MTX significantly improved the anti-tumor activity of MTX in an HCT-116 orthotopic colorectal cancer model, resulting in approximately 60% suppression of tumor mass compared with the positive control.Conclusion: The organometallic AC-Au nanocomplex coated with a pH-dependent polymer has the potential to be an effective colonic drug delivery system of MTX, enhancing in vivo efficacy against colorectal cancer.Keywords: methotrexate, aminoclay, gold nanoparticle, colonic delivery, cytotoxicity

Kshitis Chandra Baral, Rajiv Bajracharya, Sang Hoon Lee, Hyo-Kyung Han BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang, 10326, KoreaCorrespondence: Hyo-Kyung HanBK21 FOUR Team, College of Pharmacy, Dongguk University-Seoul, Dongguk-ro-32, Ilsan-Donggu, Goyang, 10326, KoreaTel +82-31-961-5217Fax +82-31-961-5206Email hkhan@dongguk.eduAbstract: Probiotics have demonstrated their high potential to treat and/or prevent various diseases including neurodegenerative disorders, cancers, cardiovascular diseases, and inflammatory diseases. Probiotics are also effective against multidrug-resistant pathogens and help maintain a balanced gut microbiota ecosystem. Accordingly, the global market of probiotics is growing rapidly, and research efforts to develop probiotics into therapeutic adjuvants are gaining momentum. However, because probiotics are living microorganisms, many biological and biopharmaceutical barriers limit their clinical application. Probiotics may lose their activity in the harsh gastric conditions of the stomach or in the presence of bile salts. Moreover, they easily lose their viability under thermal or oxidative stress during their preparation and storage. Therefore, stable formulations of probiotics are required to overcome the various physicochemical, biopharmaceutical, and biological barriers and to maximize their therapeutic effectiveness and clinical applicability. This review provides an overview of the pharmaceutical applications of probiotics and covers recent formulation approaches to optimize the delivery of probiotics with particular emphasis on various dosage forms and formulation technologies.Keywords: probiotic, therapeutic adjuvant, formulation, drug delivery system, gut microbiota

Carbon dioxide concentrations in soil both reflect and influence soil biological activity and C flux to the atmosphere. We hypothesized that erosion affects C[O.sub.2] concentration and C flux from the soil surface because of its effects on soil temperature and water regimes. The soil air concentrations of C[O.sub.2] and corresponding temperature and water contents were monitored on slight (SLI), moderate (MOD), severe (SEV), and depositional (DEP) phases at 2-wk intervals between May 1996 and June 1997. The ambient soil C[O.sub.2] concentration and C[O.sub.2]-C flux were determined using gas chromatograph analyses. Seasonal patterns in soil air C[O.sub.2] concentrations (ranging from a winter low of 0.56 mL [L.sup.-1] to a summer high of 20.90 mL [L.sup.-1]) predominated over more subtle differences (20-80% variation) due to erosion phase effects. Significantly greater (by 12-37%) C[O.sub.2] concentrations for SEV and MOD phases over SLI and DEP were observed mainly during the summer. The effects of the erosion phase on soil C[O.sub.2] concentrations appeared to be indirect through its impacts primarily on soil temperature and, presumably, soil biological activity. Soil air C[O.sub.2] concentrations were significantly correlated with soil temperature ([R.sup.2] = 0.61) and C[O.sub.2]-C ([R.sup.2] = 0.65) flux from the soil surface but not with soil water content. Both linear and second-order polynomial regression equations using soil temperature predicted soil C[O.sub.2] concentration.

The [CO.sub.2]--C flux from soil is an important part of the global C cycle, whose dependence on erosion is as yet largely unknown. We hypothesized that the magnitude of diurnal and seasonal C flux is related to soil erosion phase and is influenced by soil water and temperature regimes. The [CO.sub.2]--C flux from the surface of a Miamian silt loam soil (fine, mixed, active, mesic Oxyaquic Hapludalf) in central Ohio was monitored using the static chamber method. Gas samples were collected four times daily (at 0900, 1200, 1500 and 1800 h) at [approximately equals] 2-wk intervals between July 1995 and June 1997. The [CO.sub.2] evolved from the soil surface varied significantly among seasons ranging from 0 g C [m.sup.-2] [d.sup.-1] in the winter to [approximately equals] 1.6 g C [m.sup.-2] [d.sup.-1] during the summer. Soil erosion phase had no direct effect on C flux from the soil, although depositional areas had 20 to 25% higher water content than other phases, while severely eroded and depositional areas generally had higher soil temperatures than slightly and moderately eroded phases. Soil C flux exhibited diurnal variations with high values differing from lows by as much as 0.04 g C [m.sup.-2] [h.sup.-1]. Peak flux rates as high as 0.082 g C [m.sup.-2] [h.sup.-1] occurred during the mid afternoon during the spring, summer, and autumn seasons. Soil C flux was significantly correlated with soil temperature ([r.sup.2] = 0.804) and air temperature ([r.sup.2] = 0.806) but not with soil moisture content.