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24 pages, 3155 KiB

Open AccessArticle

coupled Hydrodynamic Flow Focusing (cHFF) to Engineer Lipid–Polymer Nanoparticles (LiPoNs) for Multimodal Imaging and Theranostic Applications

by Felicia Roffo, Alfonso Maria Ponsiglione, Paolo Antonio Netti and Enza Torino

Biomedicines 2022, 10(2), 438; https://doi.org/10.3390/biomedicines10020438 - 14 Feb 2022

Cited by 8 | Viewed by 2906

Abstract

An optimal design of nanocarriers is required to overcome the gap between synthetic and biological identity, improving the clinical translation of nanomedicine. A new generation of hybrid vehicles based on lipid–polymer coupling, obtained by Microfluidics, is proposed and validated for theranostics and multimodal [...] Read more.

An optimal design of nanocarriers is required to overcome the gap between synthetic and biological identity, improving the clinical translation of nanomedicine. A new generation of hybrid vehicles based on lipid–polymer coupling, obtained by Microfluidics, is proposed and validated for theranostics and multimodal imaging applications. A coupled Hydrodynamic Flow Focusing (cHFF) is exploited to control the time scales of solvent exchange and the coupling of the polymer nanoprecipitation with the lipid self-assembly simultaneously, guiding the formation of Lipid–Polymer NPs (LiPoNs). This hybrid lipid–polymeric tool is made up of core–shell structure, where a polymeric chitosan core is enveloped in a lipid bilayer, capable of co-encapsulating simultaneously Gd-DTPA and Irinotecan/Atto 633 compounds. As a result, a monodisperse population of hybrid NPs with an average size of 77 nm, with preserved structural integrity in different environmental conditions and high biocompatibility, can be used for MRI and Optical applications. Furthermore, preliminary results show the enhanced delivery and therapeutic efficacy of Irinotecan-loaded hybrid formulation against U87 MG cancers cells. Full article

(This article belongs to the Special Issue Theranostic Drug Delivery: Prospects and Problems)

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13 pages, 1961 KiB

Open AccessArticle

Transdermal Delivery of Lidocaine-Loaded Elastic Nano-Liposomes with Microneedle Array Pretreatment

by Yang Liu, Maosen Cheng, Junqi Zhao, Xiaoying Zhang, Zhen Huang, Yuhui Zang, Ying Ding, Junfeng Zhang and Zhi Ding

Biomedicines 2021, 9(6), 592; https://doi.org/10.3390/biomedicines9060592 - 23 May 2021

Cited by 17 | Viewed by 3491

Abstract

This study aimed to improve the transdermal delivery of lidocaine hydrochloride (LidH) using elastic nano-liposomes (ENLs) and microneedle (MN) array pretreatment. LidH-containing ENLs were prepared using soybean phosphatidylcholine and cholesterol, with Span 80 or Tween 80, using a reverse-phase evaporation method. The ENL [...] Read more.

This study aimed to improve the transdermal delivery of lidocaine hydrochloride (LidH) using elastic nano-liposomes (ENLs) and microneedle (MN) array pretreatment. LidH-containing ENLs were prepared using soybean phosphatidylcholine and cholesterol, with Span 80 or Tween 80, using a reverse-phase evaporation method. The ENL particle size, stability, and encapsulation efficiency (EE) were characterized and optimized based on the component ratio, pH, and type of surfactant used. In vitro transdermal diffusion study was performed on MN-pretreated mouse skin using Franz diffusion cells. The anesthetic effects of LidH in various formulations after dermal application were evaluated in vivo in rats by measuring the tail withdrawal latency after photothermic stimulation. Stable LidH-loaded Tween 80 or Span 80 ENLs were obtained with particle sizes of 115.8 and 146.6 nm and EEs of 27% and 20%, respectively. The formulations did not exert any cytotoxicity in HaCaT cells. Tween 80 and Span 80 ENL formulations showed enhanced LidH delivery on pretreated mice skin in vitro and prolonged the anesthetic effect in vivo compared to that by LidH application alone. LidH-loaded ENLs applied to MN-pretreated skin can shorten the onset time and prolong the anesthetic effect safely, which merits their further optimization and practical application. Full article

(This article belongs to the Special Issue Theranostic Drug Delivery: Prospects and Problems)

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20 pages, 6192 KiB

Open AccessArticle

Multi-Smart and Scalable Bioligands-Free Nanomedical Platform for Intratumorally Targeted Tambjamine Delivery, a Difficult to Administrate Highly Cytotoxic Drug

by Marta Pérez-Hernández, Cristina Cuscó, Cristina Benítez-García, Joaquin Bonelli, Marina Nuevo-Fonoll, Aroa Soriano, David Martínez-García, Alain Arias-Betancur, María García-Valverde, Miguel F. Segura, Roberto Quesada, Josep Rocas, Vanessa Soto-Cerrato and Ricardo Pérez-Tomás

Biomedicines 2021, 9(5), 508; https://doi.org/10.3390/biomedicines9050508 - 04 May 2021

Cited by 6 | Viewed by 2744

Abstract

Cancer is one of the leading causes of mortality worldwide due, in part, to limited success of some current therapeutic approaches. The clinical potential of many promising drugs is restricted by their systemic toxicity and lack of selectivity towards cancer cells, leading to [...] Read more.

Cancer is one of the leading causes of mortality worldwide due, in part, to limited success of some current therapeutic approaches. The clinical potential of many promising drugs is restricted by their systemic toxicity and lack of selectivity towards cancer cells, leading to insufficient drug concentration at the tumor site. To overcome these hurdles, we developed a novel drug delivery system based on polyurea/polyurethane nanocapsules (NCs) showing pH-synchronized amphoteric properties that facilitate their accumulation and selectivity into acidic tissues, such as tumor microenvironment. We have demonstrated that the anticancer drug used in this study, a hydrophobic anionophore named T21, increases its cytotoxic activity in acidic conditions when nanoencapsulated, which correlates with a more efficient cellular internalization. A biodistribution assay performed in mice has shown that the NCs are able to reach the tumor and the observed systemic toxicity of the free drug is significantly reduced in vivo when nanoencapsulated. Additionally, T21 antitumor activity is preserved, accompanied by tumor mass reduction compared to control mice. Altogether, this work shows these NCs as a potential drug delivery system able to reach the tumor microenvironment, reducing the undesired systemic toxic effects. Moreover, these nanosystems are prepared under scalable methodologies and straightforward process, and provide tumor selectivity through a smart mechanism independent of targeting ligands. Full article

(This article belongs to the Special Issue Theranostic Drug Delivery: Prospects and Problems)

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15 pages, 2049 KiB

Open AccessArticle

Rational Design of Albumin Theranostic Conjugates for Gold Nanoparticles Anticancer Drugs: Where the Seed Meets the Soil?

by Tatyana V. Popova, Inna A. Pyshnaya, Olga D. Zakharova, Andrey E. Akulov, Oleg B. Shevelev, Julia Poletaeva, Evgenii L. Zavjalov, Vladimir N. Silnikov, Elena I. Ryabchikova and Tatyana S. Godovikova

Biomedicines 2021, 9(1), 74; https://doi.org/10.3390/biomedicines9010074 - 13 Jan 2021

Cited by 12 | Viewed by 3118

Abstract

Multifunctional gold nanoparticles (AuNPs) may serve as a scaffold to integrate diagnostic and therapeutic functions into one theranostic system, thereby simultaneously facilitating diagnosis and therapy and monitoring therapeutic responses. Herein, albumin-AuNP theranostic agents have been obtained by conjugation of an anticancer nucleotide trifluorothymidine [...] Read more.

Multifunctional gold nanoparticles (AuNPs) may serve as a scaffold to integrate diagnostic and therapeutic functions into one theranostic system, thereby simultaneously facilitating diagnosis and therapy and monitoring therapeutic responses. Herein, albumin-AuNP theranostic agents have been obtained by conjugation of an anticancer nucleotide trifluorothymidine (TFT) or a boron-neutron capture therapy drug undecahydro-closo-dodecaborate (B₁₂H₁₂) to bimodal human serum albumin (HSA) followed by reacting of the albumin conjugates with AuNPs. In vitro studies have revealed a stronger cytotoxicity by the AuNPs decorated with the TFT-tagged bimodal HSA than by the boronated albumin conjugates. Despite long circulation time, lack of the significant accumulation in the tumor was observed for the AuNP theranostic conjugates. Our unique labelling strategy allows for monitoring of spatial distribution of the AuNPs theranostic in vivo in real time with high sensitivity, thus reducing the number of animals required for testing and optimizing new nanosystems as chemotherapeutic agents and boron-neutron capture therapy drug candidates. Full article

(This article belongs to the Special Issue Theranostic Drug Delivery: Prospects and Problems)

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Review

Jump to: Research

20 pages, 677 KiB

Open AccessReview

Molecular Perspective of Nanoparticle Mediated Therapeutic Targeting in Breast Cancer: An Odyssey of Endoplasmic Reticulum Unfolded Protein Response (UPR^ER) and Beyond

by Safikur Rahman, Vijay Kumar, Anuj Kumar, Tasduq S. Abdullah, Irfan A. Rather and Arif Tasleem Jan

Biomedicines 2021, 9(6), 635; https://doi.org/10.3390/biomedicines9060635 - 02 Jun 2021

Cited by 8 | Viewed by 3337

Abstract

Breast cancer (BC) is the second most frequent cause of death among women. Representing a complex and heterogeneous type of cancer, its occurrence is attributed by both genetic (gene mutations, e.g., BRCA1, BRCA2) and non-genetic (race, ethnicity, etc.) risk factors. The effectiveness of [...] Read more.

Breast cancer (BC) is the second most frequent cause of death among women. Representing a complex and heterogeneous type of cancer, its occurrence is attributed by both genetic (gene mutations, e.g., BRCA1, BRCA2) and non-genetic (race, ethnicity, etc.) risk factors. The effectiveness of available treatment regimens (small molecules, cytotoxic agents, and inhibitors) decreased due to their poor penetration across biological barriers, limited targeting, and rapid body clearance along with their effect on normal resident cells of bone marrow, gastrointestinal tract, and hair follicles. This significantly reduced their clinical outcomes, which led to an unprecedented increase in the number of cases worldwide. Nanomedicine, a nano-formulation of therapeutics, emerged as a versatile delivering module for employment in achieving the effective and target specific delivery of pharmaceutical payloads. Adoption of nanotechnological approaches in delivering therapeutic molecules to target cells ensures not only reduced immune response and toxicity, but increases the stability of therapeutic entities in the systemic circulation that averts their degradation and as such increased extravasations and accumulation via enhanced permeation and the retention (EPR) effect in target tissues. Additionally, nanoparticle (NP)-induced ER stress, which enhances apoptosis and autophagy, has been utilized as a combative strategy in the treatment of cancerous cells. As nanoparticles-based avenues have been capitalized to achieve better efficacy of the new genera of therapeutics with enhanced specificity and safety, the present study is aimed at providing the fundamentals of BC, nanotechnological modules (organic, inorganic, and hybrid) employed in delivering different therapeutic molecules, and mechanistic insights of nano-ER stress induced apoptosis and autophagy with a perspective of exploring this avenue for use in the nano-toxicological studies. Furthermore, the current scenario of USA FDA approved nano-formulations and the future perspective of nanotechnological based interventions to overcome the existing challenges are also discussed. Full article

(This article belongs to the Special Issue Theranostic Drug Delivery: Prospects and Problems)

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20 pages, 2226 KiB

Open AccessReview

Methodical Design of Viral Vaccines Based on Avant-Garde Nanocarriers: A Multi-Domain Narrative Review

by Ehsan Raoufi, Bahar Bahramimeimandi, M. Salehi-Shadkami, Patcharida Chaosri and M. R. Mozafari

Biomedicines 2021, 9(5), 520; https://doi.org/10.3390/biomedicines9050520 - 06 May 2021

Cited by 16 | Viewed by 4425

Abstract

The current health crisis caused by coronavirus 2019 (COVID-19) and associated pathogens emphasize the urgent need for vaccine systems that can generate protective and long-lasting immune responses. Vaccination, employing peptides, nucleic acids, and other molecules, or using pathogen-based strategies, in fact, is one [...] Read more.

The current health crisis caused by coronavirus 2019 (COVID-19) and associated pathogens emphasize the urgent need for vaccine systems that can generate protective and long-lasting immune responses. Vaccination, employing peptides, nucleic acids, and other molecules, or using pathogen-based strategies, in fact, is one of the most potent approaches in the management of viral diseases. However, the vaccine candidate requires protection from degradation and precise delivery to the target cells. This can be achieved by employing different types of drug and vaccine delivery strategies, among which, nanotechnology-based systems seem to be more promising. This entry aims to provide insight into major aspects of vaccine design and formulation to address different diseases, including the recent outbreak of SARS-CoV-2. Special emphasis of this review is on the technical and practical aspects of vaccine construction and theranostic approaches to precisely target and localize the active compounds. Full article

(This article belongs to the Special Issue Theranostic Drug Delivery: Prospects and Problems)

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22 pages, 5155 KiB

Open AccessReview

Controlling Antibiotic Release from Polymethylmethacrylate Bone Cement

by Victoria Wall, Thi-Hiep Nguyen, Nghi Nguyen and Phong A. Tran

Biomedicines 2021, 9(1), 26; https://doi.org/10.3390/biomedicines9010026 - 01 Jan 2021

Cited by 33 | Viewed by 5583

Abstract

Bone cement is used as a mortar for securing bone implants, as bone void fillers or as spacers in orthopaedic surgery. Antibiotic-loaded bone cements (ALBCs) have been used to prevent and treat prosthetic joint infections by providing a high antibiotic concentration around the [...] Read more.

Bone cement is used as a mortar for securing bone implants, as bone void fillers or as spacers in orthopaedic surgery. Antibiotic-loaded bone cements (ALBCs) have been used to prevent and treat prosthetic joint infections by providing a high antibiotic concentration around the implanted prosthesis. High antibiotic concentrations are, on the other hand, often associated with tissue toxicity. Controlling antibiotic release from ALBCS is key to achieving effective infection control and promoting prosthesis integration with the surrounding bone tissue. However, current ALBCs still need significant improvement in regulating antibiotic release. In this review, we first provide a brief introduction to prosthetic joint infections, and the background concepts of therapeutic efficacy and toxicity in antibiotics. We then review the current state of ALBCs and their release characteristics before focusing on the research and development in controlling the antibiotic release and osteo-conductivity/inductivity. We then conclude by a discussion on the need for better in vitro experiment designs such that the release results can be extrapolated to predict better the local antibiotic concentrations in vivo. Full article

(This article belongs to the Special Issue Theranostic Drug Delivery: Prospects and Problems)

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16 pages, 1803 KiB

Open AccessReview

Lectin Protein as a Promising Component to Functionalize Micelles, Liposomes and Lipid NPs against Coronavirus

by Mehran Alavi, Kofi Asare-Addo and Ali Nokhodchi

Biomedicines 2020, 8(12), 580; https://doi.org/10.3390/biomedicines8120580 - 07 Dec 2020

Cited by 23 | Viewed by 5417

Abstract

The outbreak of a novel strain coronavirus as the causative agent of COVID-19 pneumonia, first identified in Wuhan, China in December 2019, has resulted in considerable focus on virulence abilities of coronavirus. Lectins are natural proteins with the ability to bind specific carbohydrates [...] Read more.

The outbreak of a novel strain coronavirus as the causative agent of COVID-19 pneumonia, first identified in Wuhan, China in December 2019, has resulted in considerable focus on virulence abilities of coronavirus. Lectins are natural proteins with the ability to bind specific carbohydrates related to various microorganisms, including viruses, bacteria, fungi and parasites. Lectins have the ability to agglutinate and neutralize these pathogeneses. The delivery of the encapsulated antiviral agents or vaccines across the cell membrane can be possible by functionalized micellar and liposomal formulations. In this mini-review, recent advances and challenges related to important lectins with inhibition activities against coronaviruses are presented to obtain a novel viewpoint of microformulations or nanoformulations by micellar and liposomal cell-binding carriers. Full article

(This article belongs to the Special Issue Theranostic Drug Delivery: Prospects and Problems)

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