Sage Journals: Discover world-class research

Abstract

In this study, we explored the design of polymeric nanocapsules as vehicles for controlled release of iron. Amphiphilic block copolymers (ABCs) composed of polyethylene glycol (PEG) and poly (ε-caprolactone) (PCL) segments were synthesized via ring-opening polymerization (ROP), using PEG and methoxy-PEG (mPEG) with varying molecular weights as macroinitiators. Structural and molecular characterizations using infrared spectroscopy, proton nuclear magnetic resonance and gel permeation chromatography confirmed successful copolymerization and narrow dispersity indices (Ð <1.5). Iron-loaded nanocapsules were formulated using the double emulsion solvent evaporation (DESE) technique with synthesized PEG-b-PCL copolymers as polymeric precursors. The impact of the copolymer composition on the particle size, morphology, and encapsulation efficiency (EE%) was evaluated. Spherical nanocapsules with diameters below 500 nm were obtained, and a positive correlation was observed between copolymer molecular weight and EE%, with the highest value (74.4%) achieved for the Fe@COP5-96 formulation. Differential scanning calorimetry (DSC) analysis revealed that iron incorporation altered the thermal behavior of the copolymers, resulting in a shift of the melting peaks toward lower temperatures and a decrease in melting enthalpy, consistent with reduced crystallinity arising from ion–polymer interactions. The iron release kinetics exhibited a sustained release behavior. These results demonstrate the potential of PEG-b-PCL nanocapsules as effective carriers for ionic species with promising applications in nutrient delivery and medical therapies.

Keywords

iron encapsulation PEG-b-PCL copolymers polymeric nanocapsules and controlled release

Get full access to this article

View all access options for this article.

References

Shumoy

Raes

. Dissecting the facts about the impact of contaminant iron in human nutrition: a review. Trends Food Sci Technol 2021; 116: 918–927.

Gayen

Kumar

Rawat

. A study on the of nutrition, health and hygiene counselling impact on iron deficiency anaemia. J Adv Sch Res Allied Educ 2024; 21(1): 226–231.

Sun

Tan

Zhang

, et al. Iron deficiency anemia: a critical review on iron absorption, supplementation and its influence on gut microbiota. Food Funct 2024; 15(3): 1144–1157.

Hallberg

Hulthén

. Prediction of dietary iron absorption: an algorithm for calculating absorption and bioavailability of dietary iron. Am J Clin Nutr 2000; 71(5): 1147–1160.

Zijp

Korver

Tijburg

LBM

. Effect of tea and other dietary factors on iron absorption. Crit Rev Food Sci Nutr 2000; 40(5): 371–398.

Michalak

. Iron deficiency anemia–new possibilities of iron supplementation in various clinical conditions. Acta Haematol Pol 2020; 51(4): 212–219.

Dixon

Lemberg

Lamprecht

, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 2012; 149(5): 1060–1072.

Radulescu

Brookes

Salgueiro

, et al. Luminal iron levels govern intestinal tumorigenesis after Apc loss in vivo. Cell Rep 2012; 2(2): 270–282.

Ebea-Ugwuanyi

Vidyasagar

Connor

, et al. Oral iron therapy: current concepts and future prospects for improving efficacy and outcomes. Br J Haematol 202 ; 204: 759–773.

10.

Zakrzewski

Wilkins

Helman

, et al. Supplementation with sucrosomial® iron leads to favourable changes in the intestinal microbiome when compared to ferrous sulfate in mice. Biometals 2022; 35(1): 27–38.

11.

Bloor

Schutte

Hobson

. Oral iron supplementation—gastrointestinal side effects and the impact on the gut microbiota. Microbiol Res 2021; 12: 491–502, Page Press Publication.

12.

Fathi

Martín

McClements

. Nanoencapsulation of food ingredients using carbohydrate based delivery systems. In: Trends in food science and technology. Elsevier Ltd, 2014, pp. 18–39.

13.

Yuan

Chen

, et al. Enhanced oral bioavailability and tissue distribution of ferric citrate throughliposomal encapsulation. CyTA--J Food 2017; 15(1): 1–7.

14.

Dehnad

Ghorani

Emadzadeh

, et al. Recent advances in iron encapsulation and its application in food fortification. Crit Rev Food Sci Nutr 2024; 64(33): 12685–12701.

15.

Churio

Durán

Guzmán-Pino

, et al. Use of encapsulation technology to improve the efficiency of an iron oral supplement to prevent anemia in suckling pigs. Animals 2019; 9(1): 9010001.

16.

Patel

Zariwala

Al-Obaidi

. Fabrication of biopolymer based nanoparticles for the entrapment of chromium and iron supplements. Processes 2020; 8(6): 707.

17.

Zariwala

Elsaid

Jackson

, et al. A novel approach to oral iron delivery using ferrous sulphate loaded solid lipid nanoparticles. Int J Pharm 2013; 456(2): 400–407.

18.

Iqbal

Valour

Fessi

, et al. Preparation of biodegradable PCL particles via double emulsion evaporation method using ultrasound technique. Colloid Polym Sci 2015; 293(3): 861–873.

19.

Piñón-Segundo

Nava-Arzaluz

Lechuga-Ballesteros

. Pharmaceutical polymeric nanoparticles prepared by the double emulsion-solvent evaporation technique. Recent Pat Drug Deliv Formulation 2012; 6(3): 224–235.

20.

Khoee

Yaghoobian

. An investigation into the role of surfactants in controlling particle size of polymeric nanocapsules containing Penicillin-G in double emulsion. Eur J Med Chem 2009; 44(6): 2392–2399.

21.

Posada

Sierra

Perez

. An evaluation of the effect of reaction conditions in the enzymatically catalyzed synthesis of poly (Ε‐Caprolactone). ChemistrySelect 2022; 7(37): e202202372.

22.

Angarita

Umaña-Perez

Perez

. Enhancing the performance of PEG-b-PCL-Based nanocarriers for curcumin through its conjugation with lipophilic biomolecules. J Bioact Compat Polym 2020; 35(4–5): 399–413.

23.

Arias

Angarita-Villamizar

Baena

, et al. Phospholipid-conjugated PEG-b-PCL copolymers as precursors of micellar vehicles for amphotericin B. Polymers 2021; 13(11): 1747.

24.

Moreno

Forero

Baena

, et al. Co-Encapsulation of curcumin and salicylic acid in mucoadhesive polymer nanoparticles. J Appl Pharmaceut Sci 2024; 14(1): 189–196.

25.

Vakh

Freze

Pochivalov

, et al. Simultaneous determination of iron (II) and ascorbic acid in pharmaceuticas based on flow sandwich technique. J Pharmacol Toxicol Methods 2015; 73: 56–62.

26.

Mohanty

Jana

Manna

, et al. Synthesis and evaluation of MePEG-PCL diblock copolymers: surface properties and controlled release behavior. Prog Biomater 2015; 4(2–4): 89–100.

27.

Villamil

Parra-Giraldo

Pérez

. Enhancing the performance of PEG-b-PCL copolymers as precursors of micellar vehicles for amphotericin B through its conjugation with cholesterol. Colloids Surf A Physicochem Eng Asp. 2019; 572: 79–87.

28.

Diaz

Sierra

Jérôme

, et al. Target grafting of Poly(2-(Dimethylamino)Ethyl methacrylate) to biodegradable block copolymers. J Polym Sci 2020; 58(16): 20200204.

29.

Faisal

Clulow

MacWilliams

, et al. Microstructure—thermal property relationships of poly (Ethylene Glycol-b-Caprolactone) copolymers and their micelles. Polymers 2022; 14(20): 4365.

30.

Garg

Vakili

Lavasanifar

. Polymeric micelles based on Poly(Ethylene oxide) and α-Carbon substituted Poly(ɛ-Caprolactone): an in vitro study on the effect of core forming block on polymeric micellar stability, biocompatibility, and immunogenicity. Colloids Surf B Biointerfaces 2015; 132: 161–170.

31.

Ibraheem

Iqbal

Agusti

, et al. Effects of process parameters on the colloidal properties of polycaprolactone microparticles prepared by double emulsion like process. Colloids Surf A Physicochem Eng Asp 2014; 445: 79–91.

32.

Feczkó

Tóth

Dósa

, et al. Influence of process conditions on the mean size of PLGA nanoparticles. Chem Eng Process Process Intensif 2011; 50(8): 846–853.

33.

Hill

Doane

, et al. Electrophoretic interpretation of PEGylated NP structure with and without peripheral charge. Langmuir 2015; 31(37): 10246–10253.

34.

Gref

Lück

Quellec

, et al. Stealth’ corona-core nanoparticles surface modified by polyethylene glycol (PEG): Influences of the Corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. Colloids Surf B Biointerfaces 2000; 18(3): 301–313.

35.

D’Angeli

Granata

Romano

, et al. Biocompatible Poly(ε-Caprolactone) nanocapsules enhance the bioavailability, antibacterial, and immunomodulatory activities of curcumin. Int J Mol Sci 2024; 25(19): 10692.

36.

Zhao

Wang

Yang

, et al. Stability of electrostatically stabilized pickering emulsion of Silica particles and soy hull polysaccharides: mechanism of PH and ionic strength. Food Chem 2025; 471: 142804.

37.

Lee

Kim

, et al. Poly(Butylene Terephthalate)/Poly(Ethylene Glycol) blends with compatibilizers. J Appl Polym Sci 2024; 141(15): e55230.

38.

Sun

Deng

, et al. Study of the synthesis, crystallization, and morphology of poly(ethylene glycol)-poly(epsilon-caprolactone) diblock copolymers. Biomacromolecules 2004; 5(5): 2042–2047.

39.

Huang

Wang

R-Y

Tong

Z-Z

, et al. Influence of ionic species on the microphase separation behavior of PCL-b-PEO/Salt hybrids. Macromolecules 2014; 47(23): 8359–8367.

40.

Zheng

Yang

, et al. Modulation of ion transport in nanopores using polyethylene glycol. Langmuir 2024; 40(50): 26742–26750.

41.

Korsmeyer

Gurny

Doelker

, et al. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 1983; 15(1): 25–35.

42.

Almasri

Dahman

. Bioactive glass preloaded with antibiotics for delivery of long-term localized drug release exhibiting inherent antimicrobial activity. Appl Sci 2025; 15(10): 5363.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.13 MB