Dietary acid load and risk of diminished ovarian reserve: a case-control study.

BACKGROUND: The epidemiologic evidence on the association between acid load potential of diet and the risk of diminished ovarian reserve (DOR) is scarce. We aim to explore the possible relationship between dietary acid load (DAL), markers of ovarian reserve and DOR risk in a case-control study. METHODS: 370 women (120 women with DOR and 250 women with normal ovarian reserve as controls), matched by age and BMI, were recruited. Dietary intake was obtained using a validated 80-item semi-quantitative food frequency questionnaire (FFQ). The DAL scores including the potential renal acid load (PRAL) and net endogenous acid production (NEAP) were calculated based on nutrients intake. NEAP and PRAL scores were categorized by quartiles based on the distribution of controls. Antral follicle count (AFC), serum antimullerian hormone (AMH) and anthropometric indices were measured. Logistic regression models were used to estimate multivariable odds ratio (OR) of DOR across quartiles of NEAP and PRAL scores. RESULTS: Following increase in PRAL and NEAP scores, serum AMH significantly decreased in women with DOR. Also, AFC count had a significant decrease following increase in PRAL score (P = 0.045). After adjustment for multiple confounding variables, participants in the top quartile of PRAL had increased OR for DOR (OR: 1.26; 95%CI: 1.08-1.42, P = 0.254). CONCLUSION: Diets with high acid-forming potential may negatively affect ovarian reserve in women with DOR. Also, high DAL may increase the risk of DOR. The association between DAL and markers of ovarian reserve should be explored in prospective studies and clinical trials.

A comprehensive interventional program to improve the sexual function of women with endometriosis: a mixed-methods protocol study.

BACKGROUND: Endometriosis is a chronic disease affecting 6-10% of women worldwide. Sexual dysfunction has been reported in a significant percentage of these patients. Thus, the present study will be conducted to design, implement, and determine the effectiveness of an interventional program to improve the sexual function of women with endometriosis. MATERIALS AND METHODS: This mixed-methods study will be carried out in three phases with a sequential exploratory approach. In the first phase (qualitative study) participants will be selected by purposive sampling in Isfahan, Iran. The data will be collected through in-depth interviews and field notes and analyzed using conventional content analysis. The interventional program will be designed in the second phase based on the results of the qualitative study and literature review and using the Delphi method and panel of experts. The interventional program will be implemented at the individual level in the third phase to investigate its effect on improving women's sexual function. This phase includes quasi-experimental research, in which the pre- and post-intervention data will be collected from the intervention and control groups using the FSFI questionnaire and analyzed by descriptive and inferential statistical methods. Ultimately, a suitable interventional program will be presented by combining the data obtained in the qualitative and quantitative phases of the research. CONCLUSION: Conducting the present study, along with the design and implementation of an appropriate, native, and culturally sensitive interventional program, can contribute to improving the sexual function of women with endometriosis and enhancing the quality of sexual relations between couples.

Endometriosis is a chronic disease in women of reproductive age. The negative impact of endometriosis on intimate relationships and sexual function has been reported in a significant number of women with this disease. The results of this study offer a rich source of information for the required interventions to promote the sexual and reproductive health of women with endometriosis. This study is a sequential exploratory (qualitative­quantitative) mixed methods design that consists of three consecutive phases. In this study, following a qualitative approach, the researchers will explain the experiences of women with endometriosis of sexual function and the appropriate strategies to improve the sexual function of these women. In the second phase, the researcher will design an appropriate interventional program for to improving the sexual function of women with endometriosis by using the results of the qualitative phase and literature reviews. The purposed interventional program is designed using the Delphi method and panel of experts and will be finalized for execution. In the third stage, the effectiveness of interventional program on the sexual function of women with endometriosis will be investigated in a quasi-experimental study. Therefore, it is expected that conducting a mixed method study by presenting an interventional culturally sensitive program can contribute to improving the sexual function of women with endometriosis and enhancing the quality of sexual relations between couples.

Challenges of home care: a qualitative study.

BACKGROUND: Despite countless benefits of home care, unfortunately, the variety and quality of services provided by homecare centers are uncertain. This study was conducted to explore of home care challenges. METHODS: The present qualitative study used the content analysis approach. A total of 17 participants, including nurses, managers of home care centers, and patients, were enrolled through purposive sampling. Data were collected using semi-structured interviews and analyzed through Granheim's qualitative content analysis method. RESULTS: In order to explain the challenges of home care, after analyzing the data, 700 primary codes, 15 initial categories, sub-subcategories and two main categories, including 'infrastructural challenges' and 'challenges related to the process of home care services provision' emerged. The main category, "infrastructural challenges", consisted of 4 sub-categories (the challenge of acculturalization of home care services, economic challenges of providing services, challenges related to human resources, and the challenge of policymaking and setting regulations and rules for home care). The second main category, "challenges related to the process of home care services provision", consisted of 2 subcategories: challenges of improving the quality of home care services and the challenge of facilities for service provision. CONCLUSION: In order to promote and improve the quality of home care services, in addition to providing insurance coverage for the services, acculturalization and revising the bylaws, empowering the human resource, enhancing the monitoring of the performance of home care centers, and employing modern technology need to be taken into account.

Development, implementation, and evaluation of neonatal thermoregulation decision support web application.

OBJECTIVES: Thermoregulation is important for all age groups, and in neonates, it is considered a crucial event to adapt to extrauterine life. Therefore, using systems that provide frequent reminders in different ways in the field of thermoregulation can help thermal stability in neonates. The present study aimed to develop, implement, and evaluate a neonatal thermoregulation decision support system (DSS) as a web application. METHODS: The present research was a multi-method study because it included the three phases of development, implementation, and evaluation of the neonatal thermoregulation decision support web application. In the system designing phase, the waterfall model is used. The second and third phases of the study, implementation, and evaluation, were conducted as a quasi-experimental study. RESULTS: The results of this study were presented in two parts: the developed web application, and the results of the evaluation of the web application. The results of the statistical tests revealed that the use of the web application had a positive and significant effect on both the adjustment of the temperature of the incubator (maintaining the neutral temperature) and the maintenance of the temperature of the neonate's body (p = 0.000). CONCLUSIONS: These results indicate that a nurse's sensitization and guidance with a neonatal thermoregulation decision support system can help to effectively neonate thermoregulation and the nurse has brought the temperature care close to the standard care based on the conditions of each neonate.

Synergistic anticancer effects of curcumin and crocin on human colorectal cancer cells.

BACKGROUND: Curcumin, a polyphenol compound derived from the Curcuma longa L, and crocin, a hydrophilic carotenoid from Crocus Sativus Linnaeus, are traditionally used in food preparations in many countries and could act as chemopreventive compounds against several diseases, including cancer. In this study, the synergistic effect of curcumin and crocin was investigated for the first time on inducing apoptosis and suppressing colorectal cancer cells (SW-480 cell line). METHODS AND RESULTS: MTT, Annexin V-FITC/PI, and DAPI staining tests were employed to evaluate cell viability and apoptosis induction, respectively. The combined effect of curcumin and crocin on the expression of genes involved in apoptosis and proliferation was quantified using real-time PCR. The combination therapy effect on cell cycle progression was also evaluated by flow cytometry. Based on the obtained results, curcumin and crocin treatment could cooperatively reduce cell viability and induce apoptosis in SW-480 cells by modulating the expression of Bax, Bcl-2, Caspase-3, Caspase-8, Caspase-9, Jak2, Stat3, and Akt1 genes. Besides, curcumin and crocin were able to synergistically increase the cell cycle arrest at the sub G1 phase, induce autophagy and decrease the clonogenic ability of SW-480 cells. CONCLUSIONS: These results suggested that curcumin and crocin combination could be considered a more effective therapeutic strategy for inhibiting colorectal cancer.

Clinical practice guideline for end-of-life care in patients with cancer: a modified ADAPTE process.

PURPOSE: This study seeks to adapt a guideline for end-of-life care in patients with cancer to be used by healthcare teams. METHODS: This methodological study was conducted by modifying the ADAPTE process and adding to it a qualitative study and consensus ratings by a multidisciplinary panel of experts. A qualitative study was thus performed to identify the end-of-life needs of patients with cancer. Then, the source guidelines and the results of the qualitative study were used to draft the initial version of the guideline, with 85 adaptation recommendations. A multidisciplinary panel of healthcare experts performed the external review of the recommendations based on the four criteria of relatedness, comprehensibility, usefulness, and feasibility and scored them on a scale of 1-9. The mean score of each recommendation was calculated, and the recommendations were classified into three categories: appropriate (mean score of 7-9), uncertain (mean score of 4-6.99), and inappropriate (mean score of 1-3.99). RESULTS: All the recommendations were approved, as they all had a mean score of 7 or higher, and were then categorized into 11 dimensions: communication management; participatory and evidence-based decision-making management; pain management; dyspnea management; nausea and vomiting management; anorexia and cachexia management; constipation management; death rattle management; management of delirium, anxiety, and restlessness; hydration management; and pharmacological considerations. CONCLUSION: The adaptation of the guideline for end-of-life care in patients with cancer in Iran was performed by modifying the ADAPTE process with the participation of multidisciplinary stakeholders and based on the local needs.

Effects of Boswellia species on viral infections with particular attention to SARS-CoV-2.

The emergence of pathogenic viruses is a worldwide frequent cause of diseases and, therefore, the design of treatments for viral infections stands as a significant research topic. Despite many efforts, the production of vaccines is faced with many obstacles and the high rate of viral resistance caused a severe reduction in the efficacy of antiviral drugs. However, the attempt of developing novel natural drugs, as well as the exertion of medicinal plants, may be an applicable solution for the treatment of viral diseases. Boswellia species exhibited a wide range of pharmacological activities in various conditions such as bronchial asthma, rheumatism, and Crohn's illness. Additionally, pharmacological studies reported the observance of practical antiviral activities from different parts of this substance, especially the oleo-gum-resin. Therefore, this work provided an overview on the antiviral properties of Boswellia species and their potential therapeutic effects in the field of COVID-19 pandemic.

Evaluation of wound-healing efficiency of a functional Chitosan/Aloe vera hydrogel on the improvement of re-epithelialization in full thickness wound model of rat.

OBJECTIVE: Chitosan-based hydrogels as wound dressings are expected to improve the efficiency of the wound-healing process. Fabrication of the composite structure of Aloe vera and biopolymeric hydrogels has been demonstrated to promote the wound-healing process through protection against a wide spectrum of microbes, and enhanced cell adhesion and differentiation. Therefore, the present study investigates to development of improved CHO/Aloe hydrogel for improving the wound-healing process in an animal model. MATERIALS AND METHODS: CHO hydrogel with Aloe was prepared, and its properties were evaluated in terms of viscosity, antibacterial activity, and ints In-vivo wound-healing efficiency in full-thickness wounds of rat models. Physical examination of wound-healing efficiency of CHO/Aleo hydrogel was evaluated by analyzing total wound closure, recovery percentage, and the epiderm thickness of wounds. Histological evaluation was performed using hematoxylin and eosin staining to evaluate the re-epithelialization, inflammatory response, granulation tissue formation, and fibrotic tissue formation. RESULTS: The results showed a significantly higher wound-healing rate of the CHO/Aleo group compared to other groups at 3,7,14 days (p < 0.05). After 14 days of treatment, the best healing effect was observed in the CHO/Aleo gel with the highest tissue tension compared with other groups (p < 0.05). Histological findings indicated a significant difference in inflammatory response between control and treatment groups after three days of treatment (p < 0.05). Epidermal thickness was also significantly thicker in the CHO/Aleo gel group than others (p < 0.05). CONCLUSION: The present study an improved the effective topical drug-delivery system by CHO/Aloe hydrogel with the potential to reduce inflammation over time, allowing the body to recover more quickly and better re-epithelialization for improving the wound-healing procedures.

Comparison of the Number of Spindle Cells in Peritoneal Washings between Laparoscopic Myomectomy with Morcellation and Open Myomectomy without Morcellation.

STUDY OBJECTIVE: This study evaluated peritoneal washings for the detection of spindle cells (SCs) in laparoscopic and open myomectomies. DESIGN: Prospective, nonrandomized clinical trial. SETTING: An academic tertiary referral center. PATIENTS: Women suspected of having benign uterine myoma undergoing laparoscopic or open myomectomy from October 2016 to April 2018. INTERVENTIONS: Washing of the peritoneal cavity to detect SCs was performed twice during the laparoscopic myomectomy. The first washing was after the closure of the myometrial incision and before morcellation. The second one was performed after morcellation. The procedure was also performed once during the open myomectomy, after the completion of the myomectomy and the closure of the incision. After a peritoneal washing with 200 mL normal saline, 30 mL liquid was collected and sent to the laboratory for SC detection. Surgical parameters such as operating time, mean change in serum hemoglobin level, complications, length of hospital stay, and readmission were compared between the 2 groups. MEASUREMENTS AND MAIN RESULTS: A total of 150 participants were included in the analysis: 78 in the laparoscopic group and 72 in the open myomectomy group. After morcellation, the incidence of SCs was 2.6% (n = 2) and 6.9% (n = 5) in the laparoscopic and open myomectomy groups, respectively (p = .204). CONCLUSION: SCs were observed in both the laparoscopic and open myomectomy groups. Thus, morcellation alone could not be the cause for SC dissemination, which might also be triggered by the manipulation of myoma(s).

Efficacy and safety of tipepidine as adjunctive therapy in major depressive disorder: A randomized, double-blind, placebo-controlled clinical trial.

AIM: Tipepidine, a synthetic, non-opioid expectorant, has been shown to improve depressive-like behavior in animal models of depression. In this study, we assessed the efficacy and tolerability of tipepidine combination therapy with citalopram in treatment of major depressive disorder (MDD). METHODS: In a randomized, double-blinded, placebo-controlled clinical trial, 62 patients with MDD were assigned into two parallel groups to receive citalopram (up to 40 mg/day) plus placebo or citalopram plus tipepidine (30 mg twice daily) for 6 weeks. Participants were assessed with the Hamilton Rating Scale for Depression (HAM-D) at baseline and Weeks 2, 4, and 6. RESULTS: Fifty-six patients completed the trial. The tipepidine group showed greater improvement in HAM-D scores from baseline to all three study time points (P = 0.048 for all). The remission and response-to-treatment rates were significantly higher in the tipepidine group (53.6% and 100%) compared to the placebo group (25.0% and 75%) at the study end-point (P = 0.029 and 0.005, respectively). The remission and response times in patients in the tipepidine group were also shorter compared with the placebo group (log-rank P = 0.020 and 0.004). There was no significant difference between the two groups in baseline parameters or frequency of side-effects. CONCLUSION: Tipepidine combination therapy with citalopram can effectively improve symptoms of patients with MDD in a shorter period of treatment. However, further studies with larger sample sizes and longer follow-up treatment are needed to confirm our findings.

Advanced Hydrogels as Exosome Delivery Systems for Osteogenic Differentiation of MSCs: Application in Bone Regeneration.

Hydrogels are known as water-swollen networks formed from naturally derived or synthetic polymers. They have a high potential for medical applications and play a crucial role in tissue repair and remodeling. MSC-derived exosomes are considered to be new entities for cell-free treatment in different human diseases. Recent progress in cell-free bone tissue engineering via combining exosomes obtained from human mesenchymal stem cells (MSCs) with hydrogel scaffolds has resulted in improvement of the methodologies in bone tissue engineering. Our research has been actively focused on application of biotechnological methods for improving osteogenesis and bone healing. The following text presents a concise review of the methodologies of fabrication and preparation of hydrogels that includes the exosome loading properties of hydrogels for bone regenerative applications.

Effect of alginate coating enriched with Shirazi thyme essential oil on quality of the fresh pistachio (Pistacia vera L.).

In this study, different concentrations of alginate (0%, 1% and 1.5% w/v) enriched with various concentrations of Shirazi thyme (Zataria multiflora Boiss) essential oil (0%, 0.3% and 0.5% w/v), were examined on postharvest characteristics of the fresh pistachio. The measurements (including total phenolic compounds, antioxidant capacity, free fatty acid, peroxide value, aerobic mesophilic bacteria, mold and yeast, saturated and unsaturated fatty acids) were performed after 0, 13, 26 and 39 days during storage (3 ± 1 °C, 80 ± 5% RH). The results showed that alginate edible coating enriched with thyme's essential oil (EO), contributed to the maintenance of higher values of phenolic content and antioxidant activity in comparison with the control. Edible coating treatment of enriched alginate with thyme oil reduced mold and yeast growth compared to the control and the alginate without thyme oil. Peroxide value and free fatty acid content were significantly lower in fruits treated with alginate-thyme in comparison with the control. All fruits which had been treated with alginate-thyme EO showed lower changes in saturated and unsaturated fatty acids after 39 days of storage, and fruits coated with combination of 1% alginate and 0.3% EO showed the highest content of palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid and linolenic acid, compared with other treatments.

PEG-PLA nanoparticles decorated with small-molecule PSMA ligand for targeted delivery of galbanic acid and docetaxel to prostate cancer cells.

Prostate cancer (PCa) is one of the most prevalent non-drug delivery system cutaneous malignancies. Undoubtedly, introducing novel treatment options to achieve higher therapeutic index will be worthwhile. In this study, we report for the first time, a novel targeted self-assembled based on PEG-PLA nanoparticles (PEG-PLA NPs) containing galbanic acid (GBA) and docetaxel, which was targeted using ((S)-2-(3-((S)-5-amino-1-carboxypentyl) ureido) pentanedioic acid (ACUPA), a small molecule inhibitor targeting prostate-specific membrane antigen (PSMA), in prostate cancer cell line. The prepared NPs were characterized by different analytical methods. The MTT assay was used to compare the anti-proliferation of drugs-loaded PEG-PLA NPs and ACUPA-PEG-PLA against LNCaP (PSMA+ ) and PC3 (PSMA- ) cells. PEG-PLA NPs with an average size of 130-140 nm had an enhanced release of GBA and docetaxel at pH 5.5 compared with pH 7.5. Spectrofluorometric analysis suggested that ACUPA-modified PEG-PLA could effectively enhance the drug uptake in PSMA+ prostate cancer cells. Cytotoxicity studies showed that the targeted NPs loaded with different concentrations of GBA and fixed concentration of docetaxel (4 nM) have shown higher toxicity (IC50 30 ± 3 µM) than both free GBA (80 ± 4.5 µM) and nontargeted NPs (IC50 40 ± 4.6 µM) in LNCaP cells. Collectively, these findings suggest that ACUPA-conjugated PEG-PLA nanosystem containing GBA and docetaxel is a viable delivery carrier for various cancer-targeting PSMA that suffer from short circulation half-life and limited therapeutic efficacy.

Aptamer-conjugated PLGA nanoparticles for delivery and imaging of cancer therapeutic drugs.

Most problems associated with chemotherapeutic agents involve non-specific cytotoxicity, low intratumoral accumulation and drug resistance. Targeted drug delivery systems (TDDS) based on nanoparticles (NPs) are a new strategy for better therapeutic efficiency, along with reduction of side effects commonly seen with cancer drugs. Poly (lactic-co-glycolic acid) (PLGA), as one of the furthest developed synthetic polymer, has gained significant attention because of excellent properties-including biodegradability and biocompatibility, controlled release of drug, protection of drug or gene from decomposition and ability to modify surface with targeting agents for both cancer diagnosis and therapy. Aptamers are single-stranded RNA or DNA that can fold through intramolecular interactions into specific three-dimensional structures to selectively and exclusively bind with interested biomarkers. In this review, we explain the latest developments regarding the application of aptamer-decorated PLGA NPs in delivery of therapeutic agents or cancer-related genes into cancer cells. Additionally, we discuss the most recent efforts in the field of aptamer-grafted PLGA-based NPs as theranostics and stimuli-responsive agents.

The quality of guidelines on the end-of-life care: a systematic quality appraisal using AGREE II instrument.

BACKGROUND: Guidelines are intended to facilitate knowledge translation and evidence-based clinical decision-making, but they vary in methodological rigor and quality. The present study was conducted to assess the quality of guidelines available on end-of-life care in patients with cancer using AGREE II. METHODS: A comprehensive search was carried out in EMBASE (Excerpta Medica Database), MEDLINE/PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and gray literature sources until December 2016. The quality of the guidelines was assessed independently by five appraisers using the Appraisal of Guidelines for Research and Evaluation, 2nd edition (AGREE II). To promote consistency with available studies using AGREE II and identify high-quality guidelines, the AGREE II scores were also categorized as "Strongly recommended," "Recommended with modifications," or "Not recommended." RESULTS: A total of 8 guidelines were included in this study. Five of the guidelines were developed based on evidence and two by consensus and one provided no information about its method of development. The highest mean score (82.77%) pertained to "Clarity of presentation" and the lowest to "Editorial independence" (44.80%). Based on the AGREE II results, three guidelines were "Strongly recommended," four were "Recommended with modifications," and one was "Not recommended." CONCLUSION: Despite the variations in the quality and strength of the recommendations, a number of guidelines are currently available on end-of-life care. Health team members should be aware of this variability.

Recent advances in neurogenic and neuroprotective effects of curcumin through the induction of neural stem cells.

Curcumin is extensively used in the prevention and treatment of various diseases. Recently, growing attention has been paid to the use of curcumin as a neurogenic and neuroprotective agent. This review study is aimed to collect and categorize the recent findings regarding the effects of curcumin on various neurological diseases through the induction of neural stem cell proliferation and differentiation. In addition, we have discussed the molecular mechanisms modulated by curcumin that contribute to this efficacy and have summarized the recent advancements in the novel delivery strategies used to improve the induction of neural stem cells by curcumin.

Formulation and evaluation of anticancer and antiangiogenesis efficiency of PLA-PEG nanoparticles loaded with galbanic acid in C26 colon carcinoma, in vitro and in vivo.

Galbanic acid (GBA) is an active sesquiterpene coumarin derivative, with various medicinal benefits, including anticancer properties. However, the low solubility of GBA is the main limitation of its clinical applications. In this study, we used a nanosystem based on poly (D, l-lactide)-polyethylene glycol (PLA-PEG), for the delivery of GBA to C26 colon carcinoma cells. The physicochemical characteristics of nanoparticles (NPs) prepared by the emulsification-evaporation method were evaluated. MTT assay was used to compare the anticell proliferation of GBA and PLA-PEG-GBA against C26 cell lines. PLA-PEG-NPs with an average size of about 140 nm had an enhanced release of GBA at a pH of 5.5 compared with a pH of 7.4. Cytotoxicity studies showed that the IC 50 of the PLA-PEG-GBA NPs (8 µM) was significantly lower than free GBA (15 µM). In the in vivo study, PLA-PEG-GBA NPs exhibited remarkable efficacy and reduced in vivo toxicity in C26 colon carcinoma tumor-bearing female BALB/c mice. To study the antiangiogenesis effect of the NPs, tumor sections were stained with an anti CD34 antibody. The results show the CD34 (+) vessels were decreased in the GBA and PLA-PEG-GBA treated mice by more than 75% and 90%, respectively. These results suggest that the encapsulation of GBA into the PLA-PEG could potentially be used for the treatment of colorectal cancer.

The immunomodulatory role of probiotics in allergy therapy.

The increased incidence of allergic disorders may be the result of a relative fall in microbial induction in the intestinal immune system during infancy and early childhood. Probiotics have recently been proposed as viable microorganisms for the prevention and treatment of specific allergic diseases. Different mechanisms have been considered for this probiotic property, such as generation of cytokines from activated pro-T-helper type 1 after bacterial contact. However, the effects of its immunomodulatory potential require validation for clinical applications. This review will focus on the currently available data on the benefits of probiotics in allergy disease.

Encapsulation of crocetin into poly (lactic-co-glycolic acid) nanoparticles overcomes drug resistance in human ovarian cisplatin-resistant carcinoma cell line (A2780-RCIS).

Nanoparticles and herbal medicines have gained considerable attention in overcoming multidrug resistance through different mechanisms. In this study, the effects of poly (Lactic-co-glycolic acid)-crocetin nanoparticles (PLGA-Crt NPs) on MRP1 and MRP2 activity in a human ovarian cisplatin-resistant carcinoma cell line (A2780-RCIS) and its parental form (A2780) were evaluated. PLGA-Crt NPs were formulated and then characterized. The cytotoxic effect of Crt, PLGA-Crt NPs, and empty PLGA NPs was assessed using MTT test in A2780 and A2780-RCIS cells. The effect of PLGA-Crt NPs on MRP1 and MRP2 mRNA expression was evaluated by Real-Time qRT-PCR. The impact of PLGA-Crt NPs on the functioning of MRP transporters was assessed by the doxorubicin efflux assay. The particle size, entrapment efficiency (EE) and loading capacity (LC) of PLGA-Crt NPs were obtained about 239.8 ± 9 nm, 79 ± 3% and 4.9 ± 0.2%, respectively. The PLGA-Crt NPs IC50 values were obtained 104 ± 3 µM and 96 ± 2 µM in A2780 and A2780-RCIS cell lines, respectively. The Real-time RT-PCR results demonstrated the inhibition of mRNA expression of MRP2 in all studied concentrations (up to 67 ± 8% at 100 µM) in A2780-RCIS cells. PLGA-Crt NPs showed more indirect efflux inhibition (up to 70 ± 5%) compared to direct inhibition (up to 49 ± 5%). The encapsulation of crocetin into PLGA NPs can increase its inhibitory effects on drug resistance by downregulating MRP2 transporters.

Co-delivery of doxorubicin and TRAIL plasmid by modified PAMAM dendrimer in colon cancer cells, in vitro and in vivo evaluation.

One strategy for cancer treatment is combination therapy using nanoparticles (NPs), which has resulted in enhanced anti-cancer effects and reduced cytotoxicity of therapeutic agents. Polyamidoamine dendrimer (PAMAM) has attracted considerable attention because of its potential applications ranging from drug delivery to molecular encapsulation and gene therapy. In this study, PAMAM G5 modified with cholesteryl chloroformate and alkyl-PEG was applied for co-delivery of doxorubicin (DOX) and plasmid encoding TRAIL into colon cancer cells, in vitro and in vivo. The results showed DOX was efficiently encapsulated in modified carrier (M-PAMAM) with loading level about 90%, and the resulting DOX-loaded M-PAMAM complexed with TRAIL plasmid showed much stronger antitumor effect than M-PAMAM containing DOX or TRAIL plasmid. On the other hand, the obtained results demonstrated that the treatment of mice bearing C26 colon carcinoma with this developed co-delivery system significantly decreased tumor growth rate. Thus, this modified PAMAM G5 can be considered as a potential carrier for co-delivery of drug and gene in cancer therapy.