Oral metronomic therapy of pancreatic cancer with gemcitabine and paclitaxel co-loaded in lecithin-based Self-Nanoemulsifying preconcentrate (LBSNEP).

This study aimed to evaluate gemcitabine (GEM)/paclitaxel (PTX) co-loaded into a lecithin-based self-nanoemulsifying preconcentrate (LBSNEP) orally administered in a metronomic therapeutic manner against pancreatic cancer. LBSNEP was developed and evaluated, composed of Caproyl 90, Tween80, lecithin, TPGS, and propyl glycol at a ratio of 20:20:30:5:25, resulting in a droplet diameter of approximately 180 nm. Cell viability studies on MIA PaCa-2 demonstrated a synergetic effect at a proportion of 1:2 between PTX and GEM. Additionally, LBSNEP and baicalein (BAI) were demonstrated to prevent GEM from being deaminated by cytidine deaminase. The combination of GEM, PTX, and BAI in the LBSNEP showed good dissolution in simulated gastric fluid. The pharmacokinetic study conducted on rats showed that co-administration of GEM, PTX, and BAI in the LBSNEP enhanced the respective relative oral bioavailability levels of GEM and PTX by 1.5- and 2-fold, respectively, compared to the solution group. The tumor inhibition study was conducted with metronomic therapy at a low daily dose compared to conventional therapy at a higher dose every 3 days. Results indicated that oral metronomic delivery of GEM/PTX/BAI LBSNEP could inhibit tumor growth during administration phase, and that there were similar tumor volumes compared to traditional chemotherapy at day 28 even if the dose of metronomic chemotherapy was 2.2-fold less than that of the latter. In conclusion, a self-nanoemulsifying drug-delivery system for the oral delivery of GEM, PTX, and BAI in a metronomic manner enhanced the therapeutic effect on pancreatic cancer, providing an alternative option for chemotherapy.

Synergistic Combination of Irinotecan and Rapamycin Orally Delivered by Nanoemulsion for Enhancing Therapeutic Efficacy of Pancreatic Cancer.

In recent years, combining different types of therapy has emerged as an advanced strategy for cancer treatment. In these combination therapies, oral delivery of anticancer drugs is more convenient and compliant. This study developed an irinotecan/rapamycin-loaded oral lecithin-based self-nanoemulsifying nanoemulsion preconcentrate (LBSNENPir/ra) and evaluated its synergistic combination effects on pancreatic cancer. LBSNENP loaded with irinotecan and rapamycin at a ratio of 1:1 (LBSNENPir10/ra10) had a better drug release profile and smaller particle size (<200 nm) than the drug powder. Moreover, LBSNENPir10/ra10 exhibited a strong synergistic effect (combination index [CI] < 1.0) in cell viability and combination effect studies. In the tumor inhibition study, the antitumor activity of LBSNENPir10/ra10/sily20 against MIA PaCa-2 (a human pancreatic cancer cell line) was significantly increased compared with the other groups. When administered with rapamycin and silymarin, the area under the curve and the maximum concentration of irinotecan significantly improved compared with the control. We successfully developed an irinotecan/rapamycin-loaded oral self-nanoemulsifying nanoemulsion system to achieve treatment efficacy for pancreatic cancer.

Carfilzomib and Paclitaxel Co-Loaded Protein Nanoparticles an Effective Therapy Against Pancreatic Adenocarcinomas.

PURPOSE: Therapeutic efficacy of pancreatic adenocarcinomas (PACs) with combined therapy of carfilzomib (CFZ) and paclitaxel (PTX) co-loaded in human serum albumin (HSA) nanoparticles (NPs) was examined. METHODS: CFZ and PTX were encapsulated individually or combined into HSA NPs by a simple reverse self-assembly method developed to achieve an optimal combination ratio for synergistic therapy. CFZ or/and PTX loaded HSA nanoparticles were physically characterized and the evaluation of combination index, drug release, pharmacokinetic, anti-tumor, and biodistribution studies were conducted. RESULTS: All resultant drug-loaded HSA NPs were spherical with a particle size of <150 nm and a zeta potential of -21.1~-23.0 mV. Drug loading rates and entrapment efficiencies were 9.1%~10.1% and 90.7%~97.1%, respectively. CFZ and PTX demonstrated synergistic effects in an MIA PaCa-2 cytotoxicity at a 1:2 ratio (CI50 were 0.01~0.25). In vitro dissolution revealed that the CFZ/PTX ratio released from the co-loaded HSA NPs (CFZ/PTX/HSA NPs) was about 1.77~2.08, which conformed to the designated loaded ratio. In vivo evaluation showed that the combined therapy of CFZ and PTX at a 1:2 ratio co-loaded in HSA NPs (CFZ/PTX/HSA NPs) demonstrated optimal synergistic improvement of the growth inhibition of MIA PaCa-2 cells with less systematic toxicity, even though the pharmacokinetic profiles observed did not show obvious beneficial and their biodistributions in tumors were found to be smaller. CONCLUSION: The one-pot reverse assembly method developed was environmentally friendly and capable of co-loading an optimal combination ratio of two chemodrugs into HSA NPs for synergistic therapy.

Evidenced-based practice of decision-making process in oncofertility care among registered nurses: A qualitative study.

AIM: The purpose of our study was to construct the context of the nursing action/role in oncofertility care. DESIGN: Qualitative research. METHODS: We applied grounded theory to guide the qualitative study. Data were collected through in-depth interviews with 12 nurses in Taipei. The data were collected from August 2018 to February 2019. RESULTS: The core theme that described the role of nurses' decision-making in oncofertility care focused on understanding oncofertility from the self to the other. Care roles or actions in oncofertility that involved the process of psychological cognition were divided into four dimensions: perceiving the patient's changes and needs, triggering the self's emotions, empathizing with patient's situations and introspective care roles. Nurses who had experienced the phase of empathizing with the patient's situations developed more diverse roles and had positive actions toward oncofertility care. Based on the psychological changes for oncofertility decision-making process, implementing contextual training in oncofertility could help nurses create more positive actions in oncofertility care.

Low-fluence laser-facilitated platelet-rich plasma permeation for treating MRSA-infected wound and photoaging of the skin.

Platelet-rich plasma (PRP) is rich in cytokines and growth factors and is a novel approach for tissue regeneration. It can be used for skin rejuvenation but the large molecular size of the actives limits its topical application. In this study, low-fluence laser-facilitated PRP was delivered to evaluate its effect on absorption through the skin, infection-induced wound, and photoaging. The PRP permeation enhancement was compared for two ablative lasers: fractional (CO2) laser and fully-ablative (Er:YAG) laser. In the Franz cell experiment, pig skin was treated with lasers with superficial ablation followed by the application of recombinant cytokines, growth factors, or PRP. The transport of interferon (IFN)-γ and tumor necrosis factor (TNF)-α was negligible in intact skin and stratum corneum (SC)-stripped skin. Both lasers significantly elevated skin deposition of IFN-γ and TNF-α from PRP, and fully-ablative laser showed a higher penetration enhancement. A similar tendency was found for vascular endothelial growth factor and epidermal growth factor. Er:YAG laser-exposed skin displayed 1.8- and 3.9-fold higher skin deposition of platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-ß1 from PRP, respectively. According to the confocal images, both laser interventions led to an extensive and deep distribution of IFN-γ and PDGF-BB in the skin. In the in vivo methicillin-resistant Staphylococcus aureus (MRSA) infection model, CO2 laser- and Er:YAG laser-assisted PRP delivery reduced bacterial load from 1.8 × 106 to 5.9 × 105 and 1.4 × 104 colony-forming units, respectively. The open wound induced by MRSA was closed by the laser-assisted PRP penetration. In the mouse photoaging model, elastin and collagen deposition were fully restored by combined PRP and full-ablative laser but not by PRP alone and PRP combined with fractional laser. Laser-facilitated PRP delivery even with a low fluence setting can be considered a promising strategy for treating some dermatological disorders.

Idiopathic calcinosis cutis in a child: chemical composition of the calcified deposits.

Idiopathic calcinosis cutis (CC) is a rare disease in a child. The chemical composition of the calcified deposits in idiopathic CC was first qualitatively and quantitatively examined using vibrational microspectroscopy via spectral diagnosis. The combined application of the Fourier transform infrared (FT-IR) and Raman microscopic techniques was used to detect and identify the nature of the components of the calcified deposits in idiopathic CC and to compare the results with histopathological findings. Two major components of type B carbonated apatite and ß-carotene interspersing subcutaneous tissue were clearly evidenced to make up the calcified deposits in idiopathic CC in our pediatric patient. Moreover, the calcified deposits of idiopathic CC contained a relatively larger amount of type B carbonated apatite and a smaller amount of type A carbonated apatite than the calcified deposits analyzed in dystrophic CC. This is the first report on the chemical composition of calcified deposits in idiopathic CC established by spectral analysis. The combination of FT-IR and Raman microscopic techniques was very useful for simultaneous assessment of the intact components of the calcified deposits in idiopathic CC.

Preliminary feasibility study of FTIR microscopic mapping system for the rapid detection of the composited components of prostatic calculi.

Awareness of the chemical composition of prostatic calculi is of great importance for pathogenesis of prostatic lithiasis, the feasibility of FTIR microspectroscopic mapping system used for rapidly screening and detecting the real composited components of prostatic calculi in a short time was initially evaluated. Prostatic calculi were retrieved during transurethral resection of the prostate from nine patients diagnosed having benign prostatic hyperplasia with lower urinary tract symptoms. The level of serum prostatic-specific antigen was within 0-12.63 ng/ml. The calculi samples were examined and compared using FTIR microspectroscopic mapping system, or the traditional FTIR and Raman microspectroscopies. The traditional FTIR microspectroscopic results indicate that nine calculi samples mainly consisted of carbonated HA (hydroxyapatite), but calcium oxalate (undifferentiated) might be also detected in some samples. However, Raman spectral results could detect three components, HA, COM (calcium oxalate monohydrate) or COD (calcium oxalate dihydrate) separated in nine samples. Different compositions in the prostatic calculi were obtained by both spectroscopic detections with manual single-point random analysis implying that both manually traditional methods were failed to provide the real chemical composition of the prostatic calculi in a short time. The FTIR microscopic mapping system via point-by-point mapping analysis evidenced that it could rapidly detect all the complicated components distributed within the prostatic calculi rather than uncertain components detected by traditional FTIR or Raman microspectroscopy. More studies should be carried out in future. This preliminary result suggests that the FTIR mapping better characterizes the stone composition over single-point FTIR and Raman microscopic analysis in prostatic calculi.

Spectral analysis and comparison of mineral deposits forming in opacified intraocular lens and senile cataractous lens.

This preliminary report was attempted to compare the chemical components of mineral deposits on the surfaces of an opacified intraocular lens (IOL) and a calcified senile cataractous lens (SCL) by vibrational spectral diagnosis. An opacified intraocular lens (IOL) was obtained from a 65-year-old male patient who had a significant decrease in visual acuity 2-years after an ocular IOL implantation. Another SCL with grayish white calcified plaque on the subcapsular cortex was isolated from a 79-year-old male patient with complicated cataract after cataract surgery. Optical light microscope was used to observe both samples and gross pictures were taken. Fourier transform infrared (FT-IR) and Raman microspectroscopic techniques were employed to analyze the calcified deposits. The curve-fitting algorithm using the Gaussian function was also used to quantitatively estimate the chemical components in each deposit. The preliminary results of spectral diagnosis indicate that the opacified IOL mainly consisted of the poorly crystalline, immature non-stoichiometric hydroxyapatite (HA) with higher content of type B carbonated apatites. However, the calcified plaque deposited on the SCL was comprised of a mature crystalline stoichiometric HA having higher contents of type A and type B carbonate apatites. More case studies should be examined in future.

Spectral diagnosis and analysis of a superior vesical artery calcification.

A case of urinary vessel calcification was detected incidentally in pelvic cavity of a 59-year-old man by computed tomography. The silver reticulin, actin, and hematoxylin and eosin stains were applied to diagnose the feature of vessel and confirmed that the vessel was the vesical artery. To our knowledge, this is the first report to find out the obliteration of superior vesical artery caused by calcified deposit. The calcified deposit in superior vesical artery was qualitatively identified to consist of hydroxyapatite, cholesterol and beta-carotene by Fourier transform infrared and Raman microspectroscopies, in which A-type carbonated apatite was a predominate component.

Identification of monoclinic calcium pyrophosphate dihydrate and hydroxyapatite in human sclera using Raman microspectroscopy.

Raman microspectroscopy was first used to determine the composition of a calcified plaque located at the pterygium-excision site of a 51-year-old female patient's left nasal sclera after surgery. It was unexpectedly found that the Raman spectrum of the calcified sample at 1149, 1108, 1049, 756, 517, 376 and 352/cm was similar to the Raman spectrum of monoclinic form of calcium pyrophosphate dihydrate (CPPD) crystal, but differed from the Raman spectrum of triclinic form of CPPD. An additional peak at 958/cm was also observed in the Raman spectrum of the calcified plaque, which was identical to the characteristic peak at 958/cm of hydroxyapatite (HA). This is the first study to report the spectral biodiagnosis of both monoclinic CPPD and HA co-deposited in the calcified plaque of a patient with sclera dystrophic calcification using Raman microspectroscopy.

Corneal calcification: chemical composition of calcified deposit.

BACKGROUND: The aim of this study was to quickly and quantitatively detect the chemical composition of the calcified deposit on the surface of a surgically excised cornea by using vibrational microspectroscopy. METHODS: Both attenuated total reflection (ATR)/Fourier transform infrared (FTIR) and confocal Raman microspectroscopies were used to evaluate the chemical composition of the excised corneal calcified opaque deposit of a 50-year-old male patient. Hydroxyapatite (HA) was used as a reference. RESULTS: Microscopic observations indicated that a whitish-grayish opaque plaquelike deposit was observed. A peak at 1020 cm(-1) assigned to the stretching vibration of phosphate of the poorly crystalline, immature and nonstoichiometric HA was observed from the IR spectrum of the corneal calcified deposit, as compared with the peak at 1030 cm(-1) of the mature, crystalline and stoichiometric HA reference sample. Higher contents of two IR spectral peaks at 871 cm(-1) due to the type-B carbonated apatite and at 866 cm(-1) corresponded to a labile carbonate were also evidenced in the corneal calcified deposit. The predominate peak at 959 cm(-1) due to the stretching mode of phosphate was also found in the Raman spectrum of corneal calcified deposit. CONCLUSIONS: The corneal calcified deposit was evidenced to contain much poor crystalline and immature HA having higher content of the type-B carbonated apatite within the corneal collagen matrix. The process of corneal calcification still proceeds on the surface of this cornea.

Micro-Raman spectroscopy used to identify and grade human skin pilomatrixoma.

Raman microspectroscopy was applied to analyze the changes in structural conformation and chemical composition of the mass of human skin pilomatrixoma (PMX). The normal skin dermis, collagen type I, and hydroxyapatite (HA) were used as control. The excised specimens from two patients diagnosed as a typical PMX were detected, in which one specimen was a soft mass, but the other was a hard mass with somewhat calcified deposits via histopathological examination. The Raman spectrum of normal skin dermis was found to be similar to the Raman spectrum of collagen type I, confirming that the collagen type I was a predominant component in normal skin dermis. The differences of Raman peak intensity between normal skin dermis and soft or hard PMX mass were obvious at 1,622-1,558, 1,400-1,230, 1,128, 1,000-850, 749, and 509 cm(-1). In particular, the peak at 1,665 cm(-1) assigned to amide I band shifted to 1,655 cm(-1) and the peak at 1,246 cm(-1) corresponding to amide III band was reduced in its intensity in hard PMX mass. The significant changes in collagen content and its structural conformation, the higher content of tryptophan, and disulfide formation in PMX masses were markedly evidenced. In addition, the shoulder and weak peak at 960 cm(-1) assigned to the stretching vibration of PO(4) (3-) of HA also appeared respectively in the Raman spectra of soft and hard PMX masses, suggesting the occurrence of calcification of HA in the PMX tissue, particularly in the hard PMX mass. The result indicates that the micro-Raman spectroscopy may provide a highly sensitive and specific method for identifying normal skin dermis and how it differs in chemical composition from different PMX tissues.

Identification of chemical compositions of skin calcified deposit by vibrational microspectroscopies.

Calcinosis cutis is characterized by the deposition of calcium salts in the subcutaneous tissues. Both Fourier transform infrared (FTIR) and Raman microspectroscopic analysis have been applied to easily get the chemical compositions of the skin calcified deposit (SCD), which was surgically excised from a female patient. This SCD was cut into two parts for histopathological (H&E stain) examination and vibrational microspectroscopic study. The result indicates that the whole SCD in the skin lesion was found to be a well-developed, mature and hard mass. Several FTIR absorption bands at 873, 961 and 1,031 cm(-1) [the stretching modes of carbonate and phosphate of hydroxyapatite (HA)], 1,547 and 1,658 cm(-1) (the amide I and II bands of collagen) were detected in the IR spectrum of SCD. The Raman spectral bands at 1,665 and 1,450 cm(-1) (collagen); 1,519 and 1,156 cm(-1) (beta-carotene); and 1,072 and 958 cm(-1) (HA) were also obtained. To our knowledge, this is the first report using FTIR and Raman microspectroscopies to quickly identify and quantify three predominant components, collagen, beta-carotene and type B carbonated HA, in the SCD of a patient.

Retained antibiotic ophthalmic ointment on an intraocular lens 34 months after sutureless cataract surgery.

PURPOSE: To quickly examine the long-term retained oily-like material on the intraocular lens (IOL) of a sutureless cataract surgical patient. DESIGN: Observational case report. METHODS: Fourier transform infrared (FT-IR) and confocal Raman microspectroscopies were used to identify the deposited materials on explanted IOL. RESULTS: A 70-year-old man underwent a sutureless cataract surgery for his right eye. Garamycin ophthalmic ointment was postoperatively applied on the conjunctival fornix. His vision was improved to 20/25 after surgery but declined gradually to 20/400 half a year later. An oily-like hump on the anterior surface of IOL was found and he underwent IOL exchange after approximately 3 years. The oily-like material was identified by using FT-IR and Raman microspectroscopies to be garamycin ophthalmic ointment. CONCLUSIONS: Both FT-IR and Raman microspectroscopies can easily examine the retained antibiotic ophthalmic ointment on the IOL. Direct access of ophthalmic ointment into ocular anterior chamber through the sutureless incision is a potential risk.

Fourier transform IR attenuated total reflectance spectroscopy studies of cysteine-induced changes in secondary conformations of bovine serum albumin after UV-B irradiation.

Fourier transform IR spectroscopy equipped with attenuated total reflection was used to investigate the cysteine-induced alteration of the protein secondary structure of bovine serum albumin (BSA) in aqueous solution before and after UV-B irradiation. Several amino acids were also studied. The results indicate the unchanged IR spectra of BSA coincubated with amino acids, except cysteine, did not change after 72-h UV-B irradiation. There was no difference in the IR spectrum of the unirradiated BSA coincubated with cysteine. A shoulder at 1620 cm(-1) attributed to the intermolecular beta-sheet structure was observed for the IR spectrum of BSA coincubated with cysteine after 72-h UV-B irradiation. Moreover, the peak intensity at 1303 cm(-1) that is due the alpha-helix structure was reduced, but the peak intensity at 1247 cm(-1) corresponding to beta-sheet structures was increased. Longer UV-B exposure for a BSA solution coincubated with cysteine changed the BSA solution from clear to viscous to gel form in which a transparent gel and another white gel were simultaneously observed. A gradual IR spectral alteration was found for BSA coincubated with cysteine and subjected to increased UV-B irradiation. The longer UV-B irradiation yielded increased intensity at 1620 cm(-1). The second-derivative IR peaks at 1655, 1631, and 1548 cm(-1) were shifted to 1650, 1620, and 1544 cm(-1), respectively, by the increase of UV-B irradiation, suggesting a progressive transformation from an alpha-helix to an intermolecular beta-sheet structure for BSA coincubated with cysteine. This strongly implies that longer UV-B exposure time for the BSA solution in the presence of cysteine did alter the protein secondary structures of BSA more, thus inducing gel formation by protein aggregation.