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World Health Organization (WHO) predicts that cancer incidence will increase in the future, thus research involving anticancer agents such as nanoparticles has gained significant importance. Nanoparticles can be made from various materials, but the focus on polymeric chitosan and/or carrageenan-based nanoparticles is significant. Research on these materials investigates dynamic parameters of in vitro drug release, stability under working conditions and stability under storage conditions (in vitro kinetics characterisations). Here, a literature review is conducted to provide in-depth insights on research methodology trends, drawbacks, suitability, suggestions for improvements and findings related to polymeric carrageenan and/or chitosan nanoparticles for anticancer therapy. Journal articles involving nanoparticles made from chitosan and/or carrageenan containing anticancer agents published between 2017 and 2022 were acquired through Google Scholar search using relevant keywords. Generally, the methods used to investigate drug release kinetics of nanoparticles can be categorised into dialysis membrane, sample and separate or direct measurement methods. Studies on the response of physiochemical characteristics towards changes in environment do not vary highly and are generalisable. Stability studies primarily measure the physicochemical changes of nanoparticles as a response measurement towards storage conditions. Both drug release selectivity and physicochemical characteristics response in different pH environments were found to be predictable via the ionisation of polymers and drugs used in different pH. The size of the nanoparticles formed during polyelectrolyte complexation process was found to be at its minimum at a balanced pH, possibly due to increased polymer-polymer attraction. The methods used for in vitro kinetics studies were generalised, and suggestions to address potential sources of errors were given in the current review. The selectivity of drug release and changes in physicochemical characteristics of the nanoparticles in different pH environments were found to largely coincide with the principles of ionisation of nanoparticle constituent.

Commercially available topical oral drugs in current markets have low efficacy in delivery active load to the infected site due to poor formulation. Delivery of the active ingredients proven to be challenging as compared to skin due the presence of saliva and low shear. The aim of this project to improve formulation and characterised suitable hydrogels which later will be incorporated with nanoparticle drug for oral cancer. The gels are formulated at different pH values (4, 7, 10) and concentrations as such (0.1%, 0.15%, 0.2%, 0.25%, 0.5% and 1.0% for alginate whereas kappa-carrageenan and iota-carrageenan were formulated with 0.25%, 0.5% and 1.0%). The viscosity and zeta potential of the formulated gels are studied using HAAKE™ MARS™ rheometer and Zetasiser Nano-Z respectively. Findings revealed both 1% of kappa-carrageenan and 1% iota-carrageenan of pH 4 and pH 7 are the best candidates for nanoparticle drug delivery as the viscosity and zeta potential for 1% kappa-carrageenan (pH 4), 1% kappa-carrageenan (pH 7), 1% iota-carrageenan (pH 4), and 1% iota-carrageenan (pH 7) amongst the highest as such 70.507±6.190, 61.040±3.199, 59.490±7.799, 67.953±2.034 Pa·s, correspondingly with zeta potential value of -19.4 mV, -20.6 mV, -33.1 mV and -30.4 mV. All hydrogels formulated with different concentration were affected by pH values, by having pH value 4 and 7 appeared to have high viscosity with pseudoplastic behaviour based on the rheological profile, except for alginate due to high density sodium alginate was used in this study.

The data presented here is the liquid chromatography and mass spectrometry (LC-MS) profile of phytochemical compounds in the aqueous extract of Syzygium polyanthum (Wight) Walp. leaves. This plant is consumed raw and sometimes added to local dishes of people in Southeast Asia countries. Most importantly, it has ethnomedicinal values mainly in treating diabetes and hypertension, and at the same time, this plant has anti-microbial, anti-oxidant, anti-cancer, and anti-tumor properties [1]. There are chemical composition variations reported between the same species of different geographical locations, which eventually affect the plant's therapeutic potential [2,3]. This dataset represents the identified compounds for S. polyanthum (Wight) Walp. leaves, a variant collected from Kuantan, a city located in the Pahang state on the East Coast of Peninsular Malaysia. The leaves were then dried in an open-air at room temperature for three weeks, ground, and then macerated in water inside a bath-sonicator, freeze-dried, and then run using LCMS. The LCMS was run using the ultra-performance liquid chromatography equipped with an electrospray time-of-flight mass spectrometer detector, operated in a negative-ion mode. The mass spectral features from samples raw data were matched with Traditional Medicine (en) and Waters Screening libraries in the Waters UNIFI™ Scientific Information System software version 1.7 (Waters, USA) for compounds identification.

Objectives: To test whether intraoperative ultrasound can reduce the incidence of early and late complications following surgical removal of products of conception., Design: This was a prospective, multicentre, randomised, open clinical trial to assess feasibility. It was performed in two University Teaching hospitals in the West Midlands, England. The population consisted of women aged 16 years or over who were referred for surgical management of miscarriage. Patients were randomised to surgical management of miscarriage with either continuous intraoperative ultrasound or without intraoperative ultrasound. Process outcomes included the proportion of eligible women screened and proportion of eligible women randomised, attrition rates, evaluation of outcome measurement tools and acceptability. The primary clinical outcome was a composite outcome of unsuccessful procedure or a complication., Results: Fifty-nine women requiring surgical management of miscarriage were randomised. The conversion rate for entry into the trial was 59/79(75 %; 95 %CI = 64-84 %). The composite clinical outcome was attained in 5/27(19 %) patients who had surgery without ultrasound and 7/28(25 %) patients who had surgery with ultrasound (RR = 0.74;95 %CI = 0.26, 2.10). When we excluded the patients that could not attend their hysteroscopy appointment, due to COVID-19 pandemic, 5/27(19 %) of patients who had surgery without ultrasound and 5/25(20 %) of patients who had surgery with ultrasound attained the composite clinical outcome (RR = 0.93;95 %CI = 0.30, 2.90)., Conclusions: This multicentre pilot study showed that a large RCT comparing surgical management of miscarriage with and without intraoperative ultrasound is feasible., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Virus-like particles (VLPs) are known as self-assembled, non-replicative and non-infectious protein particles, which imitate the formation and structure of original wild type viruses, however, lack the viral genome and/or their fragments. The capacity of VLPs to encompass small molecules like nucleic acids and others has made them as novel vessels of nanocarriers for drug delivery applications. In addition, VLPs surface have the capacity to achieve variation of the surface display via several modification strategies including genetic modification, chemical modification, and non-covalent modification. Among the VLPs nanocarriers, Hepatitis B virus core (HBc) particles have been the most encouraging candidate. HBc particles are hollow nanoparticles in the range of 30-34 nm in diameter and 7 nm thick envelopes, consisting of 180 or 240 copies of identical polypeptide monomer. They also employ a distinctive position among the VLPs carriers due to the high-level synthesis, which serves as a strong protective capsid shell and efficient self-assembly properties. This review highlights on the bioengineering of HBc particles as dynamic nanocarriers for in vivo delivery and specific targeting to solid tumours., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Trial Design: A randomised, parallel-group, double-blind, placebo-controlled multicentre study with health economic and nested qualitative studies to determine if mifepristone (Mifegyne ® , Exelgyn, Paris, France) plus misoprostol is superior to misoprostol alone for the resolution of missed miscarriage., Methods: Women diagnosed with missed miscarriage in the first 14 weeks of pregnancy were randomly assigned (1 : 1 ratio) to receive 200 mg of oral mifepristone or matched placebo, followed by 800 μg of misoprostol 2 days later. A web-based randomisation system allocated the women to the two groups, with minimisation for age, body mass index, parity, gestational age, amount of bleeding and randomising centre. The primary outcome was failure to pass the gestational sac within 7 days after randomisation. The prespecified key secondary outcome was requirement for surgery to resolve the miscarriage. A within-trial cost-effectiveness study and a nested qualitative study were also conducted. Women who completed the trial protocol were purposively approached to take part in an interview to explore their satisfaction with and the acceptability of medical management of missed miscarriage., Results: A total of 711 women, from 28 hospitals in the UK, were randomised to receive either mifepristone plus misoprostol (357 women) or placebo plus misoprostol (354 women). The follow-up rate for the primary outcome was 98% (696 out of 711 women). The risk of failure to pass the gestational sac within 7 days was 17% (59 out of 348 women) in the mifepristone plus misoprostol group, compared with 24% (82 out of 348 women) in the placebo plus misoprostol group (risk ratio 0.73, 95% confidence interval 0.54 to 0.98; p  = 0.04). Surgical intervention to resolve the miscarriage was needed in 17% (62 out of 355 women) in the mifepristone plus misoprostol group, compared with 25% (87 out of 353 women) in the placebo plus misoprostol group (risk ratio 0.70, 95% confidence interval 0.52 to 0.94; p  = 0.02). There was no evidence of a difference in the incidence of adverse events between the two groups. A total of 42 women, 19 in the mifepristone plus misoprostol group and 23 in the placebo plus misoprostol group, took part in an interview. Women appeared to have a preference for active management of their miscarriage. Overall, when women experienced care that supported their psychological well-being throughout the care pathway, and information was delivered in a skilled and sensitive manner such that women felt informed and in control, they were more likely to express satisfaction with medical management. The use of mifepristone and misoprostol showed an absolute effect difference of 6.6% (95% confidence interval 0.7% to 12.5%). The average cost per woman was lower in the mifepristone plus misoprostol group, with a cost saving of £182 (95% confidence interval £26 to £338). Therefore, the use of mifepristone and misoprostol for the medical management of a missed miscarriage dominated the use of misoprostol alone., Limitations: The results from this trial are not generalisable to women diagnosed with incomplete miscarriage and the study does not allow for a comparison with expectant or surgical management of miscarriage., Future Work: Future work should use existing data to assess and rank the relative clinical effectiveness and safety profiles for all methods of management of miscarriage., Conclusions: Our trial showed that pre-treatment with mifepristone followed by misoprostol resulted in a higher rate of resolution of missed miscarriage than misoprostol treatment alone. Women were largely satisfied with medical management of missed miscarriage and would choose it again. The mifepristone and misoprostol intervention was shown to be cost-effective in comparison to misoprostol alone., Trial Registration: Current Controlled Trials ISRCTN17405024., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 25, No. 68. See the NIHR Journals Library website for further project information.

Objective: To assess the cost-effectiveness of mifepristone and misoprostol (MifeMiso) compared with misoprostol only for the medical management of a missed miscarriage., Design: Within-trial economic evaluation and model-based analysis to set the findings in the context of the wider economic evidence for a range of comparators. Incremental costs and outcomes were calculated using nonparametric bootstrapping and reported using cost-effectiveness acceptability curves. Analyses were performed from the perspective of the UK's National Health Service (NHS)., Setting: Twenty-eight UK NHS early pregnancy units., Sample: A cohort of 711 women aged 16-39 years with ultrasound evidence of a missed miscarriage., Methods: Treatment with mifepristone and misoprostol or with matched placebo and misoprostol tablets., Main Outcome Measures: Cost per additional successfully managed miscarriage and quality-adjusted life years (QALYs)., Results: For the within-trial analysis, MifeMiso intervention resulted in an absolute effect difference of 6.6% (95% CI 0.7-12.5%) per successfully managed miscarriage and a QALYs difference of 0.04% (95% CI -0.01 to 0.1%). The average cost per successfully managed miscarriage was lower in the MifeMiso arm than in the placebo and misoprostol arm, with a cost saving of £182 (95% CI £26-£338). Hence, the MifeMiso intervention dominated the use of misoprostol alone. The model-based analysis showed that the MifeMiso intervention is preferable, compared with expectant management, and this is the current medical management strategy. However, the model-based evidence suggests that the intervention is a less effective but less costly strategy than surgical management., Conclusions: The within-trial analysis found that based on cost-effectiveness grounds, the MifeMiso intervention is likely to be recommended by decision makers for the medical management of women presenting with a missed miscarriage., Tweetable Abstract: The combination of mifepristone and misoprostol is more effective and less costly than misoprostol alone for the management of missed miscarriages., (© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of mifepristone and misoprostol is more effective than administering misoprostol alone. We investigated whether treatment with mifepristone plus misoprostol would result in a higher rate of completion of missed miscarriage compared with misoprostol alone., Methods: MifeMiso was a multicentre, double-blind, placebo-controlled, randomised trial in 28 UK hospitals. Women were eligible for enrolment if they were aged 16 years and older, diagnosed with a missed miscarriage by pelvic ultrasound scan in the first 14 weeks of pregnancy, chose to have medical management of miscarriage, and were willing and able to give informed consent. Participants were randomly assigned (1:1) to a single dose of oral mifepristone 200 mg or an oral placebo tablet, both followed by a single dose of vaginal, oral, or sublingual misoprostol 800 μg 2 days later. Randomisation was managed via a secure web-based randomisation program, with minimisation to balance study group assignments according to maternal age (<30 years vs ≥30 years), body-mass index (<35 kg/m 2 vs ≥35 kg/m 2 ), previous parity (nulliparous women vs parous women), gestational age (<70 days vs ≥70 days), amount of bleeding (Pictorial Blood Assessment Chart score; ≤2 vs ≥3), and randomising centre. Participants, clinicians, pharmacists, trial nurses, and midwives were masked to study group assignment throughout the trial. The primary outcome was failure to spontaneously pass the gestational sac within 7 days after random assignment. Primary analyses were done according to intention-to-treat principles. The trial is registered with the ISRCTN registry, ISRCTN17405024., Findings: Between Oct 3, 2017, and July 22, 2019, 2595 women were identified as being eligible for the MifeMiso trial. 711 women were randomly assigned to receive either mifepristone and misoprostol (357 women) or placebo and misoprostol (354 women). 696 (98%) of 711 women had available data for the primary outcome. 59 (17%) of 348 women in the mifepristone plus misoprostol group did not pass the gestational sac spontaneously within 7 days versus 82 (24%) of 348 women in the placebo plus misoprostol group (risk ratio [RR] 0·73, 95% CI 0·54-0·99; p=0·043). 62 (17%) of 355 women in the mifepristone plus misoprostol group required surgical intervention to complete the miscarriage versus 87 (25%) of 353 women in the placebo plus misoprostol group (0·71, 0·53-0·95; p=0·021). We found no difference in incidence of adverse events between the study groups., Interpretation: Treatment with mifepristone plus misoprostol was more effective than misoprostol alone in the management of missed miscarriage. Women with missed miscarriage should be offered mifepristone pretreatment before misoprostol to increase the chance of successful miscarriage management, while reducing the need for miscarriage surgery., Funding: UK National Institute for Health Research Health Technology Assessment Programme., (This is an Open Access article under the CC BY-NC-ND 4.0 license.)

Background: Progesterone is essential for a healthy pregnancy. Several small trials have suggested that progesterone therapy may rescue a pregnancy in women with early pregnancy bleeding, which is a symptom that is strongly associated with miscarriage., Objectives: (1) To assess the effects of vaginal micronised progesterone in women with vaginal bleeding in the first 12 weeks of pregnancy. (2) To evaluate the cost-effectiveness of progesterone in women with early pregnancy bleeding., Design: A multicentre, double-blind, placebo-controlled, randomised trial of progesterone in women with early pregnancy vaginal bleeding., Setting: A total of 48 hospitals in the UK., Participants: Women aged 16-39 years with early pregnancy bleeding., Interventions: Women aged 16-39 years were randomly assigned to receive twice-daily vaginal suppositories containing either 400 mg of progesterone or a matched placebo from presentation to 16 weeks of gestation., Main Outcome Measures: The primary outcome was live birth at ≥ 34 weeks. In addition, a within-trial cost-effectiveness analysis was conducted from an NHS and NHS/Personal Social Services perspective., Results: A total of 4153 women from 48 hospitals in the UK received either progesterone ( n  = 2079) or placebo ( n  = 2074). The follow-up rate for the primary outcome was 97.2% (4038 out of 4153 participants). The live birth rate was 75% (1513 out of 2025 participants) in the progesterone group and 72% (1459 out of 2013 participants) in the placebo group (relative rate 1.03, 95% confidence interval 1.00 to 1.07; p  = 0.08). A significant subgroup effect (interaction test p  = 0.007) was identified for prespecified subgroups by the number of previous miscarriages: none (74% in the progesterone group vs. 75% in the placebo group; relative rate 0.99, 95% confidence interval 0.95 to 1.04; p  = 0.72); one or two (76% in the progesterone group vs. 72% in the placebo group; relative rate 1.05, 95% confidence interval 1.00 to 1.12; p  = 0.07); and three or more (72% in the progesterone group vs. 57% in the placebo group; relative rate 1.28, 95% confidence interval 1.08 to 1.51; p  = 0.004). A significant post hoc subgroup effect (interaction test p  = 0.01) was identified in the subgroup of participants with early pregnancy bleeding and any number of previous miscarriage(s) (75% in the progesterone group vs. 70% in the placebo group; relative rate 1.09, 95% confidence interval 1.03 to 1.15; p  = 0.003). There were no significant differences in the rate of adverse events between the groups. The results of the health economics analysis show that progesterone was more costly than placebo (£7655 vs. £7572), with a mean cost difference of £83 (adjusted mean difference £76, 95% confidence interval -£559 to £711) between the two arms. Thus, the incremental cost-effectiveness ratio of progesterone compared with placebo was estimated as £3305 per additional live birth at ≥ 34 weeks of gestation., Conclusions: Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with threatened miscarriage overall, but an important subgroup effect was identified. A conclusion on the cost-effectiveness of the PRISM trial would depend on the amount that society is willing to pay to increase the chances of an additional live birth at ≥ 34 weeks. For future work, we plan to conduct an individual participant data meta-analysis using all existing data sets., Trial Registration: Current Controlled Trials ISRCTN14163439, EudraCT 2014-002348-42 and Integrated Research Application System (IRAS) 158326., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 24, No. 33. See the NIHR Journals Library website for further project information., Competing Interests: Jane P Daniels declares membership of the Clinical Trials Unit Standing Advisory Committee. Meenakshi Choudhary declares membership of Health Technology Assessment (HTA) Maternal, Newborn and Child Health (MNCH) Panel and the HTA Prioritisation Committee. Jane E Norman declares membership of the HTA MNCH Panel, that she currently receives funding from the National Institute for Health Research Efficacy and Mechanism Evaluation (EME) programme, that she participates in a Data Monitoring and Ethics Committee for GlaxoSmithKline plc (Brentford, UK) and that she is a paid consultant for Dilafor AB (Solna, Sweden). She was a member of the HTA and EME Editorial Board from 2012 to 2014. Caroline Overton declares that she was a Mylan clinical educator for general practitioner education about hormone replacement therapy and incorporated private practice in April 2017 (now called Bristol Women’s Clinic Ltd).

Objectives: To assess the cost-effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding., Design: Economic evaluation alongside a large multi-centre randomised placebo-controlled trial., Setting: Forty-eight UK NHS early pregnancy units., Population: Four thousand one hundred and fifty-three women aged 16-39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac., Methods: An incremental cost-effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages., Main Outcome Measures: Cost per additional live birth at ≥34 weeks of gestation., Results: Progesterone intervention led to an effect difference of 0.022 (95% CI -0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI -£559 to £711) more than the mean cost in the placebo group. The incremental cost-effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014-0.096) and this was associated with a cost saving of £322 (95% CI -£1318 to £673)., Conclusions: The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost-effective intervention, particularly for women with previous miscarriage(s)., Tweetable Abstract: Progesterone treatment is likely to be cost-effective in women with early pregnancy bleeding and a history of miscarriage., (© 2020 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.)

Background: Bleeding in early pregnancy is strongly associated with pregnancy loss. Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone therapy may improve pregnancy outcomes in women who have bleeding in early pregnancy., Methods: We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate progesterone, as compared with placebo, in women with vaginal bleeding in early pregnancy. Women were randomly assigned to receive vaginal suppositories containing either 400 mg of progesterone or matching placebo twice daily, from the time at which they presented with bleeding through 16 weeks of gestation. The primary outcome was the birth of a live-born baby after at least 34 weeks of gestation. The primary analysis was performed in all participants for whom data on the primary outcome were available. A sensitivity analysis of the primary outcome that included all the participants was performed with the use of multiple imputation to account for missing data., Results: A total of 4153 women, recruited at 48 hospitals in the United Kingdom, were randomly assigned to receive progesterone (2079 women) or placebo (2074 women). The percentage of women with available data for the primary outcome was 97% (4038 of 4153 women). The incidence of live births after at least 34 weeks of gestation was 75% (1513 of 2025 women) in the progesterone group and 72% (1459 of 2013 women) in the placebo group (relative rate, 1.03; 95% confidence interval [CI], 1.00 to 1.07; P = 0.08). The sensitivity analysis, in which missing primary outcome data were imputed, resulted in a similar finding (relative rate, 1.03; 95% CI, 1.00 to 1.07; P = 0.08). The incidence of adverse events did not differ significantly between the groups., Conclusions: Among women with bleeding in early pregnancy, progesterone therapy administered during the first trimester did not result in a significantly higher incidence of live births than placebo. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment program; PRISM Current Controlled Trials number, ISRCTN14163439.)., (Copyright © 2019 Massachusetts Medical Society.)

A 36-year-old woman was referred by general practitioner to the early pregnancy unit with pelvic pain in her seventh week of pregnancy. She had a transvaginal ultrasound. Unruptured live twin tubal ectopic pregnancy was diagnosed on. Diagnostic laparoscopy revealed an unruptured left interstitial ectopic pregnancy. The interstitial tubal pregnancy was removed by laparoscopic automatic stapler with minimal blood loss. The patient had an uneventful recovery to health.