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Design and Characterization of Functional, Light-Responsive Materials for Drug Delivery and Tissue Engineering

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 22291

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Special Issue Editors

Dr. Giulia Suarato

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Guest Editor

Smart Materials Group, Translational Pharmacology Facility, Istituto Italiano di Tecnologia, 16163 Genoa, Italy
Interests: smart drug delivery; tissue engineering; naturally-derived polymers; nanoparticles; nano diagnostics; wound healing

Dr. Rossella Castagna

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Guest Editor

1. Nanoprobes and Nanoswitches group, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute for Science and Technology, 08028 Barcelona, Spain
2. Biotechnology group, Latvian Institute of Organic Synthesis (LIOS), LV-1006 Riga, Latvia
Interests: photopharmacology; photoactive compounds; biohybrid materials; electrospinning

Prof. Dr. Giuseppina Sandri

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Guest Editor

Department of Drug Sciences, University of Pavia, viale Taramelli 12, 27100 Pavia, Italy
Interests: nanomaterials; nanoparticles; electrospinning; bioadhesion; in vitro model
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

There has been a continous effort to conceptualize innovative functional drug-delivery systems and cellular support platforms, that are able to overcome classical limitations (e.g., extensive tissue penetration, limited intracellular uptake, uneven and uncomplete degradation), while exerting a distinct therapeutic function. In recent years, smart materials that can be remotely activated or controlled through different light sources (NIR, UV, visible) have gained the interest of both the scientific and clinical communities, thanks to their potential applications in translational nanomedicine. In fact, photo-activable constructs, once internalized by the host organism and spacially localized to the specific site of action, can be stimulated by an external illumination to either release their functional payloads or gradually degrade, without compromising the nearby healthy tissue.

The aim of this Special Issue is to highlight new developments in the field of functional, light-responsive materials, either in the form of photo-activable small molecules or consisting of polymeric chains, hydrogel constructs, electrospun fibers, or micro- and nano-particle assemblies, with light-triggering moieties, as platforms for the effective delivery of drugs and bioactive compounds (e.g., growth factors, nucleic acids, proteins, antioxidants). We welcome original research and review papers dealing with diverse aspects of such smart material designs, from their synthesis and fabrication, to their physico-chemical characterization, and intended applications in pharmaceutical therapeutics and tissue engineering.

Dr. Giulia Suarato
Dr. Rossella Castagna
Dr. Giuseppina Sandri
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

light-triggering
drug delivery
photo-activation
photo-pharmaceutics
degradable scaffolds
tissue reconstruction/tissue engineering
smart polymeric formulations
stimuli-responsive materials

Published Papers (10 papers)

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Research

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15 pages, 4696 KiB

Open AccessArticle

Bioactive Polymeric Nanoparticles of Moringa oleifera Induced Phyto-Photothermal Sensitization for the Enhanced Therapy of Retinoblastoma

by Sushma Venkata Mudigunda, Deepak B. Pemmaraju, Sri Amruthaa Sankaranarayanan and Aravind Kumar Rengan

Pharmaceutics 2023, 15(2), 475; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics15020475 - 31 Jan 2023

Cited by 4 | Viewed by 1970

Abstract

Treatment of retinoblastoma is limited due to its delayed detection and inaccesbility of drugs to reach the retina crossing the blood-retinal barrier. With the advancements in nanotechnology, photothermal therapy (PTT) employing plasmonic nanomaterials and/or NIR dyes have emerged as an affordable alternative owing to the spatial control that is offered by the modality leading to localized and enhanced therapeutic efficacy with minimal invasiveness. However, the modality is limited in its clinical application owing to the increased heat shock resistance of the tumor cells in response to the heat that is generated via PTT. Hence, in this study, we explore the role of novel biomolecular fraction of Moringa oleifera (DFM) encapsulated within a polymeric nanosystem, for its anti-heat shock protein (HSP) activity. The MO extract was co-encapsulated with NIR sensitizing dye, IR820 into a biodegradable polycaprolactone (PCL) nano-delivery system (PMIR NPs). The photothermal transduction efficacy of PMIR NPs was validated in vitro against retinoblastoma cell lines. The inherent fluorescence of DFM was utilized to evaluate the cellular internalization of the PMIR NPs using fluorescence microscopy and flow cytometry. The overall oxidative protein damage and downregulation of HSP70 expression upon treatment with PMIR NPs and NIR laser irradiation was evaluated using densiometric protein analysis and Western blotting. Overall, the PMIR NPs exhibited excellent anti-cancer activity when combined with PTT with downregulated HSP70 expression against retinoblastoma cells. Full article

(This article belongs to the Special Issue Design and Characterization of Functional, Light-Responsive Materials for Drug Delivery and Tissue Engineering)

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19 pages, 3589 KiB

Open AccessArticle

Photothermal Properties of IR-780-Based Nanoparticles Depend on Nanocarrier Design: A Comparative Study on Synthetic Liposomes and Cell Membrane and Hybrid Biomimetic Vesicles

by Júlia Muniz Barcelos, Tácio Gonçalves Hayasaki, Ricardo Costa de Santana, Eliana Martins Lima, Sebastião Antonio Mendanha and Andris Figueiroa Bakuzis

Pharmaceutics 2023, 15(2), 444; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics15020444 - 29 Jan 2023

Cited by 5 | Viewed by 1892

Abstract

Biomimetic nanoparticles hold great promise for photonic-mediated nanomedicine due to the association of the biological functionality of the membrane with the physical/chemical goals of organic/inorganic structures, but studies involving fluorescent biomimetic vesicles are still scarce. The purpose of this article is to determine how photothermal therapy (PTT) with theranostic IR-780-based nanoparticles depends on the dye content, cholesterol content, lipid bilayer phase and cell membrane type. The photophysical responses of synthetic liposomes, cell membrane vesicles and hybrid nanoparticles are compared. The samples were characterized by nanoparticle tracking analysis, photoluminescence, electron spin resonance, and photothermal- and heat-mediated drug release experiments, among other techniques. The photothermal conversion efficiency (PCE) was determined using Roper’s method. All samples excited at 804 nm showed three fluorescence bands, two of them independent of the IR-780 content. Samples with a fluorescence band at around 850 nm showed photobleaching (PBL). Quenching was higher in cell membrane vesicles, while cholesterol inhibited quenching in synthetic liposomes with low dye content. PTT depended on the cell membrane and was more efficient for melanoma than erythrocyte vesicles. Synthetic liposomes containing cholesterol and a high amount of IR-780 presented superior performance in PTT experiments, with a 2.4-fold PCE increase in comparison with free IR-780, no PBL and the ability to heat-trigger doxorubicin release. Full article

(This article belongs to the Special Issue Design and Characterization of Functional, Light-Responsive Materials for Drug Delivery and Tissue Engineering)

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17 pages, 2855 KiB

Open AccessArticle

Anti-Glioma Activity Achieved by Dual Blood–Brain Barrier/Glioma Targeting Naive Chimeric Peptides-Based Co-Assembled Nanophototheranostics

by Taru Dube and Jiban Jyoti Panda

Pharmaceutics 2023, 15(1), 265; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics15010265 - 12 Jan 2023

Cited by 1 | Viewed by 1636

Abstract

Peptide monomers can either self-assemble with themselves enacting a solo-component assembly or they can co-assemble by interacting with other suitable partners to mediate peptide co-assembly. Peptide co-assemblies represent an innovative class of naive, multifunctional, bio-inspired supramolecular constructs that result in the production of nanostructures with widespread functional, structural, and chemical multiplicity. Herein, the co-assembly of novel chimeric peptides (conjugates of T7 (HAIYPRH)/t-Lyp-1 (CGNKRTR) peptides and aurein 1.2 (GLFDIIKKIAESF)) has been explored as a means to produce glioma theranostics exhibiting combinatorial chemo-phototherapy. Briefly, we have reported here the design and solid phase synthesis of a naive generation of twin-functional peptide drugs incorporating the blood–brain barrier (BBB) and glioma dual-targeting functionalities along with anti-glioma activity (G-Anti G and B-Anti G). Additionally, we have addressed their multicomponent co-assembly and explored their potential application as glioma drug delivery vehicles. Our naive peptide drug-based nanoparticles (NPs) successfully demonstrated a heightened glioma-specific delivery and anti-glioma activity. Multicomponent indocyanine green (ICG)-loaded peptide co-assembled NPs (PINPs: with a hydrodynamic size of 348 nm and a zeta-potential of 5 mV) showed enhanced anti-glioma responses in several cellular assays involving C6 cells. These included a mass demolition with no wound closure (i.e., a 100% cell destruction) and around 63% collaborative chemo-phototoxicity (with both a photothermal and photodynamic effect) after near infrared (NIR) 808 laser irradiation. The dual targeting ability of peptide bioconjugates towards both the BBB and glioma cells, presents new opportunities for designing tailored and better peptide-based nanostructures or nanophototheranostics for glioma. Full article

(This article belongs to the Special Issue Design and Characterization of Functional, Light-Responsive Materials for Drug Delivery and Tissue Engineering)

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21 pages, 7145 KiB

Open AccessArticle

Photo-Phytotherapeutic Gel Composed of Copaifera reticulata, Chlorophylls, and k-Carrageenan: A New Perspective for Topical Healing

by Katieli da Silva Souza Campanholi, Ranulfo Combuca da Silva Junior, Renato Sonchini Gonçalves, Mariana Carla de Oliveira, Magali Soares dos Santos Pozza, Angela Tiago Leite, Leandro Herculano da Silva, Luis Carlos Malacarne, Marcos Luciano Bruschi, Leandro Dalcin Castilha, Tatiana Carlesso dos Santos and Wilker Caetano

Pharmaceutics 2022, 14(12), 2580; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14122580 - 24 Nov 2022

Cited by 3 | Viewed by 1546

Abstract

Chronic wound healing represents an impactful financial burden on healthcare systems. In this context, the use of natural products as an alternative therapy reduces costs and maintains effectiveness. Phytotherapeutic gels applied in photodynamic therapy (PDT) have been developed to act as topical healing medicines and antibiotics. The bioactive system is composed of Spirulina sp. (source of chlorophylls) and Copaifera reticulata oil microdroplets, both incorporated into a polymeric blend constituted by kappa-carrageenan (k-car) and F127 copolymer, constituting a system in which all components are bioactive agents. The flow behavior and viscoelasticity of the formulations were investigated. The photodynamic activity was accessed from studies of the inactivation of Staphylococcus aureus bacteria, the main pathogen of hospital relevance. Furthermore, in vivo studies were conducted using eighteen rabbits with dermatitis (grade III and IV) in both paws. The gels showed significant antibiotic potential in vitro, eliminating up to 100% of S. aureus colonies in the presence or absence of light. The k-car reduced 41% of the viable cells; however, its benefits were enhanced by adding chlorophyll and copaiba oil. The animals treated with the phytotherapeutic medicine showed a reduction in lesion size, with healing and re-epithelialization verified in the histological analyses. The animals submitted to PDT displayed noticeable improvement, indicating this therapy’s viability for ulcerative and infected wounds. This behavior was not observed in the iodine control treatment, which worsened the animals’ condition. Therefore, gel formulations were a viable alternative for future pharmaceutical applications, aiming at topical healing. Full article

(This article belongs to the Special Issue Design and Characterization of Functional, Light-Responsive Materials for Drug Delivery and Tissue Engineering)

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18 pages, 4214 KiB

Open AccessArticle

Neuropeptide-Functionalized Gold Nanorod Enhanced Cellular Uptake and Improved In Vitro Photothermal Killing in LRP1-Positive Glioma Cells

by Siva Sankari Sivasoorian, Ritesh Urade, Chien-Chih Chiu and Li-Fang Wang

Pharmaceutics 2022, 14(9), 1939; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14091939 - 13 Sep 2022

Cited by 2 | Viewed by 1758

Abstract

The therapeutic modalities for glioblastoma multiforme fail badly due to the limitations of poor penetration through the blood–brain barrier and the lack of tumor targeting. In this study, we synthesized a neuropeptide (ANGIOPEP-2)-functionalized gold nanorod (GNR-ANGI-2) and systemically evaluated the cellular uptake and photothermal effects enhanced by the neuropeptide functionalization of the gold nanorod under laser or sham exposure. The expression of LRP1, the specific ligand for ANGIOPEP-2, was the highest in C6 cells among five studied glioma cell lines. The cellular internalization studies showed higher uptake of gold nanorods functionalized with ANGIOPEP-2 than of those functionalized with scrambled ANGIOPEP-2. The in vitro photothermal studies of C6 cells treated with GNR-ANGI-2 and laser showed a higher rate of apoptosis at early and late stages than cells treated with GNR-ANGI-2 without laser. Correspondingly, in vitro ROS evaluation showed a higher intensity of ROS production in cells treated with GNR-ANGI-2 under laser irradiation. The Western blotting results indicated that GNR-ANGI-2 with laser exposure activated the caspase pathway of apoptosis, and GNR-ANGI-2 with sham exposure induced autophagy in C6 cells. The current study provides in-depth knowledge on the effective time point for maximum cellular uptake of GNR-ANGI-2 to achieve a better anti-glioma effect. Moreover, by exploring the molecular mechanism of cell death with GNR-ANGI-2-mediated photothermal therapy, we could modify the nanoshuttle with multimodal targets to achieve more efficient anti-glioma therapy in the future. Full article

(This article belongs to the Special Issue Design and Characterization of Functional, Light-Responsive Materials for Drug Delivery and Tissue Engineering)

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11 pages, 1796 KiB

Open AccessArticle

Self-Organization Dynamics of Collagen-like Peptides Crosslinking Is Driven by Rose-Bengal-Mediated Electrostatic Bridges

by Roberto Rosales-Rojas, Matías Zuñiga-Bustos, Francisca Salas-Sepúlveda, Constanza Galaz-Araya, Ricardo A. Zamora and Horacio Poblete

Pharmaceutics 2022, 14(6), 1148; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14061148 - 27 May 2022

Cited by 1 | Viewed by 1569

Abstract

The present work focuses on the computational study of the structural micro-organization of hydrogels based on collagen-like peptides (CLPs) in complex with Rose Bengal (RB). In previous studies, these hydrogels computationally and experimentally demonstrated that when RB was activated by green light, it could generate forms of stable crosslinked structures capable of regenerating biological tissues such as the skin and cornea. Here, we focus on the structural and atomic interactions of two collagen-like peptides (collagen-like peptide I (CLPI), and collagen-like peptide II, (CLPII)) in the presence and absence of RB, highlighting the acquired three-dimensional organization and going deep into the stabilization effect caused by the dye. Our results suggest that the dye could generate a ternary ground-state complex between collagen-like peptide fibers, specifically with positively charged amino acids (Lys in CLPI and Arg in CLPII), thus stabilizing ordered three-dimensional structures. The discoveries generated in this study provide the structural and atomic bases for the subsequent rational development of new synthetic peptides with improved characteristics for applications in the regeneration of biological tissues during photochemical tissue bonding therapies. Full article

(This article belongs to the Special Issue Design and Characterization of Functional, Light-Responsive Materials for Drug Delivery and Tissue Engineering)

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13 pages, 27347 KiB

Open AccessArticle

Controlling Antimicrobial Activity of Quinolones Using Visible/NIR Light-Activated BODIPY Photocages

by Elena Contreras-García, Carmen Lozano, Cristina García-Iriepa, Marco Marazzi, Arthur H. Winter, Carmen Torres and Diego Sampedro

Pharmaceutics 2022, 14(5), 1070; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14051070 - 17 May 2022

Cited by 12 | Viewed by 2545

Abstract

Controlling the activity of a pharmaceutical agent using light offers improved selectivity, reduction of adverse effects, and decreased environmental build-up. These benefits are especially attractive for antibiotics. Herein, we report a series of photoreleasable quinolones, which can be activated using visible/NIR light (520–800 nm). We have used BODIPY photocages with strong absorption in the visible to protect two different quinolone-based compounds and deactivate their antimicrobial properties. This activity could be recovered upon green or red light irradiation. A comprehensive computational study provides new insight into the reaction mechanism, revealing the relevance of considering explicit solvent molecules. The triplet excited state is populated and the photodissociation is assisted by the solvent. The light-controlled activity of these compounds has been assessed on a quinolone-susceptible E. coli strain. Up to a 32-fold change in the antimicrobial activity was measured. Full article

(This article belongs to the Special Issue Design and Characterization of Functional, Light-Responsive Materials for Drug Delivery and Tissue Engineering)

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Review

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38 pages, 3331 KiB

Open AccessEditor’s ChoiceReview

Light-Based Anti-Biofilm and Antibacterial Strategies

by Ambreen Kauser, Emilio Parisini, Giulia Suarato and Rossella Castagna

Pharmaceutics 2023, 15(8), 2106; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics15082106 - 09 Aug 2023

Cited by 4 | Viewed by 2203

Abstract

Biofilm formation and antimicrobial resistance pose significant challenges not only in clinical settings (i.e., implant-associated infections, endocarditis, and urinary tract infections) but also in industrial settings and in the environment, where the spreading of antibiotic-resistant bacteria is on the rise. Indeed, developing effective strategies to prevent biofilm formation and treat infections will be one of the major global challenges in the next few years. As traditional pharmacological treatments are becoming inadequate to curb this problem, a constant commitment to the exploration of novel therapeutic strategies is necessary. Light-triggered therapies have emerged as promising alternatives to traditional approaches due to their non-invasive nature, precise spatial and temporal control, and potential multifunctional properties. Here, we provide a comprehensive overview of the different biofilm formation stages and the molecular mechanism of biofilm disruption, with a major focus on the quorum sensing machinery. Moreover, we highlight the principal guidelines for the development of light-responsive materials and photosensitive compounds. The synergistic effects of combining light-triggered therapies with conventional treatments are also discussed. Through elegant molecular and material design solutions, remarkable results have been achieved in the fight against biofilm formation and antibacterial resistance. However, further research and development in this field are essential to optimize therapeutic strategies and translate them into clinical and industrial applications, ultimately addressing the global challenges posed by biofilm and antimicrobial resistance. Full article

(This article belongs to the Special Issue Design and Characterization of Functional, Light-Responsive Materials for Drug Delivery and Tissue Engineering)

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21 pages, 4032 KiB

Open AccessReview

Curcumin a Natural Phenol and Its Therapeutic Role in Cancer and Photodynamic Therapy: A Review

by Glory Kah, Rahul Chandran and Heidi Abrahamse

Pharmaceutics 2023, 15(2), 639; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics15020639 - 14 Feb 2023

Cited by 19 | Viewed by 3403

Abstract

Cancer continues to cause an alarming number of deaths globally, and its burden on the health system is significant. Though different conventional therapeutic procedures are exploited for cancer treatment, the prevalence and death rates remain elevated. These, therefore, insinuate that novel and more efficient treatment procedures are needed for cancer. Curcumin, a bioactive, natural, phenolic compound isolated from the rhizome of the herbaceous plant turmeric, is receiving great interest for its exciting and broad pharmacological properties. Curcumin presents anticancer therapeutic capacities and can be utilized as a photosensitizing drug in cancer photodynamic therapy (PDT). Nonetheless, curcumin′s poor bioavailability and related pharmacokinetics limit its clinical utility in cancer treatment. This review looks at the physical and chemical properties, bioavailability, and safety of curcumin, while focusing on curcumin as an agent in cancer therapy and as a photosensitizer in cancer PDT. The possible mechanisms and cellular targets of curcumin in cancer therapy and PDT are highlighted. Furthermore, recent improvements in curcumin’s bioavailability in cancer therapy using nanoformulations and delivery systems are presented. Full article

(This article belongs to the Special Issue Design and Characterization of Functional, Light-Responsive Materials for Drug Delivery and Tissue Engineering)

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22 pages, 1824 KiB

Open AccessReview

Multifunctional Photoactive Nanomaterials for Photodynamic Therapy against Tumor: Recent Advancements and Perspectives

by Rupesh Jain, Shambo Mohanty, Ila Sarode, Swati Biswas, Gautam Singhvi and Sunil Kumar Dubey

Pharmaceutics 2023, 15(1), 109; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics15010109 - 28 Dec 2022

Cited by 8 | Viewed by 1853

Abstract

Numerous treatments are available for cancer, including chemotherapy, immunotherapy, radiation therapy, hormone therapy, biomarker testing, surgery, photodynamic therapy, etc. Photodynamic therapy (PDT) is an effective, non-invasive, novel, and clinically approved strategy to treat cancer. In PDT, three main agents are utilized, i.e., photosensitizer (PS) drug, oxygen, and light. At first, the photosensitizer is injected into blood circulation or applied topically, where it quickly becomes absorbed or accumulated at the tumor site passively or actively. Afterward, the tumor is irradiated with light which leads to the activation of the photosensitizing molecule. PS produces the reactive oxygen species (ROS), resulting in the death of the tumor cell. However, the effectiveness of PDT for tumor destruction is mainly dependent on the cellular uptake and water solubility of photosensitizer molecules. Therefore, the delivery of photosensitizer molecules to the tumor cell is essential in PDT against cancer. The non-specific distribution of photosensitizer results in unwanted side effects and unsuccessful therapeutic outcomes. Therefore, to improve PDT clinical outcomes, the current research is mostly focused on developing actively targeted photosensitizer molecules, which provide a high cellular uptake and high absorption capacity to the tumor site by overcoming the problem associated with conventional PDT. Therefore, this review aims to provide current knowledge on various types of actively and passively targeted organic and inorganic nanocarriers for different cancers. Full article

(This article belongs to the Special Issue Design and Characterization of Functional, Light-Responsive Materials for Drug Delivery and Tissue Engineering)

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