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Folic Acid Conjugated Nanocarriers for Efficient Targetability and Promising Anticancer Efficacy for Treatment of Breast Cancer: A Review of Recent Updates

Choudhury H, Pandey M, Wen LP, Cien LK, Xin H, Yee ANJ, et al.

Curr Pharm Des, 2020;26(42):5365-5379.
PMID: 32693762 DOI: 10.2174/1381612826666200721000958

Breast cancer (BC) is the commonest cause of cancer deaths among Women. It is known to be caused due to mutations in certain receptors, viz. estrogens or progesterones. The most frequently used conventional treatment strategies against BC include chemotherapy, radiation therapy, and partial or entire mastectomy, however, these strategies are often associated with multiple adverse effects, thus reducing patient compliance. Advancement of nanotechnology in the medical application has been made to enhance the therapeutic effectiveness with a significant reduction in the unintended side-effects associated with incorporated anticancer drugs against cancer. The surface engineering technology of the nanocarriers is more pronounced in delivering the therapeutics specifically to target cells. Consequently, folic acid, a small molecular ligand for the folate receptor overexpressed cells, has shown immense response in treating BC cells. Folic acid conjugated nanocarriers have shown remarkable efficiency in targeting overexpressed folate receptors on the surface of BC cells. Binding of these target-specific folate-conjugated nanocarriers substantially improves the internalization of chemotherapeutics in BC cells, without much exposing the other parts of the body. Simultaneously, these folate-- conjugated nanocarriers provide imaging for regular monitoring of targeted drug delivery systems and their responses to an anticancer therapy. Therefore, this review demonstrates the potential of folate-conjugated nanotherapeutics for the treatment and theranostic approaches against BC along with the significant challenges to anticancer therapy, and the prospective insights into the clinical importance and effectiveness of folate conjugate nanocarriers.

Matched MeSH terms: Folic Acid/therapeutic use
Images of interest. Gastrointestinal: tropical sprue

Rajendra S, Dharnal HK

J Gastroenterol Hepatol, 2004 Sep;19(9):1083.
PMID: 15304129
Matched MeSH terms: Folic Acid/therapeutic use
Characteristics of pregnant women with diabetes using injectable glucose-lowering drugs in the EVOLVE study

Mathiesen ER, Ali N, Anastasiou E, Cypryk K, de Valk HW, Dores JM, et al.

J Matern Fetal Neonatal Med, 2022 Dec;35(25):7992-8000.
PMID: 34182866 DOI: 10.1080/14767058.2021.1940132

AIMS: To examine clinical parameters, glycemic control, folic acid supplementation, and the presence of other chronic diseases during early pregnancy in the EVOLVE study population (women with pre-existing diabetes treated with injectable glucose-lowering drugs).
METHODS: Cross-sectional baseline evaluation of EVOLVE: an international, multicenter, non-interventional study investigating the safety of injectable glucose-lowering drugs in pregnant women with pre-existing type 1 (T1D) or type 2 diabetes (T2D). Data were collected at enrollment visit interviews before gestational week 16.
RESULTS: In total, 2383 women from 17 mainly European countries were enrolled in the study: 2122 with T1D and 261 with T2D; mean age was 31 and 33 years, and duration of diabetes was 15 and 6 years, respectively. For women with T1D or T2D, 63% and 75%, respectively, received basal and rapid-acting insulin, 36% and 3% rapid-acting insulin only, 0.7% and 14.0% basal insulin only, 0.2% and 5.4% premix insulin, 0.0% and 1.2% injectable glucagon-like peptide-1 receptor agonist treatment without insulin. In women with T1D or T2D, respectively, during early pregnancy, 59% and 62% had HbA1c <7.0% (53 mmol/mol); 16% and 36% reported not taking folic acid before or during early pregnancy. Overall, >40% of women had ≥1 chronic concomitant condition (predominantly thyroid disease or hypertension). Retinopathy was the most commonly reported diabetic complication. The most commonly reported previous pregnancy complication was miscarriage.
CONCLUSIONS: Baseline data from this large multinational population of women with pre-existing diabetes indicate that sub-optimal glycemic control, poor pregnancy planning, and chronic concomitant conditions were common in early pregnancy.

Matched MeSH terms: Folic Acid/therapeutic use
Fulltext The Protective Effect of Maternal Folic Acid Supplementation on Childhood Cancer: A Systematic Review and Meta-analysis of Case-control Studies

Wan Ismail WR, Abdul Rahman R, Rahman NAA, Atil A, Nawi AM

J Prev Med Public Health, 2019 Jul;52(4):205-213.
PMID: 31390683 DOI: 10.3961/jpmph.19.020

OBJECTIVES: Maternal folic acid supplementation is considered mandatory in almost every country in the world to prevent congenital malformations. However, little is known about the association of maternal folic acid intake with the occurrence of childhood cancer. Hence, this study aimed to determine the effects of maternal folic acid consumption on the risk of childhood cancer.
METHODS: A total of 158 related articles were obtained from PubMed, Google Scholar, Scopus, and ProQuest using standardized keywords, of which 17 were included in the final review.
RESULTS: Eleven of the 17 articles showed a significant protective association between maternal folic acid supplementation and childhood cancer. Using a random-effects model, pooled odds ratios (ORs) showed a protective association between maternal folic acid supplementation and childhood acute lymphoblastic leukaemia (OR, 0.75; 95% confidence interval [CI], 0.66 to 0.86). However, there was no significant association between maternal folic acid supplementation and acute myeloid leukaemia (OR, 0.70; 95% CI, 0.46 to 1.06) or childhood brain tumours (OR, 1.02; 95% CI, 0.88 to 1.19).
CONCLUSIONS: Maternal folic acid supplementation was found to have a protective effect against childhood acute lymphoblastic leukaemia. Thus, healthcare professionals are recommended to provide regular health education and health promotion to the community on the benefits of folic acid supplementation during pregnancy.

Matched MeSH terms: Folic Acid/therapeutic use
Fulltext Real-world experiences of folic acid supplementation (5 versus 30 mg/week) with methotrexate in rheumatoid arthritis patients: a comparison study

Koh KT, Teh CL, Cheah CK, Ling GR, Yong MC, Hong HC, et al.

Reumatismo, 2016 Sep 09;68(2):90-6.
PMID: 27608797 DOI: 10.4081/reumatismo.2016.872

The objective of this study was to compare the tolerability of methotrexate in two different regimes of folic acid (FA) supplementation in rheumatoid arthritis (RA). We performed a multicenter, cross-sectional observational cohort study on 240 RA patients with 120 patients each in 5 mg of FA weekly and 30 mg of FA weekly supplementation. There were no significant differences for side effects (14.2 versus 22.5%, P=0.523) and discontinuation of methotrexate (3.6 versus 13.3%, P=0.085). RA patients given 5 mg of FA weekly supplementation had a lower disease activity score 28 compared to 30 mg of FA weekly supplementation [3.44 (1.10) versus 3.85 (1.40), P=0.014]. FA supplementation of 5 mg per week and 30 mg per week was associated with similar tolerability of methotrexate in RA patients.

Matched MeSH terms: Folic Acid/therapeutic use*
Chitosan-Carboxymethyl-5-Fluorouracil-Folate Conjugate Particles: Microwave Modulated Uptake by Skin and Melanoma Cells

Nawaz A, Wong TW

J Invest Dermatol, 2018 11;138(11):2412-2422.
PMID: 29857069 DOI: 10.1016/j.jid.2018.04.037

5-Fluorouracil delivery profiles in the form of chitosan-folate submicron particles through skin and melanoma cells in vitro were examined using microwaves as the penetration enhancer. The in vivo pharmacokinetic profile of 5-fluorouracil was also determined. Chitosan-carboxymethyl-5-fluorouracil-folate conjugate was synthesized and processed into submicron particles by spray-drying technique. The size, zeta potential, morphology, drug content, and drug release, as well as skin permeation and retention, pharmacokinetics, in vitro SKMEL-28 melanoma cell line cytotoxicity, and intracellular trafficking profiles of drug/particles, were examined as a function of skin/melanoma cell treatment by microwaves at 2,450 MHz for 5 + 5 minutes. The level of skin drug/particle retention in vitro and in vivo increased in skin treated by microwaves. This was facilitated by the drug conjugating to chitosan and microwaves fluidizing both the protein and lipid domains of epidermis and dermis. The uptake of chitosan-folate particles by melanoma cells was mediated via lipid raft route. It was promoted by microwaves, which fluidized the lipid and protein regimes of the cell membrane, and this increased drug cytotoxicity. In vivo pharmacokinetic study indicated skin treatment by microwave-enhanced drug retention but not permeation. The combination of microwaves and submicron particles synergized skin drug retention and intracellular drug delivery.

Matched MeSH terms: Folic Acid/therapeutic use*
Fulltext School-administered weekly iron-folate supplements improve hemoglobin and ferritin concentrations in Malaysian adolescent girls

Tee ES, Kandiah M, Awin N, Chong SM, Satgunasingam N, Kamarudin L, et al.

Am J Clin Nutr, 1999 Jun;69(6):1249-56.
PMID: 10357747 DOI: 10.1093/ajcn/69.6.1249

BACKGROUND: Iron deficiency and its consequent anemia constitute the commonest micronutrient deficiency in the world.
OBJECTIVE: We investigated whether long-term, weekly iron-folate supplements administered at school would improve hemoglobin and ferritin concentrations in adolescent girls, including those with mild-to-moderate anemia and hemoglobin concentrations indicating borderline anemia.
DESIGN: Subjects were 266 girls with hemoglobin concentrations of 80-119.9 g/L (group A) and 358 girls with hemoglobin concentrations of 120-130 g/L (group B) who were otherwise healthy. Two hundred sixty-six girls in group A and 268 girls in group B were randomly assigned to receive either 60 or 120 mg Fe plus 3.5 mg folic acid weekly for 22 wk. Ninety of the girls in group B were randomly assigned to receive only 5 mg folic acid weekly. Capillary hemoglobin and plasma ferritin were measured at baseline and after 12 and 22 wk of supplementation.
RESULTS: By the end of the study, 2% of the girls had dropped out and > 96% had taken > or = 20 of the 22 tablets; side effects were minimal. Mean plasma ferritin increased significantly in all iron-supplemented groups, independently of initial hemoglobin values and iron doses. Ferritin concentrations decreased in the girls supplemented with folic acid only. As expected, hemoglobin responses to iron were higher in group A than in group B and increases were positively correlated with initial plasma ferritin. Hemoglobin failed to respond to folate supplementation if initial plasma ferritin concentrations were low. Mean hemoglobin increased significantly and consistently in relation to the length of treatment.
CONCLUSION: Long-term, weekly iron-folate supplementation was found to be a practical, safe, effective, and inexpensive method for improving iron nutrition in adolescent schoolgirls.

Comment in: Picciano MF. Iron and folate supplementation: an effective intervention in
adolescent females. Am J Clin Nutr. 1999 Jun;69(6):1069-70. PubMed PMID:
10357724. https://academic.oup.com/ajcn/article/69/6/1069/4714856

Study site: 3 secondary schools, Samarahan district, Sarawak, Malaysia

Matched MeSH terms: Folic Acid/therapeutic use*
Medication prescribing patterns among chronic kidney disease patients in a hospital in Malaysia

Al-Ramahi R

Saudi J Kidney Dis Transpl, 2012 Mar;23(2):403-8.
PMID: 22382249

To determine the medication prescribing patterns in hospitalized patients with chronic kidney disease (CKD) in a Malaysian hospital, we prospectively studied a cohort of 600 patients in two phases with 300 patients in each phase. The first phase was carried out from the beginning of February to the end of May 2007, and the second phase was from the beginning of March to the end of June 2008. Patients with CKD who had an estimated creatinine clearance ≤ 50 mL/min and were older than 18 years were included. A data collection form was used to collect data from the patients' medical records and chart review. All systemic medications prescribed during hospitalization were included. The patients were prescribed 5795 medications. During the first phase, the patients were prescribed 2814 medication orders of 176 different medications. The prescriptions were 2981 of 158 medications during the second phase. The mean number of medications in the first and second phases was 9.38 ± 3.63 and 9.94 ± 3.78 respectively (P-value = 0.066). The top five used medications were calcium carbonate, folic acid/vitamin B complex, metoprolol, lovastatin, and ferrous sulfate. The most commonly used medication classes were mineral supplements, vitamins, antianemic preparations, antibacterials, and beta-blocking agents. This study provides an overview of prescription practice in a cohort of hospitalized CKD patients and indicates possible areas of improvement in prescription practice.

Matched MeSH terms: Folic Acid/therapeutic use