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18. Long-acting microneedle formulations

Author

Vora, Lalitkumar K., Sabri, Akmal H., Naser, Yara, Himawan, Achmad, Hutton, Aaron R.J., Anjani, Qonita Kurnia, Volpe-Zanutto, Fabiana, Mishra, Deepakkumar, Li, Mingshan, Rodgers, Aoife M., Paredes, Alejandro J., Larrañeta, Eneko, Thakur, Raghu Raj Singh, and Donnelly, Ryan F.

Published
2023
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20. Solid implantable devices for sustained drug delivery

Author

Magill, Elizabeth, Demartis, Sara, Gavini, Elisabetta, Permana, Andi Dian, Thakur, Raghu Raj Singh, Adrianto, Muhammad Faris, Waite, David, Glover, Katie, Picco, Camila J., Korelidou, Anna, Detamornrat, Usanee, Vora, Lalitkumar K., Li, Linlin, Anjani, Qonita Kurnia, Donnelly, Ryan F., Domínguez-Robles, Juan, and Larrañeta, Eneko

Published
2023
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24. Development of antibiotic microneedle delivery systems for tuberculosis treatment

Author

Anjani, Qonita Kurnia, Donnelly, Ryan, and Larraneta Landa, Eneko

Subjects
616.99, tuberculosis, microneedles, antibiotic, hydrogel, cyclodextrin
Abstract

Current therapy of tuberculosis (TB) has several limitations, such as risk of liver injury and intestinal dysbiosis due to frequent oral administration of antibiotics. Transdermal administration could be used to improve antibiotic delivery for treatment of Mycobacterium tuberculosis infection. Therefore, this thesis described a novel approach, using hydrogel-forming microneedle (MN) arrays to transdermally deliver TB drugs, namely rifampicin, isoniazid, pyrazinamide and ethambutol, which have different physicochemical properties. These drugs were individually prepared into three types of drug reservoirs, including lyophilised tablets, directly compressed tablets and poly(ethylene glycol) tablets. In the specific case of RIF, as the most hydrophobic drug compared to the other three, the inclusion complex between RIF and cyclodextrin was developed. Moreover, formulations of each drug reservoir type were optimised to achieve a rapidly dissolving tablet, and further integrated with hydrogel-forming MN arrays for in vitro permeation studies. Three types of hydrogel formulation were manufactured using different type of polymers and crosslinking processes. These MN arrays were then evaluated in terms of swelling ability, morphology and physical properties. Results of solute diffusion studies showed that drug permeation across the swollen hydrogel membrane was affected mostly by physiochemical properties and functional groups of each drug. In the in vitro studies, the amount of permeated drug through the hydrogel-forming MN arrays across the dermatomed neonatal porcine skin was affected by the drug solubility and reservoir design. The development of this transdermal TB drug regimen is still in the early stage, thus a further investigation to evaluate the effectivity, stability, safety, and efficacy prior to the clinical application will be required. For instance, in vivo pharmacokinetic studies must be done to determine the plasma concentration of the drug in the animal model. Besides, to ensure the efficacy of this system, pharmacodynamic studies must be also performed. On this basis, to reach clinical practice and ensure the benefit for TB treatment application, this novel approach should be tested in terms of the usability and acceptability to achieve the maximum impact of this work.

Published
2020

40. Novel SmartReservoirs for hydrogel-forming microneedles to improve the transdermal delivery of rifampicin.

Author

Abraham, Abraham M., Anjani, Qonita Kurnia, Adhami, Masoud, Hutton, Aaron R. J., Larrañeta, Eneko, and Donnelly, Ryan F.

Abstract

Hydrogel-forming microneedles (HF-MNs) are composed of unique cross-linked polymers that are devoid of the active pharmaceutical ingredient (API) within the microneedle array. Instead, the API is housed in a reservoir affixed on the top of the baseplate of the HF-MNs. To date, various types of drug-reservoirs and multiple solubility-enhancing approaches have been employed to deliver hydrophobic molecules combined with HF-MNs. These strategies are not without drawbacks, as they require multiple manufacturing steps, from solubility enhancement to reservoir production. However, this current study challenges this trend and focuses on the delivery of the hydrophobic antibiotic rifampicin using SmartFilm-technology as a solubility-enhancing strategy. In contrast to previous techniques, smart drug-reservoirs (SmartReservoirs) for hydrophobic compounds can be manufactured using a one step process. In this study, HF-MNs and three different concentrations of rifampicin SmartFilms (SFs) were produced. Following this, both HF-MNs and SFs were fully characterised regarding their physicochemical and mechanical properties, morphology, Raman surface mapping, the interaction with the cellulose matrix and maintenance of the loaded drug in the amorphous form. In addition, their drug loading and transdermal permeation efficacy were studied. The resulting SFs showed that the API was intact inside the cellulose matrix within the SFs, with the majority of the drug in the amorphous state. SFs alone demonstrated no transdermal penetration and less than 20 ± 4 μg of rifampicin deposited in the skin layers. In contrast, the transdermal permeation profile using SFs combined with HF-MNs (i.e. SmartReservoirs) demonstrated a 4-fold increase in rifampicin deposition (80 ± 7 μg) in the skin layers and a permeation of approx. 500 ± 22 μg. Results therefore illustrate that SFs can be viewed as novel drug-reservoirs (i.e. SmartReservoirs) for HF-MNs, achieving highly efficient loading and diffusion properties through the hydrogel matrix. [ABSTRACT FROM AUTHOR]

Published
2024
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48. Engineering and Development of a Tissue Model for the Evaluation of Microneedle Penetration Ability, Drug Diffusion, Photothermal Activity, and Ultrasound Imaging: A Promising Surrogate to Ex Vivo and In Vivo Tissues (Adv. Mater. 18/2023)

Author

Makvandi, Pooyan, primary, Shabani, Majid, additional, Rabiee, Navid, additional, Anjani, Qonita Kurnia, additional, Maleki, Aziz, additional, Zare, Ehsan Nazarzadeh, additional, Sabri, Akmal Hidayat Bin, additional, De Pasquale, Daniele, additional, Koskinopoulou, Maria, additional, Sharifi, Esmaeel, additional, Sartorius, Rossella, additional, Seyedhamzeh, Mohammad, additional, Bochani, Shayesteh, additional, Hirata, Ikue, additional, Paiva‐Santos, Ana Cláudia, additional, Mattos, Leonardo S., additional, Donnelly, Ryan F., additional, and Mattoli, Virgilio, additional

Published
2023
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49. Poly(caprolactone)/Lignin-based 3D-printed Dressings Loaded with a Novel Combination of Bioactive Agents for Wound-healing Applications

Author

Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica, Wellcome Trust. UK., Domínguez Robles, Juan, Cuartas Gómez, Elías, Dynes, Sean, Utomo, Emilia, Anjani, Qonita Kurnia, Detamornrat, Usanee, Donnelly, Ryan F., Moreno Castellanos, Natalia, Larrañeta, Eneko, Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica, Wellcome Trust. UK., Domínguez Robles, Juan, Cuartas Gómez, Elías, Dynes, Sean, Utomo, Emilia, Anjani, Qonita Kurnia, Detamornrat, Usanee, Donnelly, Ryan F., Moreno Castellanos, Natalia, and Larrañeta, Eneko

Abstract

Curcumin (CUR) has been shown to possess significant anti-inflammatory properties and significant wound healing potential. Additionally, lignin (LIG) is a renewable biomacromolecule with well-known antioxidant and antimicrobial properties, which makes this biomacromolecule a good candidate to be included in medical materials, such as wound dressings. Although many of the wound dressings used at present have interesting features, some are limited in terms of antibacterial properties. To address these limitations, in the present work, both CUR and LIG were combined with poly(caprolactone) (PCL), a biocompatible polymer, to obtain dressings with antioxidant and antimicrobial properties for wound healing treatment. Moreover, D-Panthenol (DPA) was included in the composite materials formulation due to its skin regenerative ability by enhancing epidermal differentiation. Semi-solid extrusion (SSE) 3D printing was used to manufacture wound dressings without the use of any solvents. 3D-printed dressings provided a sustained DPA and CUR release for periods of up to 4 and 35 days, respectively. A DPPH (2,2-diphenyl-1-picrylhydrozyl) assay was performed confirming that the presence of LIG and CUR provided antioxidant properties to the 3D-printed dressings. Additionally, these 3D-printed materials showed a marked resistance to adherence of Staphylococcus aureus when compared to the PCL control 3D-printed samples, resulting in substantial reductions of up to 89.9% and 98.9% after incubation periods of 4 h and 24 h respectively. Although, all of the 3D-printed materials were able to provide a supportive environment for cellular attachment, viability and growth, the combination of both bioactive compounds CUR and DPA exhibited the most significant values for cell viability and proliferation. In vivo wound healing study performed in Wistar rats showed that dressings containing these novel two compounds CUR and DPA exhibited marked improvement at any stage of the treatment process.

Published
2023

50. Liposome-loaded Polymeric Microneedles for Enhanced Skin Deposition of Rifampicin

Author

Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica, Wellcome Trust, Anjani, Qonita Kurnia, Pandya, Anjali K., Demartis, Sara, Domínguez Robles, Juan, Moreno Castellanos, Natalia, Li, Huanhuan, Gavini, Elisabetta, Patravale, Vandana B., Donnelly, Ryan F., Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica, Wellcome Trust, Anjani, Qonita Kurnia, Pandya, Anjali K., Demartis, Sara, Domínguez Robles, Juan, Moreno Castellanos, Natalia, Li, Huanhuan, Gavini, Elisabetta, Patravale, Vandana B., and Donnelly, Ryan F.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a prevailing bacterial pathogen linked to superficial skin and soft tissue infections (SSTIs). Rifampicin (RIF), a potent antibiotic against systemic and localised staphylococcal infections, faces limitations due to its low solubility. This constraint hampers its therapeutic potential for MRSA-induced SSTIs. To address this, an advanced liposomal system was designed for efficient dermal RIF delivery. Rifampicin-loaded liposomes (LipoRIF) were embedded within polymeric dissolving microneedles (DMNs) to enable targeted intradermal drug delivery. A robust Design of Experiment (DoE) methodology guided the systematic preparation and optimisation of LipoRIF formulations. The optimal LipoRIF formulation integrated within polymeric DMNs. These LipoRIF-DMNs exhibited favourable mechanical properties and effective skin insertion characteristics. Notably, in vitro assays on skin deposition unveiled a transformative result – the DMN platform significantly enhanced LipoRIF deposition within the skin, surpassing LipoRIF dispersion alone. Moreover, LipoRIF-DMNs displayed minimal cytotoxicity toward cells. Encouragingly, rigorous in vitro antimicrobial evaluations demonstrated LipoRIF-DMNs' capacity to inhibit MRSA growth compared to the control group. LipoRIF-DMNs propose a potentially enhanced, minimally invasive approach to effectively manage SSTIs and superficial skin ailments stemming from MRSA infections.

Published
2023

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