Having started my career in pharmaceutical industry, my research focuses on the control and use of solid-state forms of API. The solid state of API has an important impact on properties of solid drug forms such as tablets, influencing hygroscopicity, biodisponibility. My research focuses on engineering the solid-state of API adding multiple components to the same solid phase. We showed how multi-component crystallization (co-crystallization) can be used to control the solid-state properties of drug compounds (hygroscopicity, melting point stabilization, …)¹ but can be used as well as to expand the patent life-time of a given drug.² In parallel, we also specialize in developing multi-component crystallization processes, upscaling it to the kg scale.³ Doing so, requires a careful control of underlying thermodynamics and kinetics. In a final part of my research, we go one step further, using the specific properties of multi-component systems to develop novel crystallization-based applications. In particular my group has developed a novel type of resolution based on enantiospecific co-crystallization from solution.⁴ We recently expanded this to resolve mandelic acid using preferential co-crystallization.⁵ In our latest ground-breaking work, we used the underlying thermodynamics of these systems, to pull them towards a transformation of the racemate into an enantiopure drug in a so-called deracemization process.⁶

Inventing novel methods for making fine bubbles, particles, capsules and fibres of the micro-nano scale is an essential part of modern advanced science and engineering. These structures play an important part in key areas like healthcare engineering which is of a very high utilitarian value and public demand. Microbubbles are crucial contrast agents in ultrasound imaging, and also very effective in drug delivery. Particles and capsules are extensively used in modern therapeutics. Fibres are used in advanced applications such as tissue engineering, microbial screening and chronic wound healing strategies. However, the quest to make these structures in a reproducible manner with high productivity and process control is still elusive and is a hot topic where scale-up possibilities and actual industrial manufacturing are crucial factors. The Biomaterials Processing & Forming Laboratory (www.edirisinghelab.com) has been at the forefront of this research and this talk will illustrate how these novel making developments are currently taking place at great pace. This work has led to many inventions and has won over 20 high impact factor international journal front covers. For example, microbubble generation using microfluidics and electrohydrodynamics and their combination has led to a new medical frontier (1), we are the inventors of the combined method. We have also invented new electrohydodynamic devices which can make 4-layered particles (2) and these are paving the way to a new generation of therapeutics, for example to combat urinary tract infections in a new way. We have invented a new fibre manufacturing method called pressurised gyration (3) which has allowed doped-manufacturing of polymeric fibres with a high yield and this has revolutionized fibre-mesh generation for making antimicrobial filtration mats, tissue engineering constructs and wound healing and drug delivery patches. Our work has also paved new ways of utilising graphene and its derivatives in biomedical engineering (4). More exciting developments are in progress in collaboration with USA, China and Europe to further harness these manufacturing technologies especially in biotechnology (5) and core-sheath structure generation to enhance biomedical applications (6) and this talk will briefly indicate the exciting progress we are making in these areas.

References

1. M.Edirisinghe and S.Dalvi, Langmuir, 2019, Volume 35, Issue 31 (special issue), pages 9995-10222
2. S.Labbaf, H.Ghanbar, E.Stride and M.Edirisinghe, Macromol Rapid Commun. 2014; 35(6), 618–623.
3. P.Heseltine, J.Ahmed and M.Edirisinghe, Macromol Mater. & Eng., 2018, Vol. 303((9), 1800218.
4. M.Edirisinghe, The Royal Society Interface Focus, Special Issue, April 2018, Vol. 8, issue 3.
5. J.Ahmed, M.Gultekinoglu and M.Edirisinghe, Biotech. Adv., 2020, Volume 41, July-August issue, 107549.
6. S.Mahalingam, R.Matharu, S.Homer-Vanniasinkam and M.Edirisinghe, Appl. Phys. Rev., 2020, 7, 041302 .

This presentation focuses on the solid-state structures of cyclodextrins (CDs) and their inclusion complexes with medicinally relevant guest compounds, with emphasis on the wide variety of observed modes of inclusion of drug molecules in CDs and the nature of CD complex packing features. As revealed by X-ray diffraction studies on single crystals of different CD-drug complexes, the inclusion modes may span the entire range from complete guest encapsulation within the hydrophobic cavities of the macrocyclic CD host molecules to extra-cavity guest location where they are in contact with only the external surfaces of neighbouring CD molecules. Additional structural variations arise from the presence of varying amounts and variable locations of water molecules in CD-drug complexes (a common occurrence) and frequent instances of spatial guest molecule disorder, which can be severe. Each crystalline CD-drug complex is thus structurally unique and consequently displays distinct pharmaceutically relevant properties. This emphasises the need for rigorous control in the preparation and characterization of the desired crystalline phase to ensure reproducible performance in a pharmaceutical application. Single crystal X-ray diffraction (SCXRD) and powder X-ray diffraction (PXRD) are invaluable complementary techniques for achieving the important goal of definitive identification of the desired phase, as will be illustrated in the presentation. Furthermore, the detailed crystal structures of representative CD complexes containing bioactive guest molecules from several classes of drugs and other bioactive compounds (e.g. antioxidants, anti-inflammatories, anticancer agents, anticonvulsants, antimalarials) will be described. Other significant aspects of crystalline CD complexes that will be highlighted include ‘polymorphism’ and the frequent occurrence of ‘isostructural’ CD host molecule assemblies in a series of complexes with a common host but different guest molecules. These ‘inversely-related’ solid-state phenomena have important implications for the physicochemical properties and the systematic structural classification of CD complexes.

Background: The use of hydrogels in the treatment of wound healing is becoming an increasingly routine. Hydrogels are materials that protect wound healing, avoiding and/or controlling infection, and providing moisture for the irregular wound environment. Poloxamer 407 (P407), chitosan (CH) and hyaluronic acid (HA) are biomaterials investigated to promote wound repair. P407 has thermoreversible properties and promotes wound contraction¹. CH presents inherent analgesic, hemostatic and microbial effects². HA, interacts directly with cells through its cell surface receptors resulting in fibroblast proliferation and protein synthesis³.

Purpose: The aim of this work was to develop and characterize a hydrogel (HG) prepared from a physical mixture of P407, CH and AH for the treatment of skin and mucosal wounds.

Methods: 0.5% CTS was dispersed in 0.5% acetic acid. Previously prepared 0.2% HA solution was added to the previous solution. The final HG was made by adding P407 (18 %) using the cold method with continuous stirring for 24 h. The HG was characterized by the following methods: swelling test, microbiological and in vivo studies. Swelling rate was assessed by a gravimetric method in phosphate buffer saline (PBS) at 32 ± 0.5 ºC for pH 5.5 and 37 ± 0.5 ºC for pH 7.4. The antimicrobial activity was evaluated through a Kirby-Bauer Disk Diffusion Susceptibility Test⁴ against Gram-negative bacteria, Gram-positive bacteria and fungi. The wound healing efficacy of the HG was evaluated in burn inducted mice. The formulation was applied topically once a day during 14 days. 2 groups were evaluated, hydrogel and reference formulation.

Results and Discussion: The swelling behavior in wound healing could help to absorb exudates and provides mechanical resiliency to the delivery system at the biological site of action⁴. Our results showed high swelling rates, being the best value at pH = 5.5. The HG provides an important improvement on antimicrobial properties and showed similar activity to reference. The wound healing in animals treated with HG was similar to Silvederma^®.

Conclusions: The HG exhibited important antimicrobial and biological effects. Thus this hydrogel could be proposed as a suitable vehicle for new therapies for wound healing and infections on skin and mucosa.

References:

¹Leyva-Gómez et al. Materials Science and Engineering C 74: 36-46, 2017.

² Zhao X. et al. Biomaterials, 122:34-47, 2017.

³Hodgkinson and Bayat. J Appl Biomater Funct Mater 14(1): e9-e18, 2016.

⁴Gao et al. Colloids Surf. B Biointerfaces 167: 448–456, 2018.