Yingchang Ma

All Publications

• In-situ hyaluronic acid-tyramine hydrogels prolong the release of extracellular vesicles and enhance stability. International journal of pharmaceutics Ma, Y., Colic, I., Muwaffak, M., Rahim, A. A., Brocchini, S., Williams, G. R. 2025: 125650

  Abstract

  Hydrogels can provide a hydrated environment to encapsulate extracellular vesicles (EVs) while offering promising solutions to some of the challenges that limit their therapeutic potential, e.g. rapid clearance and propensity for enzymatic degradation and aggregation. This study explores the use of a hyaluronic acid-tyramine (HA-TA) hydrogel to prolong the delivery and enhance the stability of EVs. EVs were obtained from lentiviral-transduced HEK293T cells expressing luciferase and eGFP to enable easy quantification. Two encapsulation strategies were evaluated: (1) pre-loading, where EVs were mixed with HA-TA (2.58 % degree of substitution) precursor solution and subsequently crosslinked with 2 U/mL horseradish peroxidase (HRP) and 0.05 mM H2O2; and (2) post-loading, where EVs were soaked into pre-formed dehydrated hydrogels. Both methods improved EV stability over 7 days at 37 °C compared to free EVs. The pre-loading approach was ultimately selected due to its ability to give rapid in situ gelation within one minute. Controlled in vitro release of EVs from the pre-loaded hydrogels was observed to extend beyond 7 days, as determined by CD9 ELISA. The released EVs maintained their bioactivity, as evidenced by effective internalisation into ARPE-19 and H9c2 cell lines, with performance comparable to fresh EVs. The EV release profile could be varied by modifying the hydrogel concentration. These findings underscore the potential of HA-TA hydrogels for localised, sustained, EV delivery with preserved functionality.

  View details for DOI 10.1016/j.ijpharm.2025.125650

  View details for PubMedID 40311824

• Development of hyaluronic acid/β-cyclodextrin semi-interpenetrating network hydrogels for prolonged delivery of water-soluble sunitinib malate. International journal of pharmaceutics Ma, Y., Yu, Z., Waudby, C. A., Ju, T., Zhou, X., Brocchini, S., Williams, G. R. 2025; 669: 125039

  Abstract

  Sunitinib malate (SUM), widely used in cancer treatment for its anti-VEGF properties, has also been explored for ocular neovascular diseases. For ocular applications, sustained drug release is essential to reduce dosing frequency. Hyaluronic acid (HA)-based hydrogels are commonly used for controlled drug delivery, but their hydrophilicity leads to rapid drug diffusion, especially for water-soluble drugs like SUM. To address this, β-cyclodextrin (β-CD) polymers (2-300 kDa) were incorporated into tyramine-conjugated HA (HA-TA) (200-400 kDa) networks to extend drug release via the formation of host-guest inclusion complexes. SUM-CD intermolecular interactions were identified and characterised by 1H NMR and FTIR spectroscopies, and NOESY spectra further confirmed a 1 SUM: 2 β-CD inclusion complex. β-CD polymers (10 % w/v) were integrated into HA-TA (0.25, 0.5, 1 % w/v) networks enzymatically crosslinked using horseradish peroxidase and hydrogen peroxide, forming semi-interpenetrating polymer network hydrogels. These gels exhibited faster gelation, enhanced swelling behaviour, higher drug loading capacity, a denser matrix, and a longer SUM release duration compared to HA-TA hydrogels. In an in vitro flow model, post-gelation loading of SUM led to a longer release duration than pre-loading, with release continuing over 20 days. The HA-CD semi-IPN hydrogel therefore warrants further exploration for its potential ocular applications.

  View details for DOI 10.1016/j.ijpharm.2024.125039

  View details for PubMedID 39662858

• Extracellular vesicle-embedded materials. Journal of controlled release : official journal of the Controlled Release Society Ma, Y., Brocchini, S., Williams, G. R. 2023; 361: 280-296

  Abstract

  Extracellular vesicles (EVs) are small membrane-bound vesicles released by cells. EVs are emerging as a promising class of therapeutic entity that could be adapted in formulation due to their lack of immunogenicity and targeting capabilities. EVs have been shown to have similar regenerative and therapeutic effects to their parental cells and also have potential in disease diagnosis. To improve the therapeutic potential of EVs, researchers have developed various strategies for modifying them, including genetic engineering and chemical modifications which have been examined to confer target specificity and prevent rapid clearance after systematic injection. Formulation efforts have focused on utilising hydrogel and nano-formulation strategies to increase the persistence of EV localisation in a specific tissue or organ. Researchers have also used biomaterials or bioscaffolds to deliver EVs directly to disease sites and prolong EV release and exposure. This review provides an in-depth examination of the material design of EV delivery systems, highlighting the impact of the material properties on the molecular interactions and the maintenance of EV stability and function. The various characteristics of materials designed to regulate the stability, release rate and biodistribution of EVs are described. Other aspects of material design, including modification methods to improve the targeting of EVs, are also discussed. This review aims to offer an understanding of the strategies for designing EV delivery systems, and how they can be formulated to make the transition from laboratory research to clinical use.

  View details for DOI 10.1016/j.jconrel.2023.07.059

  View details for PubMedID 37536545

• Development of a UPLC-TQ/MS Approach for the Determination of Eleven Bioactive Components in Haizao Yuhu Decoction Plus-Minus Haizao and Gancao Drug Combination after Oral Administration in a Rat Model of Hypothyroidism. Molecules (Basel, Switzerland) Ma, Y., Zhang, Y., Zhai, Y., Zhu, Z., Pan, Y., Qian, D., Su, S., Fan, X., Duan, J. 2016; 22 (1)

  Abstract

  Haizao Yuhu Decoction (HYD) has been used for approximately 500 years and is well-known in Traditional Chinese Medicine for its efficacy in the treatment of thyroid-related diseases. In this study, a rapid liquid chromatography-tandem mass spectrometry method was developed for the determination of liquiritin, naringin, hesperidin, peimine, liquiritigenin, glycyrrhizic acid, bergapten, nobiletin, osthole, and glycyrrhetinic acid in rat plasma to investigate the pharmacokinetic profile of different HYD prescriptions in a rat model of hypothyroidism. The differences in pharmacokinetic parameters among the groups were compared by Student's t-test. The pharmacokinetic profile of liquiritin, naringin, hesperidin, peimine, liquiritigenin, glycyrrhizic acid, bergapten, nobiletin, osthole, and glycyrrhetinic acid showed significant differences between Haizao and Gancao anti-drug combination and other herbs in HYD. These results may contribute to the rational clinical use of HYD and reveal the compatibility profile of the Haizao and Gancao anti-drug combination.

  View details for DOI 10.3390/molecules22010007

  View details for PubMedID 28025523

  View details for PubMedCentralID PMC6155732