A highly selective and sensitive rhodamine B-based chemosensor for Sn4+ in water-bearing and biomaging and biosensing in zebrafish.

A novel colorimetric-fluorescent dual-mode chemosensor (JT5) based on rhodamine B has been produced for monitoring Sn4+ in the DMSO/H2O (4:1, v/v) medium. It has high sensitivity, a low detection limit, a short response time (1 s) and high stability, and can still be maintained after two weeks with the red dual fluorescence/ colorimetric response. Enhancement of red fluorescence (591 nm) and red colorimetric (567 nm) response of JT5 by Sn4+ addition. The electrostatic potential of the sensor JT5 molecule was simulated to speculate on the sensing mechanism, and the IR, mass spectrometry and 1H NMR titration were utilized to further demonstrate that JT5 was coordinated to Sn4+ with a 1:1 type, the rhodamine spironolactam ring of JT5 opens up to form a penta-membered ring with Sn4+, meanwhile, its system may have chelation enhanced fluorescence (CHEF) effect. In addition, theoretical calculations were carried out to give the energy gaps of JT5 and [JT5 + Sn4+] as well as to simulate the electronic properties of the maximal absorption peaks. Notably, the sensor JT5 was successfully applied to monitoring Sn4+ in zebrafish, and the JT5-loaded filter paper provided a solid-state platform for detecting Sn4+ by both naked eye and fluorescent methods. In summary, this work contributes to monitoring Sn4+ in organisms and solid-state materials and promotes understanding of Sn4+ functions in biological systems, environments, and solid-state materials.

Ratiometric emission of Tb(III)-functionalized Cd-based layered MOFs for portable visual detection of trace amounts of diquat in apples, potatoes and corn.

Diquat (DQ) is a typical bipyridine herbicide widely used to control weeds in fields and orchards. The severe toxicity of diquat poses a serious threat to the environment and human health. Metal-organic frameworks (MOFs) have received widespread attention due to their unique physical and chemical properties and applications in the detection of toxic and harmful substances. In this work, a two-dimensional (2D) Tb(III) functionalized MOF Tb(III)@1 (1 = [Cd(HTATB)(bimb)]n·H2O (Cd-MOF), H3TATB = 4,4',4″-triazine-2,4,6-tribenzoicacid, bimb = 1,4-bis((1H-imidazol-1-yl)methyl)benzene) has been prepared and characterized. Tb(III)@1 has excellent optical properties and high water and chemical stability. After the Tb(III) is fixed by the uncoordinated -COO- in the 1 framework, Tb(III)@1 emits the typical green fluorescence of the lanthanide ion Tb(III) through the "antenna effect". It is worth noting that Tb(III)@1 can be used as a dual emission fluorescence chemical sensor for the ratio fluorescence detection of pesticide DQ, exhibiting a relatively low detection limit of 0.06 nM and a wide detection range of 0-50 nM. After the addition of DQ, a rapid color change of Tb(III)@1 fluorescence from green to blue was observed due to the combined effects of IFE, FRET and dynamic quenching. Therefore, a simple test paper box has been designed for direct on-site determination of pesticide DQ. In addition, the developed sensor has been successfully applied to the detection of DQ in real samples (fruits a Yin-Xia Sun and Bo-Tao Ji contributed equally to this work and should be considered co-first authors.nd vegetables) with satisfactory results. The results indicate that the probe developed in this study has broad application prospects in both real sample detection and actual on-site testing.

Erratum: Author correction to 'Amino-functionalized poloxamer 407 with both mucoadhesive and thermosensitive properties: Preparation, characterization and application in vaginal drug delivery system' [Acta Pharm Sin B 7 (2017) 593-602].

[This corrects the article DOI: 10.1016/j.apsb.2017.03.002.].

Correction: Ci et al. Enhanced Delivery of Imatinib into Vaginal Mucosa via a New Positively Charged Nanocrystal-Loaded in Situ Hydrogel Formulation for Treatment of Cervical Cancer. Pharmaceutics 2019, 11, 15.

In the original publication [...].

Electrospun fibers with blank surface and inner drug gradient for improving sustained release.

New engineering methods and advanced strategies are highly desired for creating novel drug sustained release nanomaterials. In this study, a trilayer concentric spinneret was explored to implement several multifluid electrospinning processes. A trilayer core-shell nanofiber was successfully fabricated, which comprise a drug-free polymeric coating and an inner drug gradient distribution, and then compared with bilayer core-shell and monolithic medicated nanofibers. All the electrospun nanofibers similarly consisted of two components (guest drug acetaminophen and host polymer cellulose acetate) and presented a linear morphology. Due to the secondary interactions within nanofibers, loaded drug with amorphous state was detected, as demonstrated by SEM, DSC, XRD, and FTIR determinations. In vitro and in vivo gavage treatments to rats tests were carried out, the trilayer nanofiber with an elaborate structure design were demonstrated to provide better drug sustained release profile than the bilayer core-shell nanofibers in term of initial burst release, later tail-off release and long sustained release time period. The synergistic mechanism for improving the drug sustained release behaviors is disclosed. By breaking the traditional concepts about the implementation of multifluid electrospinning and the strategy of combining surface properties and inner structural characteristics, the present protocols open a new way for developing material processing methods and generating novel functional nanomaterials.

Erratum: Author correction to 'Amino-functionalized poloxamer 407 with both mucoadhesive and thermosensitive properties: Preparation, characterization and application in vaginal drug delivery system' Acta Pharm Sin B 7 (2017) 593-602

[This corrects the article DOI: 10.1016/j.apsb.2017.03.002.].

Status Quo and Research Progress in Diagnosis and Treatment of Patients With Diabetes Mellitus and Chronic Kidney Disease / 中国医学科学院学报

As the incidence of diabetes mellitus is rapidly increasing worldwide,that of related complications,such as diabetic kidney disease(DKD),also increases,conferring a heavy economic burden on the patients,families,society,and government.Diabetes mellitus complicated with chronic kidney disease(CKD)includes DKD and the CKD caused by other reasons.Because of the insufficient knowledge about CKD,the assessment of diabetes mellitus complicated with CKD remains to be improved.The therapies for diabetes mellitus complicated with CKD focus on reducing the risk factors.In clinical practice,DKD may not be the CKD caused by diabetes.According to clinical criteria,some non-diabetic kidney disease may be misdiagnosed as DKD and not be treated accurately.This review summarizes the status quo and research progress in the assessment,diagnosis,and treatment of diabetes mellitus complicated with CKD and predicts the directions of future research in this field.

Evaluation of Secondary Chemistry due to Disinfection of Indoor Air with Germicidal Ultraviolet Lamps

Air disinfection using Germicidal Ultraviolet light (GUV) has received increasing attention during the COVID-19 pandemic. GUV uses UVC lamps to inactivate microorganisms, but it also initiates photochemistry in air. However, GUVs indoor-air-quality impact has not been investigated in detail. Here, we model the chemistry initiated by GUV at 254 ("GUV254") or 222 nm ("GUV222") in a typical indoor setting for different ventilation levels. Our analysis showed that GUV254, usually installed in the upper room, can significantly photolyze O3, generating OH radicals that oxidize indoor volatile organic compounds (VOCs) into more oxidized VOCs. Secondary organic aerosol (SOA) is also formed as a VOC-oxidation product. GUV254-induced SOA formation is of the order of 0.1-1 g/m3 for the cases studied here. GUV222 (described by some as harmless to humans and thus applicable for the whole room) with the same effective virus-removal rate makes a smaller indoor-air-quality impact at mid-to-high ventilation rates. This is mainly because of the lower UV irradiance needed and also less efficient OH-generating O3 photolysis than GUV254. GUV222 has a higher impact than GUV254 under poor ventilation due to a small but significant photochemical production of O3 at 222 nm, which does not occur with GUV254. SynopsisGermicidal ultraviolet light initiates indoor oxidation chemistry, potentially forming indoor air pollutants. The amount is not negligible and depends on both the wavelength of light and the ventilation level.

Research progress of the mechanism for PD-1 molecule regulating pulmonary fibrosis and its research prospects in silicosis / 公共卫生与预防医学

Programmed death factor-1 (PD-1) is a promising target molecule for clinical tumor immunotherapy in recent years. Recent studies suggest that PD-1 and related signaling pathways (PI3K/AKT, JAK/STAT3, p38MAPK, ERK, etc.) played a key regulatory role in the process of pulmonary fibrosis. Silicosis is a systemic disease caused by inhalation of free silicon dioxide dust, which is mainly characterized by extensive pulmonary nodular fibrosis and seriously endangers the health of patients. Dissecting the role of PD-1 in the pathogenesis of silicosis may be of great significance in the mechanism research and clinical diagnosis and treatment of silicosis. This paper reviews the regulation of PD-1 molecule on related signaling pathways and its role in pulmonary fibrosis, and looks forward to the potential application of these mechanistic studies in silicosis research.

Preparation of oxytocin liposomes modified by cell penetrating peptides and evaluation on brain targeting efficiency via intranasal delivery / 药学学报

The water-soluble polypeptide drug oxytocin was encapsulated in liposomes by reverse-phase evaporation vesicle method to obtain oxytocin loaded liposomes (OT@LPs) which was further modified with cationic cell penetrating peptide—arginine octamer (R8) to get R8 modified oxytocin loaded liposomes (OT@LPs-R8) which showed enhanced mucoadhesive. The brain targeting efficiency was evaluated preliminarily after nasal administration. OT@LPs-R8 showed a round shape with a particle size distribution of 110.2 ± 7.3 nm, a surface potential as high as +18 mV, a drug loading (62.17 ± 1.88) %, an encapsulation rate (5.85 ± 0.72) %, and stood stable in nasal mucus. After nasal administration, it could significantly prolong the retention and enhance the distribution in the brain with no irritation to the nasal mucosa. The animal experiment in line with the regulations of the Department of Laboratory Animal Science of Fudan University on the ethics of animal experiments had been carried out after passing the review of the Animal Ethics Committee of Fudan University. The results showed nasal administration of OT@LPs-R8 could promote oxytocin directly into the brain from the nose which expected to become a new carrier for delivery of oxytocin to the brain.

Research progress of delivery strategies related mucus barrier in mucosal drug delivery / 药学学报

The mucous barrier is a major physiological obstacle that the mucosal drug delivery system needs to deal with. In response to this physiological barrier, many achievements have been made in research of mucosal adhesion and mucus penetration. This review puts emphasis on the progress of the research on new mucosal adhesion strategies such as cationization, sulfhydrylization, maleimide functionalization, lectinization and catechol conjugation; polyethylene glycol (PEG), polyvinyl alcohol (PVA), poly (2-alkyl-2-oxazoline) (POZ), zwitterionic polymers and other mucus-inert materials, strategies to enhance mucus penetration ability such as enzyme functionalization, reducing agent pretreatment and so on. The problems of each strategy are also analyzed and discussed, which can provide some references for clinical transformation.

Effect of Sanjie Xiaoliu Recipe on epithelial mesenchymal transformation of transplanted tumor in breast cancer mice / 中国医师杂志

Objective:To study the effect of Sanjie Xiaoliu Recipe on transplanted tumors in breast cancer mice through in vivo experiments, in order to explore the efficacy and mechanism of Sanjie Xiaoliu Recipe on breast cancer patients. Methods:45 BaL B/c female mice were selected to establish the transplanted tumor model of breast cancer. All the transplanted tumor models of breast cancer mice were randomly divided into five groups: the control group (intragastric administration of normal saline), the low, medium and high dose group of Sanjie Xiaoliu Recipe (intragastric administration of different doses of Sanjie Xiaoliu Decoction), and the paclitaxel group (intraperitoneal injection of paclitaxel). After 24 days of continuous administration, the diet and activities of mice were observed; the body weight, weight and volume changes of transplanted tumor mice were recorded, and the tumor inhibition rate was calculated. Western blot was used to detect the expression of epithelial mesenchymal transformation related proteins (E-cadherin, N-cadherin, Vimentin) in the transplanted tumor tissues of mice in each group.Results:(1) The food intake and activity status of mice treated with Sanjie Xiaoliu Recipe were less affected by the transplanted tumor of breast cancer. (2) The volume and weight of transplanted tumor in the treat groups were smaller than those in the control group (all P<0.01), and the volume of transplanted tumor in the middle dose group of Sanjie Xiaoliu Recipe was smaller than that in the low dose group ( P<0.05). The tumor inhibition rates among the treatment groups were: Sanjie Xiaoliu Recipe medium dose group 52.4%, paclitaxel group 40.3%, Sanjie Xiaoliu Recipe low dose group 39.5%, Sanjie Xiaoliu Recipe high dose group 34.1%. (3) The results of Western blot showed that the expression level of E-cadherin in the transplanted tumor tissue of the treat groups was higher than that in the control group, and the expression levels of N-cadherin and Vimentin were lower than that in the control group, with statistically significant difference (all P<0.05). Conclusions:The Sanjie Xiaoliu Recipe can improve the weakness and reduced consumption of breast cancer mice, which can inhibit the tumor mass growth in mice to a certain extent. Its mechanism may be that Sanjie Xiaoliu Recipe can inhibit the epithelial mesenchymal transformation of breast cancer and the invasion and metastasis of breast cancer.

Indicators for Risk of Airborne Transmission in Shared Indoor Environments and their application to COVID-19 Outbreaks

Some infectious diseases, including COVID-19, can be transmitted via aerosols that are emitted by an infectious person and inhaled by susceptible individuals. Most airborne transmission occurs at close proximity and is effectively reduced by physical distancing, but as time indoors increases, infections occur in those sharing room air despite maintaining distancing. There have been calls for quantified models to estimate the absolute and relative contribution of these different factors to infection risk. We propose two indicators of infection risk for this situation, i.e., relative risk parameter (Hr) and risk parameter (H). They combine the key factors that control airborne disease transmission indoors: virus-containing aerosol generation rate, breathing flow rate, masking and its quality, ventilation and particulate air cleaning rates, number of occupants, and duration of exposure. COVID-19 outbreaks show a clear trend in relation to these factors that is consistent with airborne infection The observed trends of outbreak size (attack rate) vs. H (Hr) allow us to recommend values of these parameters to minimize COVID-19 indoor infection risk. Transmission in typical pre-pandemic indoor spaces is highly sensitive to mitigation efforts. Previous outbreaks of measles, flu, and tuberculosis were assessed along with recently reported COVID-19 outbreaks. Measles outbreaks occur at much lower risk parameter values than COVID-19, while tuberculosis outbreaks are observed at much higher risk parameter values. Since both diseases are accepted as airborne, the fact that COVID-19 is less contagious than measles does not rule out airborne transmission. It is important that future outbreak reports include information on the nature and type of masking, ventilation and particulate-air cleaning rates, number of occupants, and duration of exposure, to allow us to understand the circumstances conducive to airborne transmission of different diseases. SynopsisWe propose two infection risk indicators for indoor spaces and apply them to COVID-19 outbreaks analysis and mitigation.

Clinical characteristics of crystal deposits in joints and tendons in patients with gout / 北京大学学报(医学版)

OBJECTIVE@#To explore the abnormal manifestations and clinical features of patients with gout according to the location of crystal deposits: in articulars or in tendons.@*METHODS@#A total of 105 patients with gout who were continuously treated in the Department of Rheumatology and Immunology of Peking University People's Hospital from June 2019 to December 2019 were selected and their knees, ankles, toes and painful joints and tendons were examined by high-frequency ultrasound. Then we grouped them according to the presence or absence of sodium urate crystals and the location of the crystals, collected their clinical data, and analyzed the clinical characteristics.@*RESULTS@#Among the 105 patients, 25 patients had no crystal deposits in the joints or tendons (as the non-crystal group), 43 patients had intra-articular crystals (as the joint group), and 37 patients had intra-tendon crystals with or without intra-articular crystals (as the tendon group). Among them, the most involved part of sodium urate crystals deposited in the joints was the metatarsophalangeal joint (29 cases, 67.4%), followed by knee joints (10 cases, 23.2%), ankle joints (9 cases, 20.9%). The most involved part of sodium urate crystals deposited in the tendon was the quadriceps tendon (16 cases, 43.2%), followed by the Achilles tendon (13 cases, 35.1%), the patellar tendon (12 cases, 32.4%), and the three heads of brachii tendons (5 cases, 13.5%). The three groups were compared using multi-sample analysis of variance/multi-sample rank sum test. Age, age of first increase in uric acid (UA), serum glucose (Glu) level and C reactive protein (CRP) were all significantly different. After multiple comparisons, compared with the non-crystal group, age, the age of first increase in uric acid, and CRP were significantly higher in the tendon group. There was no significant difference between the non-crystal group and the joint group. There was no significant difference between the tendon group and the joint group.@*CONCLUSION@#In patients with gout, it is common for ultrasound to find crystals deposited in joints or tendons. The most commonly affected parts include the metatarsophalangeal joint, knee joint, ankle joint, quadriceps tendon, Achilles tendon, patellar tendon, and triceps tendon. There were significant differences among the three groups in age, age of first increase in uric acid, CRP and blood glucose, and the proportion of urinary calculi in patients with crystal deposits was significantly higher than those without crystal deposits.

Exhaled CO2 as COVID-19 infection risk proxy for different indoor environments and activities

CO2 is co-exhaled with aerosols containing SARS-CoV-2 by COVID-19 infected people and can be used as a proxy of SARS-CoV-2 concentrations indoors. Indoor CO2 measurements by low-cost sensors hold promise for mass monitoring of indoor aerosol transmission risk for COVID-19 and other respiratory diseases. We derive analytical expressions of CO2-based risk proxies and apply them to various typical indoor environments. The relative infection risk in a given environment scales with excess CO2 level, and thus keeping CO2 as low as feasible in a space allows optimizing the protection provided by ventilation. We show that the CO2 level corresponding to a given absolute infection risk varies by over 2 orders of magnitude for different environments and activities. Although large uncertainties, mainly from virus exhalation rates, are still associated with infection risk estimates, our study provides more specific and practical recommendations for low-cost CO2-based indoor infection risk monitoring. Table of Contents Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC="FIGDIR/small/20191676v2_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@129c22aorg.highwire.dtl.DTLVardef@8a7d07org.highwire.dtl.DTLVardef@165cfforg.highwire.dtl.DTLVardef@339687_HPS_FORMAT_FIGEXP M_FIG C_FIG

Functional Status, Supportive Care Needs, and Health-Related Quality of Life in Advanced Lung Cancer Patients Aged 50 and Older.

OBJECTIVE: This study aimed to examine the levels of functional status, supportive care needs, and health-related quality of life (HRQOL), and their relationships reported by advanced lung cancer patients aged 50 and older. METHODS: A cross-sectional descriptive correlational study was conducted with 103 participants recruited from a cancer center in Singapore. Functional status, supportive care needs, and HRQOL were measured using validated instruments. Descriptive statistics were used to describe the sample profiles. Univariate and multivariate regression analyses were adopted to determine factors that were associated with HRQOL. RESULTS: About 70.9% of participants were dependent in at least one instrumental activities of daily living (IADL). The mean number of unmet needs rated by participants was 9 (range = 0-28). The top three ranked items with moderate-to-severe unmet needs were "not being able to do things you used to do" (28.2%), "fear about cancer spreading" (25.3%), and "lack of energy/tiredness" (25.2%). Higher IADL scores were significantly associated with better HRQOL, whereas higher levels of supportive care needs, particularly in psychological domain significantly predicted poorer HRQOL in most domains. CONCLUSIONS: This study found that poor functional status and unmet supportive care needs are common in advanced lung cancer patients. Psychological needs and functional status are associated with patients' HRQOL. Future interventions incorporating functional assistance and psychological support may increase HRQOL in this population.

Synergistic Antitumor Effects on Drug-Resistant Breast Cancer of Paclitaxel/Lapatinib Composite Nanocrystals.

Drug resistance presents serious difficulties for cancer treatment. A combination of paclitaxel (PTX) and lapatinib (LAPA) shows potentials in multiple drug resistant cancers in the clinic, but it is almost impossible to deliver these two drugs to the tumor at the same time with the best proportion by simple co-administration of the respective current formualtions for their different pharmacokinetic profiles. Here composite nanocrystals of PTX and LAPA (cNC) were designed with a ratio of 2:1 (w/w), which was their intracellular ratio at the best synergistic efficacy on a drug-resistant cancer cell line (MCF-7/ADR). Such cNC were prepared using a bottom-up method to achieve a nearly spherical appearance and a narrow size distribution of 95.1 ± 2.1 nm. For nanocrystal stabilization, Polyethylene glycol (PEG) coating was introduced into the cNC via polydopamine (PDA) coating in order to get a PEGylated composite nanocrystal (cNC@PDA-PEG) with nanoscale size (170.5 ± 1.4 nm), considerable drug loading (PTX: 21.33 ± 1.48%, LAPA: 10.95 ± 1.24%) and good stability for at least 4 days in plasma-containing buffers. Differential scanning calorimeter (DSC) and XRD data both indicated the different crystalline states of the cNC as well as the cNC@PDA-PEG in comparison with bulk drugs. In vitro release data showed that PTX and LAPA were gradually and completely released from cNC@PDA-PEG in 3 days, while drug release from bulk drugs or cNC was only 30%. cNC@PDA-PEG also showed negligible hemolysis in vitro. Cellular uptake experiments in the MCF-7/ADR cell line showed that the nanocrystals entered the cells in a complete form through endocytosis and then released the drug in the cell. cNC@PDA-PEG inhibits the growth of this drug-resistant cell more effectively than the unmodified version (cNC). In summary, PEGylated PTX and LAPA composite nanocrystals showed the potential for treament of drug-resistant tumors by simultaneously delivering two drugs to tumor cells with the best proportion.

Epidemiological and clinical characteristics of novel coronavirus infection in children: Thoughts on the diagnostic criteria of suspected cases / 中国小儿急救医学

Objective:To improve the diagnostic criteria of suspected cases through investigating the epidemiological and clinical manifestations of confirmed cases of novel coronavirus infection in children.Methods:We retrospectively analyzed the epidemiological and clinical manifestations of six children with novel coronavirus infection diagnosed in Chongqing Three Gorges Central Hospital from February 3, 2020 to February 15, 2020.Compared with the diagnostic criteria of suspected cases, we summarized the problems encountering in the application of this standard in clinic and try to put forward suggestions for improvement.Results:Among the six confirmed cases: five males and one female; three from Hubei Province and three from Wanzhou; six cases of clustered onset of the family.Visiting nature: six cases of suspected case, six cases from community or outpatient screening.Three fever cases with/without respiratory symptoms, one of which had diarrhea; all children′s blood routine and lymphocyte counts were within the normal range; chest CT imagings of No.1 and No.5 case showed typical novel coronavirus pneumonia signs, and the other three patients had abnormalities without the characteristics of novel coronavirus pneumonia, and one case was normal.Comparison results: Only No.1 case fully met the diagnostic criteria, and the remaining cases did not meet the diagnostic criteria for early suspected cases.Conclusion:In order to improve the accuracy and practicality of the diagnosis of suspected cases in children, it is recommended to refine and standardize the diagnostic criteria for some suspected cases.

Epidemiological and clinical characteristics of novel coronavirus infection in children: Thoughts on the diagnostic criteria of suspected cases outside Hubei Province / 中国小儿急救医学

Objective@#To improve the diagnostic criteria of suspected cases through investigating the epidemiological and clinical manifestations of confirmed cases of new-type coronavirus infection in children.@*Methods@#We retrospective analyzed the epidemiological and clinical manifestations of 6 children with new coronavirus infection diagnosed in Chongqing Three Gorges Central Hospital from February 3, 2020 to February 15, 2020 . Compared with the diagnostic criteria of suspected cases,we summarized the problems encountered in the application of this standard in clinical work and try to put forward Suggestions for improvement.@*Results@#Among the 6 children with confirmed cases: 5 males and 1 female; 3 from Hubei Province and 3 from Wanzhou ; 6 cases of clustered onset of the family; Visiting nature: 3 cases of suspected case income, 3 cases of community or outpatient screening . Three cases with fever and / or respiratory symptoms, one of which had symptoms of diarrhea; all children's blood routine and lymphocyte counts were within the normal range; chest CT imaging except for cases No. 1 and No. 5 were in line with typical new coronavirus pneumonia signs. In addition, the remaining 3 patients had abnormal imaging but did not have the characteristics of new coronavirus pneumonia, and 1 case was normal. Comparison results:Only case 1 of all cases fully met the diagnostic criteria, and the remaining cases did not meet the diagnostic criteria of early suspected cases.@*Conclusion@#In order to improve the accuracy and practicality of the diagnosis of suspected cases in children, it is recommended to refine and standardize the diagnostic criteria of some suspected cases.

Enhanced Delivery of Imatinib into Vaginal Mucosa via a New Positively Charged Nanocrystal-Loaded in Situ Hydrogel Formulation for Treatment of Cervical Cancer.

The present study was carried out to investigate the potential of cationic functionalization on imatinib nanocrystals to improve the mucoadhesiveness and, thus, delivery to the lesion of cervicovaginal tumors. Amino-group-functionalized imatinib nanocrystals (NC@PDA-NH2) were prepared with near-spheroid shape, nanoscale size distribution, positive zeta potential, and relatively high drug content with the aid of the polydopamine-coating technique. Efficient interaction between NC@PDA-NH2 and mucin was proven by mucin adsorption which was related to the positive zeta-potential value of NC@PDA-NH2 and the change in the size distribution on mixing of NC@PDA-NH2 and mucin. Cellular uptake, growth inhibition, and apoptosis induction in cervicovaginal cancer-related cells demonstrated the superiority of NC@PDA-NH2 over unmodified nanocrystals. For practical intravaginal administration, NC@PDA-NH2 was dispersed in Pluronic F127-based thermosensitive in situ hydrogel, which showed suitable gelation temperature and sustained-release profiles. In comparison with unmodified nanocrystals, NC@PDA-NH2 exhibited extended residence on ex vivo murine vaginal mucosa, prolonged in vivo intravaginal residence, and enhanced inhibition on the growth of murine orthotopic cervicovaginal model tumors indicated by smaller tumor size, longer median survival time, and more intratumor apoptosis with negligible mucosal toxicity. In conclusion, cationic functionalization endowed NC@PDA-NH2 significant mucoadhesiveness and, thus, good potential against cervicovaginal cancer via intravaginal administration.