Review
Chemistry, Medicinal
Tuan Sang Tran, Rajkamal Balu, Srinivas Mettu, Namita Roy Choudhury, Naba Kumar Dutta
Summary: Advancements in material design of smart hydrogels and the rapid development of 3D printing technologies have led to the emergence of 4D printing, a promising platform for controlled drug delivery systems that can adapt and mimic natural physio-mechanical changes over time. This review provides an overview of material innovation, technical approaches, and novel 4D printed structures for drug delivery applications, while discussing existing challenges and future prospects.
Review
Chemistry, Analytical
Sofia Moroni, Luca Casettari, Dimitrios A. Lamprou
Summary: Breast cancer, the second most common cancer worldwide, requires a patient-centered approach due to its heterogeneity. 3D printing and 4D printing technologies show potential in breast cancer management. This review provides an overview of current approaches, discusses the benefits and limitations of these technologies, and outlines future perspectives and challenges.
Review
Engineering, Biomedical
Niels G. A. Willemen, Margaretha A. J. Morsink, Devin Veerman, Classius F. da Silva, Juliana C. Cardoso, Eliana B. Souto, Patricia Severino
Summary: Personalized medicine, which tailors medical treatment to individual characteristics, has gained significant interest since the start of the Precision Medicine Initiative in 2015. The use of 3D and 4D printing techniques in pharmaceutical field has opened up new possibilities for drug delivery systems and personalized medicine, with the first 3D printed drug already being used in clinical settings.
BIO-DESIGN AND MANUFACTURING
(2022)
Article
Pharmacology & Pharmacy
Sofia Moroni, Rachel Bingham, Niamh Buckley, Luca Casettari, Dimitrios A. Lamprou
Summary: Breast-conserving surgery is a common treatment for early-stage breast cancer, but it can lead to local recurrence and breast tissue loss. To address these issues, researchers developed a 4D printed implant loaded with doxorubicin. The implant can change size to fit the tissue cavity and showed significant anti-cancer activity in vitro. This personalized implant has the potential to improve aesthetic outcomes and prevent recurrence of breast cancer.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Instruments & Instrumentation
Valentina Andretto, Annalisa Rosso, Stephanie Briancon, Giovanna Lollo
Summary: Oral delivery is a favored method for delivering active molecules, but challenges like the complexity of colloidal systems and their interaction with biological barriers need to be overcome for precision medicine.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Tarun Agarwal, Irene Chiesa, Marco Costantini, Anna Lopamarda, Maria Celeste Tirelli, Om Prakash Borra, Subhash Venkata Sai Varshapally, Yanamadala Ashwin Vijay Kumar, G. Koteswara Reddy, Carmelo De Maria, Lijie Grace Zhang, Tapas Kumar Maiti
Summary: Tissue engineering research has been greatly improved by the introduction of bioprinting technologies, which allow the development of customized biomaterial inks with excellent printability and cell-promoting abilities. This review focuses on chitosan-based materials as suitable inks for 3D/4D bioprinting, and their applications in drug delivery platforms and tissue engineering constructs. Strategies to enhance the mechanical and biological performances of chitosan biomaterials are also highlighted.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Review
Pharmacology & Pharmacy
Alice Melocchi, Marco Uboldi, Matteo Cerea, Anastasia Foppoli, Alessandra Maroni, Saliha Moutaharrik, Luca Palugan, Lucia Zema, Andrea Gazzaniga
Summary: Shape memory materials (SMMs) can recover their original shape in response to external stimuli, which could bring significant innovations in the pharmaceutical field. 4D printing, involving SMMs and 3D printing, adds shape evolution possibilities to manufacturing technology.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Article
Chemistry, Multidisciplinary
S. Zu, Z. Wang, S. Zhang, Y. Guo, C. Chen, Q. Zhang, Z. Wang, T. Liu, Q. Liu, Z. Zhang
Summary: In this study, a plant stomata-inspired smart hydrogel capsule was developed using an extrusion-based 4D printing method. The capsule exhibited temperature-responsive drug release behavior and showed great biocompatibility. The bioinspired 4D printed hydrogel capsules are of significant importance in the field of smart controlled drug release.
MATERIALS TODAY CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Andrea Gazzaniga, Anastasia Foppoli, Matteo Cerea, Luca Palugan, Micol Cirilli, Saliha Moutaharrik, Alice Melocchi, Alessandra Maroni
Summary: Four-dimensional printing (4DP) is a new research topic that utilizes smart materials for 3D printing of items that can change their shape over time when exposed to certain external stimuli. The concept of 4D printing involves time as the fourth dimension and has been applied to various fields such as drug delivery and biomedical devices. Two main types of materials, shape memory polymers and shape morphing hydrogels, have been used for 4DP.
INTERNATIONAL JOURNAL OF PHARMACEUTICS-X
(2023)
Review
Biotechnology & Applied Microbiology
Maedeh Rahimnejad, Sepideh Jahangiri, Shahrzad Zirak Hassan Kiadeh, Seyedkamaladdin Rezvaninejad, Zarrin Ahmadi, Sepideh Ahmadi, Moein Safarkhani, Navid Rabiee
Summary: 3D bioprinting is an advanced technology that combines cells and bioactive molecules within a bioscaffold, but it lacks the ability to change or grow in response to a dynamic environment. The emerging field of 4D bioprinting, utilizing smart polymers and hydrogels, adds the dimension of time to 3D bioprinting, allowing for the fabrication of tissue-like structures that can change and reform as tissues are transformed. This has potential applications in biosensing, wound healing, soft robotics, drug delivery, and tissue engineering, but more research is needed to advance this field.
CRITICAL REVIEWS IN BIOTECHNOLOGY
(2023)
Review
Pharmacology & Pharmacy
Sophia N. Economidou, Dennis Douroumis
Summary: This review identified key progress points in using 3D printing to manufacture microneedles over the past 3 years, particularly focusing on advances in photopolymerization and extrusion-based 3D printing. The study highlighted that printing resolution and material properties are the two critical parameters that significantly influence the outcome of microneedle printing endeavors. Finally, the authors attempted to estimate the impact of 3D printing on the transdermal drug delivery market.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Review
Engineering, Biomedical
Moqaddaseh Afzali Naniz, Mohsen Askari, Ali Zolfagharian, Mehrdad Afzali Naniz, Mahdi Bodaghi
Summary: This paper introduces the evolution of natural materials and how the issue of static printed objects not being able to reshape dynamically is addressed through 4D printing technology. It also discusses the recent developments in smart materials and their potential applications in biomedical engineering.
BIOMEDICAL MATERIALS
(2022)
Article
Pharmacology & Pharmacy
Marco Uboldi, Cristiana Perrotta, Claudia Moscheni, Silvia Zecchini, Alessandra Napoli, Chiara Castiglioni, Andrea Gazzaniga, Alice Melocchi, Lucia Zema
Summary: This paper discusses recent advancements in the development of 4D printed drug delivery systems for intravesical administration of drugs. These systems, made of shape-memory pharmaceutical-grade polyvinyl alcohol (PVA), are designed to be inserted into a catheter and re-expand inside the bladder, releasing their content. The prototypes showed potential for controlled release and good recovery of their original shape within 3 minutes.
Article
Biochemistry & Molecular Biology
Rattakorn Boontawee, Ousanee Issarachot, Kanidta Kaewkroek, Ruedeekorn Wiwattanapatapee
Summary: This study successfully developed foldable/expandable films based on natural polymers for stomach-specific delivery and prolonged release of resveratrol. The films exhibited improved solubility, fluid uptake, and resveratrol delivery efficiency. The released polyphenol showed cytotoxic and anti-inflammatory effects.
CURRENT PHARMACEUTICAL BIOTECHNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Samira Malekmohammadi, Negar Sedghi Aminabad, Amin Sabzi, Amir Zarebkohan, Mehdi Razavi, Massoud Vosough, Mahdi Bodaghi, Hajar Maleki
Summary: Smart/stimuli-responsive hydrogels have diverse applications in the biomedical field, with the ability to change behavior in response to external stimuli; technologies like 4D bioprinting have expanded the possibilities of using smart hydrogels in various biomedical applications, driving innovation and development in the field.
Article
Pharmacology & Pharmacy
Luca Palugan, Mattia Spoldi, Francesco Rizzuto, Norberto Guerra, Marco Uboldi, Matteo Cerea, Saliha Moutaharrik, Alice Melocchi, Andrea Gazzaniga, Lucia Zema
Summary: This study evaluated the physico-technological characteristics and performance of commercial cosmetic formulations that are free of E171. A quantitative method based on the CIELab color space was proposed for the first time to study the covering and coloring performance of the coating formulations. The results showed that all the commercially-available E171-free products considered in this study achieved satisfactory covering capability and white color comparable to a standard TiO2-containing reference, without affecting the dissolution performance.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Pharmacology & Pharmacy
Luca Palugan, Saliha Moutaharrik, Micol Cirilli, Andrea Gelain, Alessandra Maroni, Alice Melocchi, Lucia Zema, Anastasia Foppoli, Matteo Cerea
Summary: Dry granulation by roller compaction is a continuous manufacturing technology used in the pharmaceutical industry to improve bulk density and flowability of powder mixtures or prevent segregation issues. Mannitol, a commonly used excipient, can be successfully granulated using roller compaction, resulting in granules with proper size, increased bulk density, and adequate flow properties, which are suitable for tableting.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Luca Palugan, Saliha Moutaharrik, Alessandra Maroni, Anastasia Anna Foppoli, Alice Melocchi, Carlo Vecchio, Andrea Gazzaniga, Matteo Cerea
Summary: A novel punch was proposed for the manufacturing of easy breakable tablets (EBTs) to overcome difficulties in splitting and inconsistent dosing. The study compared the performance of EBTs with traditional breakable tablets (TBTs) using furosemide powder formulation for orally disintegrating tablets (ODTs). The results showed that EBTs manufactured by the novel punch exhibited better splitting behavior and lower mass loss after breaking, indicating the usefulness of the EBT punch in overcoming drawbacks associated with divisible tablets.
Article
Pharmacology & Pharmacy
S. Moutaharrik, A. Maroni, C. Neut, C. Dubuquoy, L. Dubuquoy, A. Foppoli, M. Cerea, L. Palugan, F. Siepmann, J. Siepmann, A. Gazzaniga
Summary: A novel drug delivery system based on multiple drug release triggers was developed and evaluated for oral colon delivery, with a specific focus on inflammatory bowel disease (IBD) therapy. The system demonstrated pulsatile drug release in different release media and faster drug release in simulated colonic fluid with fecal bacteria from IBD patients. Promising results were observed in a preliminary rat study, indicating potential therapeutic effects on colitis progression and microbiota alteration.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Marco Uboldi, Chiara Pasini, Stefano Pandini, Francesco Baldi, Francesco Briatico-Vangosa, Nicoletta Inverardi, Alessandra Maroni, Saliha Moutaharrik, Alice Melocchi, Andrea Gazzaniga, Lucia Zema
Summary: In this study, expandable organ-retentive prototypes were fabricated using hot melt extrusion, and the application of insoluble permeable coatings was evaluated to improve mechanical resistance and slow down drug release. The effectiveness of the proposed strategy was demonstrated by the experimental results.
Review
Pharmacology & Pharmacy
Andrea Gazzaniga, Saliha Moutaharrik, Ilaria Filippin, Anastasia Foppoli, Luca Palugan, Alessandra Maroni, Matteo Cerea
Summary: Despite poor absorption properties, delivery to the colon of bioactive compounds administered by the oral route has become a focus of pharmaceutical research. Time-dependent systems, which rely on relatively constant small intestine transit time, are commonly used for colonic release of drugs.
Article
Pharmacology & Pharmacy
Berta Bosch, Saliha Moutaharrik, Andrea Gazzaniga, Kaisa Hiippala, Helder A. Santos, Alessandra Maroni, Reetta Satokari
Summary: The O. splanchnicus 57 strain was successfully formulated for oral colonic release, showing anti-inflammatory properties, which could be used in the treatment of inflammatory bowel disease.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Andrea Gazzaniga, Anastasia Foppoli, Matteo Cerea, Luca Palugan, Micol Cirilli, Saliha Moutaharrik, Alice Melocchi, Alessandra Maroni
Summary: Four-dimensional printing (4DP) is a new research topic that utilizes smart materials for 3D printing of items that can change their shape over time when exposed to certain external stimuli. The concept of 4D printing involves time as the fourth dimension and has been applied to various fields such as drug delivery and biomedical devices. Two main types of materials, shape memory polymers and shape morphing hydrogels, have been used for 4DP.
INTERNATIONAL JOURNAL OF PHARMACEUTICS-X
(2023)
Article
Instruments & Instrumentation
Saliha Moutaharrik, Gabriele Meroni, Alessio Soggiu, Anastasia Foppoli, Matteo Cerea, Luca Palugan, Francesca Caloni, Piera Anna Martino, Andrea Gazzaniga, Alessandra Maroni
Summary: This study developed a double-coated delivery system that leverages intestinal microbiota, pH, and transit time for reliable colonic release. The system demonstrated feasibility and the ability of guar gum to trigger release in the presence of colon bacteria without impairing the barrier properties of the coating.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2023)
Review
Chemistry, Multidisciplinary
Zhiyuan Shi, Yong Hu, Xin Li
Summary: Controlled drug delivery systems that can respond to mechanical force offer a unique solution for on-demand drug activation and release. Among various mechanical stimuli, ultrasound (US) has advantages in achieving spatiotemporally controlled drug release. Traditional US-triggered drug release relies on heat-induced phase transitions or chemical transformations, while the cutting-edge approach of Sonopharmacology leverages polymer mechanochemistry. The remaining challenges and potential future directions in this field are also discussed.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Lijie Zheng, Yuanzheng Chen, Xun Gu, Yingying Li, Hanqing Zhao, Wenjun Shao, Tao Ma, Chuanbin Wu, Qingqing Wang
Summary: In this study, a novel dosage form consisting of dissolving microneedles and an adhesive transdermal patch was developed for the treatment of rheumatoid arthritis. In vitro and in vivo experiments demonstrated that the combination of drugs delivered by this dosage form effectively reduced joint inflammation and damage.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Kyungjik Yang, Hwa Seung Han, Seung Hwan An, Kyung Hoon Park, Keonwook Nam, Shinha Hwang, Yuyeon Lee, Sung Yeon Cho, Taehyung Kim, Deokyeong Choe, Sang Won Kim, Wonkyu Yu, Hyunah Lee, Jiyong Park, Sangguan You, Dong- Gyu Jo, Ki Young Choi, Young Hoon Roh, Jae Hyung Park
Summary: This study developed CP-loaded CS microcapsules to enhance the oral bioavailability of CP through controlled gastrointestinal delivery. The optimized microcapsules exhibited desirable physicochemical properties, showed anti-photoaging effects via antioxidant activity, and achieved controlled release in the gastrointestinal tract. This research provides a simple and economical approach for enhancing the oral bioavailability of CP for customized bioactive compound administration.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Huiyang Li, Shuo Liu, Wenjin Dai, Bingmei Yao, Yong Zhou, Sujia Si, Hairong Yu, Riguang Zhao, Fang Jin, Liqun Jiang
Summary: Changes in bodily fluid pressures are crucial in diseases like high-altitude pulmonary edema (HAPE). Researchers have developed hydrostatic pressure-sensitive multivesicular liposomes (PSMVLs) that can release drugs in response to pressure changes, with potential applications in HAPE treatment. Animal experiments showed that this system provides better protection for lung tissues and respiratory function, reducing the occurrence of pulmonary edema.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Qian Hu, Hongbing Lan, Yinmei Tian, Xiaonan Li, Mengmeng Wang, Jiao Zhang, Yulin Yu, Wei Chen, Li Kong, Yuanyuan Guo, Zhiping Zhang
Summary: Coacervate droplets formed through liquid-liquid phase separation have potential as delivery vesicles for therapeutics. However, their lack of physiological stability and membranes are challenges. In this study, polylysine-polynucleotide complex coacervate droplets with favorable stability were formulated to concentrate molecules and nanoparticles. Phospholipid membranes were further coated on the droplets to create coacervate-based artificial protocells (ArtPC) with membrane-like structures. These biofunctional ArtPC effectively reduced blood uric acid levels and prevented renal injuries.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Xiaowei Wang, Hongwei Lu, Fang Luo, Dan Wang, Apeng Wang, Xuelei Wang, Wenkai Feng, Xiaobo Wang, Jiayi Su, Mingliang Liu, Guimin Xia
Summary: Four novel lipid-like GEM diesters were synthesized and encapsulated into liposomes to improve the antitumor efficacy of Gemcitabine. The liposomes loaded with dimyristoyl GEM (LipodmGEM) showed enhanced cellular uptake, improved inhibition of cell migration, and a greatly extended half-life compared to free Gemcitabine. LipodmGEM successfully enriched the drug in the tumor and exhibited excellent anticancer efficacy in vivo with negligible systemic toxicity.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Pengyu Li, Jieyi Pan, Yating Dong, Yingying Sun, Yalong Wang, Kang Liao, Yili Chen, Xin Deng, Shihui Yu, Haiyan Hu
Summary: Chronic pulmonary infection caused by Pseudomonas aeruginosa is a serious public health problem with high mortality rates. In this study, infection-microenvironment responsive nanoparticles were developed to eradicate biofilms and inhibit virulence. These nanoparticles showed promising results in treating chronic pulmonary infections.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Yajing Sun, Ze Lu, John A. Taylor, Jessie L. S. Au
Summary: A recent development in cancer chemotherapy is the use of cytotoxics to induce tumor-specific immune response through immunogenic cell death (ICD). This study describes a method that utilizes immunostaining and machine-learning to identify cells with ecto-CRT in intact 3-dimensional tissues. The method was successfully applied to study drug-induced ICD in human bladder cancer.
JOURNAL OF CONTROLLED RELEASE
(2024)
Review
Chemistry, Multidisciplinary
Rafat Ali, Shantanu Sen, Rohil Hameed, Aamir Nazir, Sandeep Verma
Summary: This review provides a focused overview of emerging strategies for delivering gasotransmitters in a controlled and sustained manner to reestablish neurophysiological homeostasis.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Jing Chen, Xinyi Zhang, Jinshen Zhang, Zhaoxia Wang, Guilan Zhu, Ming Geng, Jinmiao Zhu, Yajun Chen, Wei Wang, Youcui Xu
Summary: In this study, a multifunctional responsive hydrogel system was developed for synergistic reoxygenation and chemo/photothermal therapy. The hydrogel system showed both therapeutic effects against metastatic breast cancer and wound infection, making it a promising strategy for treating and preventing tumor recurrence and associated wound infection.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Baoshan Huang, Na Zhang, Xinying Qiu, Rui Zeng, Shuimiao Wang, Mengxia Hua, Qing Li, Kaihui Nan, Sen Lin
Summary: This study revealed that robust ROS can oxidize mitochondrial DNA (ox-mtDNA) and cause its release into the cytosol, resulting in the activation of NLRP3 inflammasome. By using the mitochondria-targeted antioxidant SkQ1 and a novel mitochondria-targeted nanoparticle (SkQ1 NP), it was found that mitochondrial ROS scavenging could in situ inhibit DED-induced mtDNA oxidation and suppress NLRP3-mediated inflammation.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Wenqi Liu, Cheng Hu, Linyu Long, Shuyi He, Wen Zhang, Zhicun Wang, Li Yang, Yunbing Wang
Summary: Myocardial infarction is the leading cause of cardiovascular mortality, and current treatment methods have limitations. This study developed a smart carrier that can release different therapeutic substances for different pathological processes, effectively improving cardiac function, promoting cardiac repair, and preventing ventricular remodeling.
JOURNAL OF CONTROLLED RELEASE
(2024)