Current Status and Issues of Collaboration Between Physicians and Pharmacists in Fertility Preservation.

Purpose: This study addresses the critical issue of fertility preservation among young patients with cancer in Japan, recognizing the brief decision-making window and the need for comprehensive support. Pharmacists, well-versed in the side effects of anticancer drugs, can play a vital role in this support process. However, the extent of pharmacists' involvement in fertility preservation remains unclear. We aimed to investigate pharmacists' roles in addressing cancer treatment-induced fertility concerns and their collaboration with physicians, offering insights into enhancing pharmacist participation in fertility preservation. Methods: A survey conducted between April and July 2022 targeted doctors and pharmacists at cancer treatment hospitals, along with pharmacists affiliated with the Japanese Society of Pharmaceutical Health Care and Sciences. Results: Our findings indicated that although pharmacists had limited knowledge about gonadotoxicity and fertility, they expressed readiness to conduct research and provide information when consulted. Approximately 10%-20% of the pharmacists participated in explaining the primary disease at diagnosis. Pharmacists played a more prominent role after establishing chemotherapy regimens, with less involvement in its formulation. Notably, treatment decision case conferences emerged as crucial forums for gathering patient data, confirming treatment plans, and identifying those in need for fertility preservation information. Roughly half of the pharmacists attended these conferences, suggesting a need for increased participation. Conclusion: Enhancing physician-pharmacist collaboration could be pivotal for effective fertility preservation. This requires augmenting the knowledge and awareness of both professions and encouraging greater participation in case conferences to create a conducive environment for addressing this critical aspect of cancer care.

Unravelling the role of HAS2, GREM1, and PTGS2 gene expression in cumulus cells: implications for human oocyte development competency - a systematic review and integrated bioinformatic analysis.

The leading indicator for successful outcomes in in-vitro fertilization (IVF) is the quality of gametes in oocytes and sperm. Thus, advanced research aims to highlight the parameter in assessing these qualities - DNA fragmentation in sperm and oocyte development capacity (ODC) via evaluation of microenvironments involving its maturation process. Regarding oocytes, most evidence reveals the role of cumulus cells as non-invasive methods in assessing their development competency, mainly via gene expression evaluation. Our review aims to consolidate the evidence of GDF-9 derivatives, the HAS2, GREM1, and PTGS2 gene expression in cumulus cells used as ODC markers in relevant publications and tailored to current IVF outcomes. In addition to that, we also added the bioinformatic analysis in our review to strengthen the evidence aiming for a better understanding of the pathways and cluster of the genes of interest - HAS2, GREM1, and PTGS2 in cumulus cell level. Otherwise, the current non-invasive method can be used in exploring various causes of infertility that may affect these gene expressions at the cumulus cell level. Nevertheless, this method can also be used in assessing the ODC in various cohorts of women or as an improvement of markers following targeted tools or procedures by evaluating the advancement of these gene expressions following the targeted intervention.

Correction: Patients with gestational diabetes mellitus may be treated in both early and late pregnancy, especially in patients with pre-pregnancy overweight: A cross-sectional study in Japan.

[This corrects the article DOI: 10.1007/s13340-023-00646-w.].

Survey of Transitional Care Between Pediatrics and Obstetrics/Gynecology in Japan.

Purpose: This study's aim was to determine the actual status of transitional care for patients with pediatric cancer (PPCs) in Japan by surveying obstetricians/gynecologists. Methods: A questionnaire survey on transitional medicine was conducted in the form of an online questionnaire at 579 major training facilities nationwide, which were registered with the Japanese Society of Obstetrics and Gynecology. Results: While 40% of the facilities had received referrals for PPCs, only 13% provided transitional care specifically for PPCs. The most common problems with referrals were related to "insufficient explanation." In addition, at facilities with no experience treating PPCs, many respondents commented that they did not know how to follow the progression of the disease. Regarding the necessity of obstetrics/gynecology visits for PPCs, more than half of the respondents at facilities with experience treating PPCs answered that such visits were "necessary"; only 1% answered that they were "unnecessary." On the other hand, 37% of the facilities that had no experience treating PPCs answered that it was "necessary," whereas 4% answered that it was "unnecessary." Conclusions: This survey of the actual status of transitional care between pediatrics and obstetrics/gynecology in Japan identified issues to be addressed for the spread of transitional care. The results suggest that, in the future, health care professionals need education to increase their knowledge, and that patient education that leads to patients' awareness of their own self-management is necessary.

Survey on the implementation status and reproductive outcomes of oocyte and ovarian tissue cryopreservation in Japan: Historical comparison with nationwide surveys.

PURPOSE: To clarify the reproductive outcomes of fertility preservation (FP) treatment. METHODS: We conducted a mailed-in questionnaire survey at institutions certified by the Japan Society of Obstetrics and Gynecology to investigate the number of oocyte cryopreservations (OC) and ovarian tissue cryopreservations (OTC) performed from December 2016 to the end of 2020. And, we conducted a detailed investigation of cases in which frozen specimens were used during the investigation period, and made historical comparisons with previous nationwide studies. RESULTS: Responses were received from 114 out of 150 facilities (response rate: 76.0%) for OC and 43 out of 51 for OTC (response rate: 84.3%). Breast cancer was the most common disease among patients whose FP specimens were used. During the study period, 1237 OCs and 198 OTCs were performed. In addition, 57 cycles of embryo transfer (ET) using cryopreserved oocytes and 12 cases of ovarian tissue transplantation (OTT) were performed. The mean age of patients who underwent ET using cryopreserved oocytes was 34.8 (±5.8) years, with a median age of 36 years. The pregnancy rate per ET using cryopreserved oocytes was 26.3% and the live birth rate (LBR) was 17.5%. Further, the LBR per patient was 43.3%, and the pregnancy rate following OTTs was 33.3%. Also, controlled ovarian stimulation using the random start method or the combination of aromatase inhibitors had no effect on pregnancy outcome. CONCLUSION: Implementation of both OCs and OTCs have markedly increased over time in Japan, with comparable reproductive outcomes as other reports.

Differences Between Cancer Survivors and Healthy Subjects in Factors that Facilitate and Obstruct the Use of the Foster Parent System and Special Adoption System: A Nationwide Cross-Sectional Study in Japan.

Purpose: To investigate factors that obstruct and facilitate the use of the foster parent and special adoption systems (i.e., foster systems) by cancer survivors, and examine how to effectively provide information. Methods: This was a cross-sectional study that compared the results of a questionnaire survey of foster parents and adoptive parents (i.e., foster parents) who were and were not cancer survivors belonging to foster parent associations in 33 locations in Japan. This study was supported by a 2022 Ministry of Health, Labor, and Welfare Grant-in-Aid for Scientific Research (Grant No. 20EA1004). Results: "Lack of information," an obstructive factor and "Sympathetic understanding and cooperation from my partner and family," a facilitative factor were the highest score in both groups. Significant differences between the two groups were found in "Support from government agencies and others for foster parents," a facilitative factor, which was lower in the cancer survivors' group. There were no other significant differences between both the groups. Conclusion: This study found that when considering the use of the foster systems, a lack of information was the biggest obstructive factor and family understanding was the most helpful for both cancer survivors and noncancer groups. It was thought that stronger government support for cancer survivors might encourage cancer survivors to consider becoming foster parents. It would be effective for cancer treatment facilities, reproductive medical facilities, the government, and foster parent associations to work together to provide information carefully to cancer survivors.

Prospective analysis of patient-reported outcomes and physician-reported outcomes with gynecologic cancer chemotherapy.

OBJECTIVE: Gynecologic cancer chemotherapy impacts the quality of life (QOL) of patients, with lasting adverse events that may require treatment adjustments or discontinuation. Consequently, real-time symptom monitoring before outpatient visits has resulted in improved QOL for patients and extended survival times. This study investigated whether there are differences between electronic patient-reported outcomes (e-PRO-CTCAE) and physician-assessed outcomes (NCI-CTCAE) evaluated in an outpatient setting in gynecologic cancer chemotherapy. METHODS: The study was conducted on 50 patients who received their first chemotherapy treatment at St. Marianna University Hospital Obstetrics and Gynecology from July 1, 2021 to December 31, 2022. PRO-CTCAE and NCI-CTCAE were evaluated at each instance of chemotherapy and 2 weeks after. The PRO-CTCAE was additionally collected weekly using e-PRO. RESULTS: The values for "Joint Pain," "Nausea," "Taste Disturbance," "Constipation," "Insomnia," "Fatigue," "Limb Edema," and "Concentration Impairment" were consistently higher in PRO-CTCAE than in NCI-CTCAE, indicating that physicians underestimated the severity of adverse events. In contrast, there was no significant difference in "Peripheral Neuropathy," demonstrating that physicians had a good understanding of this condition in patients. The weekly responses obtained from e-PRO revealed that symptom exacerbations peaked outside of clinic visits. CONCLUSIONS: This study demonstrated physicians tend to underestimate most adverse events. Moreover, the responses using e-PRO revealed peak symptom deterioration occurred outside of outpatient visits. This suggested that e-PRO and actions taken in response to them can improve patients' QOL.

Significance and Influence of Suturing for Ovarian Tissue Transplantation.

The purpose of this animal study was to verify the effect of suturing on graft function in ovarian tissue transplantation. Ovaries from 2-week-old rats were transplanted orthotopically into the ovaries of 8-week-old female Wistar rats. The various transplantation methods used were insertion into the ovarian bursa without suturing (group A: control), suturing with a single 6-0 Vicryl stitch (group B: 6-0*1), suturing with a single 10-0 Vicryl stitch (group C: 10-0*1), and suturing with three 10-0 Vicryl stitches (group D: 10-0*3). Two weeks after transplantation, the transplanted ovaries were evaluated histologically and for gene expression. Engraftment rates of the donor ovaries 14 days after transplantation were 62.5%, 100%, 91.7%, and 100% in groups A, B, C, and D, respectively, significantly lower in group A than in the other groups. In terms of gene expression, TNFα levels were significantly higher in group D, and GDF9 and follicle-stimulating hormone receptor (FSHR) levels were significantly lower in group D than in groups A and B. The number of primordial follicles evaluated by HE staining was significantly lower in groups B, C, and D than in group A. Compared to orthotopic transplantation without sutures, direct suturing to the host improved the engraftment rate, although increasing the number of sutures increased inflammatory marker levels and decreased the number of primordial follicles. We believe that it is important to perform ovarian tissue transplantation using optimal suture diameter for good adhesion, but with a minimum number of sutures to preserve ovarian function.

Optimal cervical-ripening method for labor induction in Japan after the era of controlled-release dinoprostone vaginal insert.

OBJECTIVE: To investigate the predictive value of obstetric findings when using dinoprostone (prostaglandin E2 [PGE2]) vaginal inserts for cervical ripening, and to assess the optimal cervical-ripening method between PGE2 vaginal insert and/or cervical dilators. METHODS: This prospective observational study enrolled pregnant women who underwent cervical ripening for labor induction in 37-41 week' gestation in 2020. In evaluation 1, optimal obstetric findings predictive of rapid cervical ripening using PGE2 were assessed. In evaluation 2, the duration from PGE2 administration to labor onset and perinatal outcomes were compared between cases in which only PGE2 was used and cases that were treated with PGE2 after mechanical cervical dilators (Dilapan®) for extremely immature cervical ripening (uterine cervical os <2 cm). RESULTS: In evaluation 1, uterine dilatation before the use of a PGE2 vaginal insert was mostly correlated with the time from PGE2 administration to labor onset (r = -0.428, p < 0.001). When the uterine cervical os dilatation was ≥2 cm, a shorter time-to-labor onset was found. In addition, os dilatation, effacement, and station at the time of PGE2 vaginal insert removal also significantly progressed. In evaluation 2, the median duration from PGE2 administration to labor onset was 1740 min in cases where only PGE2 was used, and 610 min in those where PGE2 was used after mechanical cervical dilators (p = 0.011). CONCLUSION: PGE2 vaginal inserts are relatively effective when the uterine cervical os is ≥2 cm in diameter. However, in cases of extremely immature cervical-ripening, it was feasible to use PGE2 vaginal inserts before mechanical cervical dilatation.

Patients with gestational diabetes mellitus may be treated in both early and late pregnancy, especially in patients with pre-pregnancy overweight: A cross-sectional study in Japan.

The significance of diagnosing gestational diabetes mellitus (GDM) in early pregnancy is controversial. We used the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria to investigate whether clinical background and neonatal outcomes differ depending on when GDM is diagnosed in early or late pregnancy. This was a single-center, observational study conducted between November 2012 and March 2020 at St. Marianna University Hospital (Kawasaki, Japan). We compared the background and perinatal outcomes of patients with GDM depending on the time of diagnosis (at < 24 gestational weeks or ≥ 24 weeks). Insulin sensitivity index, homeostasis model assessment of insulin resistance, and ß-cell function were calculated from a 75-g oral glucose tolerance test. Stratified analysis was performed by pre-pregnancy BMI in patients with early GDM. As a result, in the 507 patients, 89.9% gave birth at our hospital. The pre-pregnancy BMI was significantly higher in patients with early GDM than in those with late GDM (the median [interquartile range], 22.7 [20.3, 26.3] and 21.5 [19.3, 23.8] kg/m2, respectively; p = 0.001). Perinatal outcomes were not different between the two groups. However, in the subgroup analysis of patients with early GDM, the prevalence of large-for-gestational-age infants was significantly higher in the group with overweight (15.4% vs 2.1%, respectively; p = 0.008). In conclusion, patients with GDM using the IADPSG criteria in early pregnancy may be treated, especially in patients with pre-pregnancy overweight.

The study of the efficiency of in vitro maturation of ovarian tissue oocytes in pediatric patients.

PURPOSE: Although recent in vitro maturation (IVM) studies in pediatric patients have demonstrated successful retrieval and maturation of oocytes, the studies included only a small number of premenarchal patients. In the present study, we examined the potential use of oocyte retrieval and maturation for pediatric patients who undergo ovarian tissue cryopreservation (OTC). METHODS: We retrospectively examined the clinical records of pediatric patients who underwent OTC at our institution between October 2015 and December 2022. Data on the age, primary disease, menstrual history, pre-procedure chemotherapy, anti-Müllerian hormone (AMH) level, number of oocytes collected ex vivo from ovarian tissue, and number of mature oocytes from IVM were examined. RESULTS: Data of 60 pediatric patients (aged 1 to 17 years) were included for analysis. Oocytes were retrieved from 36 patients; the oocytes of 18 of these patients could be cryopreserved. The IVM rate was significantly lower in the premenarchal patients than in the postmenarchal patients. The number of mature oocytes retrieved from IVM was higher in the no-chemotherapy group than in the chemotherapy group. A significant positive correlation was observed between the AMH level and the IVM outcomes. CONCLUSION: Oocyte retrieval and maturation in pediatric patients undergoing OTC is particularly useful in those not receiving chemotherapy. In patients receiving chemotherapy, the AMH level may be useful for predicting the IVM outcome. Activation of the oocyte maturation process in vivo in pediatric patients and better understanding of the major regulators of oocyte maturation are necessary to improve the utility of the IVM procedure.

Ultrasound Doppler Findings in Fetal Vascular Malperfusion Due to Umbilical Cord Abnormalities: A Pilot Case Predictive for Cerebral Palsy.

Fetal Vascular Malperfusion (FVM), a pathologic condition in the feto-placental circulation, is a chronic vaso-occlusive disorder in the umbilical venous blood flow. Microthrombi are caused by the umbilical cord's blood flow deficiency in a congested umbilical vein, which also causes microvascular damage to fetal organs, especially the brain, resulting in cerebral palsy. Thrombo-occlusive events also adversely affect the upstream chorionic or stem vessels in the placenta, resulting in fetal growth restriction and fetal hypoxia. An umbilical cord structural anomaly or multiple entanglements may involve FVM. In the present report, we demonstrate a case of FVM caused by multiple umbilical cord abnormalities obtained from antenatal ultrasound Doppler findings, and we also discuss FVM, which is chronically associated with CP, comparing the ultrasonographic findings to the pathologic findings.

Challenges to Widespread Use of Fertility Preservation Facilities for Pediatric Cancer Patients in Japan.

Purpose: Although fertility preservation for pediatric cancer patients is becoming more widespread in Japan, some facilities do not provide sufficient information regarding fertility. This study aimed to elucidate the problems pertaining to the lack of information about fertility among patients. Methods: Based on a 2020 survey, seminars addressing fertility preservation were held from the Designated Pediatric Cancer Care Hospitals in each of the seven blocks in Japan to their partner hospital (pediatric cancer hospitals). The seminar consisted of lectures and group discussions, and a questionnaire was also administered after each seminar. Results: In the group discussions, a lack of explanations to patients and explanatory materials for children were cited as issues by many facilities. The survey results revealed a lack of material explaining fertility preservation and a lack of knowledge among health care providers. There were also many requests to use the patient explanation videos presented at the seminar. Conclusion: The results indicate that further education for health care providers by seminar and other sources and enhancement of explanatory materials are important for fertility preservation in pediatric cancer hospitals in Japan.

Investigation of an efficient method of oocyte retrieval by dual stimulation for patients with cancer.

Purpose: To examine the optimal timing of second ovarian stimulation using the dual stimulation method for good ovarian responders with cancer undergoing oocyte retrieval for fertility preservation. Methods: A retrospective analysis was conducted using data from 69 patients with cancer who underwent oocyte retrieval for fertility preservation at four Japanese institutions during 2010-2021. Twenty-two patients underwent two oocyte retrievals for fertility preservation. We studied the relationship between the initial number of oocytes retrieved via dual stimulation and risk of ovarian enlargement as well as the appropriate waiting interval between the end of the first ovarian stimulation and beginning of the second ovarian stimulation. Results: The risk of ovarian enlargement was high when the initial number of oocytes retrieved via dual stimulation was ≥5. An 8-day waiting interval may be more effective for performing a second ovarian stimulation oocyte retrieval in these cases, although the difference was not significant. Conclusions: This study provides one policy for effectively managing ovarian enlargement and timing of second ovarian stimulation during oocyte retrieval via the dual stimulation method for patients with cancer undergoing fertility preservation. If more facilities implement this procedure, more oocytes may be obtained in a short period for fertility preservation purposes.

Individualized management of vasa previa and neonatal outcomes.

OBJECTIVE: To describe our individualized management protocol for women with an antenatal diagnosis of vasa previa (VP) and to report maternal and neonatal outcomes in patients managed according to our protocol. METHODS: A retrospective study of prospectively collected data of antenatally diagnosed VP managed at our hospital between 2014 and 2021. Obstetric and neonatal outcomes were reviewed and analyzed. RESULTS: Fourteen cases of antenatally diagnosed VP in 5150 total deliveries were analyzed (0.3%) Five cases (36%) of VP were diagnosed during the routine fetal morphological ultrasound screening, and nine cases (64%) were referred to our hospital due to perinatal complications. There were nine cases that required hospitalization (due to fetal growth restriction [FGR] [1], preterm labor [3], patients' request [5]). The other five were asymptomatic. Eight patients were delivered by scheduled cesarean section at around 36 weeks and only three neonates were admitted to NICU with transient tachypnea of newborn. However, six patients required CS before the scheduled dates because of other complications (preterm labor [3], abnormal cardiotocogram patterns [1], FGR [1] and twin pregnancy [1]). Four neonates born by CS before their scheduled dates were admitted to NICU. No cases required prolonged hospitalization and there were no serious neonatal complications. CONCLUSION: Individualized management may lead to favorable outcomes with VP. Outpatient management may be considered in patients without risk factors. However, maternal hospitalization and earlier scheduled CS should be considered in symptomatic patients or those at risk for preterm delivery.

The spectrum of in vitro maturation in clinical practice: the current insight.

In vitro oocyte maturation (IVM) has been used worldwide. Despite the long-term implementation, the uptake of this procedure to complement current in vitro fertilization (IVF) remains low. The main reason is likely due to the non-synchronization of protocol and definition criteria, leading to difficulty in collective proper outcome data worldwide and, thus, lack of understanding of the exact IVM procedure. The review aims to consolidate the current clinical practice of IVM by dissecting relevant publications to be tailored for a current spectrum of clinical practice. Nevertheless, the background theories of oocyte maturation were also explored to provide a comprehensive understanding of the basis of IVM theories. Additional discussion of other potential uses of IVM in the future, such as in ovarian tissue cryopreservation known as OTO-IVM for fertility preservation and among women with diminished ovarian reserve, was also explored. Otherwise, future collaboration among all IVM centers is paramount for better collection of clinical data to provide valid recommendations for IVM in clinical practice, especially in molecular integrity and possible DNA alteration if present for IVM offspring outcome safety purposes.

Oral-malodor measurement and intention to quit smoking in men: A before-after study.

INTRODUCTION: Few studies have examined the effect of feedback based on oral-malodor measurements on the motivation to quit smoking. Therefore, this study examined whether oral-malodor measurements were associated with the intention to quit smoking. METHODS: This retrospective, uncontrolled before-after study invited smokers to a workplace health event in 2019 and 2020 to motivate them to quit smoking. They attended seminars on oral health and smoking cessation aids, and then underwent respiratory function and oral-malodor measurements using exhaled and oral cavity air, respectively. Intention to quit smoking was evaluated by answers to questions regarding the intention to quit in the next 1 or 6 months in questionnaires collected before and after the event. This study analyzed 241 men aged 20-54 years (mean: 33.2 ± 10.5) to examine factors associated with the intention to quit in multivariable logistic regression analyses for age, tobacco type (cigarettes and heated-tobacco products), and category of tobacco consumption. RESULTS: Before the event, 8.7%, 17.0%, and 74.3% of smokers had intended to quit in the next month, the next six months, or had no intention to quit, respectively. After the event, the respective percentages were 17.8%, 26.6%, and 55.6%. A higher methyl mercaptan concentration, a volatile sulfide component of oral malodor, was significantly associated with the intention to quit in the next month (adjusted odds ratio, AOR=4.24; 95% CI: 1.52-11.8, p=0.006). The participants with higher daily tobacco consumption were less likely to acquire the intention to quit in the next six months (AOR=0.37; 95% CI: 0.15-0.92, p=0.032). Other variables, such as lung age deficit, exhaled CO concentration, and hydrogen sulfide concentration (another component of oral malodor), were not significantly associated. CONCLUSIONS: Oral-malodor measurement feedback may help motivate men to quit smoking in the next 1 month rather than in the next six months.

Effect of a web-based fertility preservation training program for medical professionals in Japan.

BACKGROUND: Our web-based training program called "Educating Medical Professionals about Reproductive Issues in Cancer Healthcare" aims to help healthcare professionals communicate promptly with patients and survivors who are adolescents and young adults, with information pertinent to reproductive health issues such as the risk of infertility and fertility preservation. METHODS: The study participants were professional healthcare providers, including physicians, nurses, pharmacists, social workers, midwives, psychologists, laboratory technicians, genetic counselors, and dieticians. Pre- and post- and 3-month follow-up tests consisting of 41 questions were administered to measure changes in knowledge and confidence. The participants also received a follow-up survey that covered confidence, communication techniques, and practice habits. A total of 820 healthcare providers participated in this program. RESULTS: The mean total score from the pre-test to the post-test grew significantly (p < 0.01), and participants' self-confidence increased. In addition, there was a change in the behavior of healthcare providers, who began asking about patients' marital status and parity. CONCLUSION: Our web-based fertility preservation training program improved knowledge and self-confidence regarding fertility preservation issues among healthcare providers caring for adolescents and young adult cancer patients and survivors.

Investigation of Fertility Preservation Education Videos for Pediatric Patients Based on International and Historical Survey.

Purpose: Recently, direct communication with children about cancer seems to have shifted, but little is known about communication regarding discussions of future infertility risk due to cancer therapy. This study conducted cross-cultural comparisons between Japan and the United States to clarify communication patterns about cancer notification and develop appropriate information about fertility issues. Methods: An online survey was distributed to members of the Japanese Society of Pediatric Hematology/Oncology in July 2019 and the American Society of Pediatric Hematology/Oncology in July 2020. Based on the results from the survey, we developed three types of educational videos: a prepubertal version A, B, and a pubertal version. Next, we conducted a survey to assess whether these were appropriate for clinical practice. Results: We analyzed 325 physicians in Japan and 46 in the United States. In Japan, 80.5%, 91.7%, and 92.1% of the physicians notified patients aged 7-9, 10-14, and 15-17 years of their cancer diagnosis directly, respectively, compared within the United States, where the rate was 100%, regardless of age. Further, 9% and 45% of physicians in Japan and the United States, respectively, discuss fertility issues directly with patients aged 7-9 years. In the survey to assess the educational videos, 85% of the physicians preferred to use the educational videos in clinical practice. Conclusion: This is the first step in bringing concordance to communication patters for emerging cancer care around the globe and that this study and its intervention arm provide guidance in ways that ensure global equity in care.

Drug-Facilitated Crystallization of Spray-Dried CD-MOFs with Tunable Morphology, Porosity, And Dissolution Profile.

Metal-organic frameworks (MOFs) with versatile functionalities have applications in environmental science, sensor separation, catalysis, and drug delivery. In particular, MOFs used in drug delivery should be biodegradable and easy to control. In this study, spray-dried cyclodextrin-based MOFs (CD-MOFs) with tunable crystallinity, porosity, and dissolution properties were fabricated. The spray-drying precursor properties, such as ethanol volume ratio, incubation time, and precursor concentration, were optimized for controlled crystallization. On the basis of the morphology, X-ray diffraction peak intensity, and specific surface areas of the spray-dried CD-MOF products, they were categorized as amorphous, partially crystalline, and highly crystalline. An active pharmaceutical ingredient ketoconazole (KCZ) was introduced into the precursor to prepare KCZ-containing CD-MOFs. The surface areas of these products were greater by 3-fold (292 m2/g) than that of the plain CD-MOF (94.1 m2/g) prepared using the same parameters. The presence of KCZ in the hydrophobic cavity between the two γ-CD molecules was correlated to the CD-MOF crystal growth. Additionally, CD-MOF particles exhibited different dissolution behaviors on the basis of the position of KCZ in the MOF. These spray-dried CD-MOFs with tunable morphology, specific surface area, and dissolution could have potential applications in various fields.