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Pharmaceutics
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Nanotechnology-Based Drug Formulations and Drug Delivery Systems
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Nanotechnology-Based Drug Formulations and Drug Delivery Systems

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (20 July 2023) | Viewed by 14229

Special Issue Editor

Dr. Manu Lopus

E-Mail Website
Guest Editor
School of Biological Sciences, UM-DAE Centre for Excellence in Basic Sciences, Mumbai 400098, India
Interests: cancer therapeutics; nanomedicine; chemical biology; cell cycle

Special Issue Information

Dear Colleagues,

Thousands of drugs have been approved by different government agencies for the treatment of a variety of illnesses. However, when it comes to treating complicated diseases such as cancer, many drugs used in the clinic often fall below the necessary expectations. Several factors can account for this: evolving drug resistance mechanisms, dose-limiting and often patient-specific side effects, and lack of target specificity can all hamper or nullify their efficacy. With advanced, computer-assisted rational drug design strategies and smart drug repurposing approaches, some improvements have been made, and promising directions are now opening up. However, the effective and safe delivery of drugs remains a persistent challenge in cancer therapy. With the advent of modern nanotechnology, researchers in the field of cancer therapeutic research are exploring several revolutionary approaches. By enabling investigators to create size-, shape- and surface-chemistry-optimized nanoformulations, it is now possible to precisely target cells and proteins of interest, reduce off-target toxicity, and ensure the enhanced, target-specific delivery of drug molecules.

Nanocarriers (NCs) are potential vehicles designed to safely carry drug molecules to the site of interest. NCs can be broadly categorized into three groups: organic, inorganic and virus-based. Organic nanocarriers include solid lipid nanoparticles (SLNs), liposomes, niosomes, dendrimers, polymeric nanoparticles, and polymeric micelles. Prominent among inorganic nanocarriers are carbon nanotubes and mesoporous silica nanoparticles (MSNs). Virus-based nanocarrier systems have also been rigorously investigated.

The nanoformulation of drug molecules has also gained rapid momentum over the past decade. As noted in the recent literature, gold and silver nanoparticles, even when stabilized by molecules such as tryptone (trypsinized casein) or citrate, can possess considerable therapeutic potential and display novel mechanisms of action. Furthermore, such nanoparticles can be functionalized with a variety of molecules, such as the polyphenols of medicinal herbs, antitumour natural products, etc., to improve their efficacy. Such therapeutics that possess dual mechanisms of action are called "biceuticals". Agents that act as therapeutics and serve as carriers for an equally or more effective drug molecule may be called pheroceuticals (from the Greek word, phérō – to carry). Moving one step further, the target specificity of such pheroceuticals can be enhanced by conjugating them with tumour-targeting antibodies or peptides. This special issue, entitled “Nanotechnology-Based Nanocarriers and Drug Delivery Systems”, highlights some of the most exciting and therapeutically relevant findings, supplying research articles and insightful reviews in nanomedicine research.

Dr. Manu Lopus
Guest Editor

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Keywords

  • nanomedicine
  • nanocarriers
  • biceuticals
  • pheroceuticals
  • cancer therapeutics
  • drug delivery

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Published Papers (6 papers)

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Research

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20 pages, 3492 KiB  
Article
Mechanistic of Vesicular Ethosomes and Elastic Liposomes on Permeation Profiles of Acyclovir across Artificial Membrane, Human Cultured EpiDerm, and Rat Skin: In Vitro-Ex Vivo Study
by Afzal Hussain, Mohammad A. Altamimi, Obaid Afzal, Abdulmalik S. A. Altamimi, Mohhammad Ramzan and Tahir Khuroo
Pharmaceutics 2023, 15(9), 2189; https://doi.org/10.3390/pharmaceutics15092189 - 24 Aug 2023
Cited by 2 | Viewed by 1418
Abstract
Acyclovir (ACV) controls cutaneous herpes, genital herpes, herpes keratitis, varicella zoster, and chickenpox. From previously reported ACV formulations, we continued to explore the permeation behavior of the optimized ACV loaded optimized ethosome (ETHO2R) and elastic liposome (ELP3R) and their respective carbopol gels across [...] Read more.
Acyclovir (ACV) controls cutaneous herpes, genital herpes, herpes keratitis, varicella zoster, and chickenpox. From previously reported ACV formulations, we continued to explore the permeation behavior of the optimized ACV loaded optimized ethosome (ETHO2R) and elastic liposome (ELP3R) and their respective carbopol gels across artificial membrane, cultured human EpiDerm, and rat skin. Transepidermal water loss (TEWL), scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and atomic force microscopy (AFM) were used to investigate the mechanistic perspective of permeation behavior. The size values of reformulated ELP3-R and ETHO2-R were observed as 217 and 128 nm, respectively (close to previous report), whereas their respective gels showed as 231 and 252 nm, respectively. ETHO2R showed high elasticity, %EE, and low vesicle size. These were investigated for the diffusion rate of the drug permeation (3 h) across the artificial membrane, cultured human EpiDerm, and rat skin. ETHO2GR showed the highest permeation flux (78.42 µg/cm2/h), diffusion coefficient (8.24 × 10−5 cm2/h), and permeation coefficient (0.67 × 10−3 cm/h) of ACV across synthetic membrane, whereas diffusion coefficient (2.4 × 10−4 cm2/h) and permeation coefficient (0.8 × 10−3 cm/h) were maximum across EpiDerm for ETHO2GR. ETHO2R suspension showed maximized permeation flux (169.58 µg/cm2/h) and diffusion rate (0.293 mg/cm2/h1/2), suggesting the rapid internalization of vesicles with cultured skin cells at low viscosity. A similar observation was revealed using rat skin, wherein the permeation flux (182.42 µg/cm2/h), permeation coefficient (0.3 × 10−2 cm/h), and diffusion rate (0.315 mg/cm2/h1/2) of ETHO2R were relatively higher than ELP3R and ELP3GR. Relative small size (128 nm), low viscosity, ethanol-mediated ultra-deformability, high drug entrapment (98%), and elasticity (63.2) are associated with ETHO2R to provide remarkable permeation behavior across the three barriers. The value of TEWL for ETHO2R (21.9 g/m2h) was 3.71 times higher than untreated control (5.9 g/m2h), indicating ethanol-mediated maximized surficial skin lipid perturbation at 3 h of application, whereas the respective ETHO2GR-treated rat skin had TEWL value (18.6 g/m2h) slightly lower than ETHO2R due to gel-based hydration into the skin. SEL, CLSM, and AFM provided a mechanistic perspective of ETHO2R and ELP3R-mediated permeation across rat skin and carrier-mediated visualization (skin–vesicle interaction). AFM provided detailed nanoscale surface roughness topographical parameters of treated and untreated rat skin as supportive data to SEM and CLSM. Thus, ethosomes ETHO2R and respective gel assisted maximum permeation of ACV across rat skin and cultured human EpiDerm to control cutaneous herpes infection and herpes keratitis. Full article
(This article belongs to the Special Issue Nanotechnology-Based Drug Formulations and Drug Delivery Systems)
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13 pages, 2461 KiB  
Article
Sodium Alginate/Chitosan-Coated Liposomes for Oral Delivery of Hydroxy-α-Sanshool: In Vitro and In Vivo Evaluation
by Fengming Tan, Huan Li, Kai Zhang, Lulu Xu, Dahan Zhang, Yang Han and Jing Han
Pharmaceutics 2023, 15(7), 2010; https://doi.org/10.3390/pharmaceutics15072010 - 24 Jul 2023
Cited by 4 | Viewed by 1949
Abstract
Background: Hydroxy-α-Sanshool (HAS) possesses various pharmacological properties, such as analgesia and regulating gastrointestinal function. However, the low oral bioavailability of HAS has limited its oral delivery in clinical application. Methods and Results: To enhance its oral bioavailability, a nanocomposite delivery system based on [...] Read more.
Background: Hydroxy-α-Sanshool (HAS) possesses various pharmacological properties, such as analgesia and regulating gastrointestinal function. However, the low oral bioavailability of HAS has limited its oral delivery in clinical application. Methods and Results: To enhance its oral bioavailability, a nanocomposite delivery system based on chitosan (CH, as the polycation) and sodium alginate (SA, as the polyanion) was prepared using a layer-by-layer coating technique. The morphology, thermal behavior and Fourier transform infrared spectrum (FTIR) showed that the obtained sodium alginate/chitosan-coated HAS-loaded liposomes (SA/CH-HAS-LIP) with core-shell structures have been successfully covered with polymers. When compared with HAS-loaded liposomes (HAS-LIP), SA/CH-HAS-LIP displayed obvious pH sensitivity and a sustained-release behavior in in vitro studies, which fitted well to Weibull model. In vivo, the half-life of HAS from SA/CH-HAS-LIP remarkably extended after oral administration compared to the free drug. Additionally, it allowed a 4.6-fold and 4.2-fold increase in oral bioavailability, respectively, compared with free HAS and HAS-LIP. Conclusions: SA/CH-HAS-LIP could be a promising release vehicle for the oral delivery of HAS to increase its oral bioavailability. Full article
(This article belongs to the Special Issue Nanotechnology-Based Drug Formulations and Drug Delivery Systems)
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19 pages, 7474 KiB  
Article
A γ-Glutamyl Transpeptidase (GGT)-Triggered Charge Reversal Drug-Delivery System for Cervical Cancer Treatment: In Vitro and In Vivo Investigation
by Jingxin Fu, Likang Lu, Manzhen Li, Yaoyao Guo, Meihua Han, Yifei Guo and Xiangtao Wang
Pharmaceutics 2023, 15(5), 1335; https://doi.org/10.3390/pharmaceutics15051335 - 25 Apr 2023
Cited by 7 | Viewed by 1949
Abstract
Neutral/negatively charged nanoparticles are beneficial to reduce plasma protein adsorption and prolong their blood circulation time, while positively charged nanoparticles easily transverse the blood vessel endothelium into a tumor and easily penetrate the depth of the tumor via transcytosis. Γ-Glutamyl transpeptidase (GGT) is [...] Read more.
Neutral/negatively charged nanoparticles are beneficial to reduce plasma protein adsorption and prolong their blood circulation time, while positively charged nanoparticles easily transverse the blood vessel endothelium into a tumor and easily penetrate the depth of the tumor via transcytosis. Γ-Glutamyl transpeptidase (GGT) is overexpressed on the external surface of endothelial cells of tumor blood vessels and metabolically active tumor cells. Nanocarriers modified by molecules containing γ-glutamyl moieties (such as glutathione, G-SH) can maintain a neutral/negative charge in the blood, as well as can be easily hydrolyzed by the GGT enzymes to expose the cationic surface at the tumor site, thus achieving good tumor accumulation via charge reversal. In this study, DSPE-PEG2000-GSH (DPG) was synthesized and used as a stabilizer to generate paclitaxel (PTX) nanosuspensions for the treatment of Hela cervical cancer (GGT-positive). The obtained drug-delivery system (PTX-DPG nanoparticles) was 164.6 ± 3.1 nm in diameter with a zeta potential of −9.85 ± 1.03 mV and a high drug-loaded content of 41.45 ± 0.7%. PTX-DPG NPs maintained their negative surface charge in a low concentration of GGT enzyme (0.05 U/mL), whereas they showed a significant charge-reversal property in the high-concentration solution of GGT enzyme (10 U/mL). After intravenous administration, PTX-DPG NPs mainly accumulated more in the tumor than in the liver, achieved good tumor-targetability, and significantly improved anti-tumor efficacy (68.48% vs. 24.07%, tumor inhibition rate, p < 0.05 in contrast to free PTX). This kind of GGT-triggered charge-reversal nanoparticle is promising to be a novel anti-tumor agent for the effective treatment of such GGT-positive cancers as cervical cancer. Full article
(This article belongs to the Special Issue Nanotechnology-Based Drug Formulations and Drug Delivery Systems)
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14 pages, 3339 KiB  
Article
Biomimetic Boron Nitride Nanoparticles for Targeted Drug Delivery and Enhanced Antitumor Activity
by Hui Li, Wei Qiao, Yizhe Shen, Huashan Xu, Yuan Fan, Yuxiang Liu, Yadi Lan, Yan Gong, Fuxue Chen and Shini Feng
Pharmaceutics 2023, 15(4), 1269; https://doi.org/10.3390/pharmaceutics15041269 - 18 Apr 2023
Cited by 6 | Viewed by 2099
Abstract
Boron nitride nanomaterials are being increasingly recognized as vehicles for cancer drug delivery that increase drug loading and control drug release because of their excellent physicochemical properties and biocompatibility. However, these nanoparticles are often cleared rapidly by the immune system and have poor [...] Read more.
Boron nitride nanomaterials are being increasingly recognized as vehicles for cancer drug delivery that increase drug loading and control drug release because of their excellent physicochemical properties and biocompatibility. However, these nanoparticles are often cleared rapidly by the immune system and have poor tumor targeting effects. As a result, biomimetic nanotechnology has emerged to address these challenges in recent times. Cell-derived biomimetic carriers have the characteristics of good biocompatibility, long circulation time, and strong targeting ability. Here, we report a biomimetic nanoplatform (CM@BN/DOX) prepared by encapsulating boron nitride nanoparticles (BN) and doxorubicin (DOX) together using cancer cell membrane (CCM) for targeted drug delivery and tumor therapy. The CM@BN/DOX nanoparticles (NPs) were able to target cancer cells of the same type on its own initiative through homologous targeting of cancer cell membranes. This led to a remarkable increase in cellular uptake. In vitro simulation of an acidic tumor microenvironment could effectively promote drug release from CM@BN/DOX. Furthermore, the CM@BN/DOX complex exhibited an excellent inhibitory effect against homotypic cancer cells. These findings suggest that CM@BN/DOX are promising in targeted drug delivery and potentially personalized therapy against their homologous tumor. Full article
(This article belongs to the Special Issue Nanotechnology-Based Drug Formulations and Drug Delivery Systems)
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18 pages, 6938 KiB  
Article
Mitochondrial-Targeted Triphenylphosphonium–Hydroxycamptothecin Conjugate and Its Nano-Formulations for Breast Cancer Therapy: In Vitro and In Vivo Investigation
by Kunfeng Zhang, Jingxin Fu, Xiaorui Liu, Yifei Guo, Meihua Han, Meifeng Liu and Xiangtao Wang
Pharmaceutics 2023, 15(2), 388; https://doi.org/10.3390/pharmaceutics15020388 - 24 Jan 2023
Cited by 4 | Viewed by 2734
Abstract
Mitochondria are involved in various stages of cancer cell diffusion and metastasis. Therefore, targeting tumor mitochondria with antineoplastic medicines to cause mitochondria to initiate apoptosis may be an effective strategy for cancer therapy. Here, in order to enhance the anti-tumor efficacy of the [...] Read more.
Mitochondria are involved in various stages of cancer cell diffusion and metastasis. Therefore, targeting tumor mitochondria with antineoplastic medicines to cause mitochondria to initiate apoptosis may be an effective strategy for cancer therapy. Here, in order to enhance the anti-tumor efficacy of the antineoplastic agent hydroxycamptothecin (HCPT), the mitochondrial targeting ligand 4-(carboxybutyl) triphenylphosphine bromide (TPP) was attached to HCPT by an ester linkage. The resultant TPP-HCPT (TH) conjugate could self-assemble into nano-aggregates, with a mean particle size of 203.2 nm and a polydispersity index (PDI) value of 0.312. The TH conjugate could also co-assembly with mPEG3000-PLGA5000 into nanoparticles (TH-NPs), with a mean diameter of 86.41 nm, a PDI value of 0.256 and a zeta potential of −0.125 mV. In contrast to HCPT injections, TH aggregates displayed enhanced cellular uptake, mitochondria-targetability and cytotoxicity against 4T1 cells, while TH-NPs showed even better improvement than TH aggregates. In the in vivo study, TH aggregates displayed higher anti-tumor efficacy in 4T1 tumor-bearing mice than HCPT injections (tumor inhibition rate, 55.71% vs. 69.17%), and TH-NPs displayed more superior anti-tumor effects (tumor inhibition rate, 80.02%). In conclusion, our research demonstrated that the TPP-HCPT conjugate and its nano-formulations, including TH aggregates and TH-NPs, may be a promising mitochondria-targeting anticancer medicine for cancer therapy. As far as we know, this is the first report in which TPP and HCPT have been conjugated directly for this aim. Full article
(This article belongs to the Special Issue Nanotechnology-Based Drug Formulations and Drug Delivery Systems)
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Review

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17 pages, 950 KiB  
Review
Experimental Methods for the Biological Evaluation of Nanoparticle-Based Drug Delivery Risks
by Ramendra Pati Pandey, Jasmina Vidic, Riya Mukherjee and Chung-Ming Chang
Pharmaceutics 2023, 15(2), 612; https://doi.org/10.3390/pharmaceutics15020612 - 11 Feb 2023
Cited by 11 | Viewed by 3350
Abstract
Many novel medical therapies use nanoparticle-based drug delivery systems, including nanomaterials through drug delivery systems, diagnostics, or physiologically active medicinal products. The approval of nanoparticles with advanced therapeutic and diagnostic potentials for applications in medication and immunization depends strongly on their synthesizing procedure, [...] Read more.
Many novel medical therapies use nanoparticle-based drug delivery systems, including nanomaterials through drug delivery systems, diagnostics, or physiologically active medicinal products. The approval of nanoparticles with advanced therapeutic and diagnostic potentials for applications in medication and immunization depends strongly on their synthesizing procedure, efficiency of functionalization, and biological safety and biocompatibility. Nanoparticle biodistribution, absorption, bioavailability, passage across biological barriers, and biodistribution are frequently assessed using bespoke and biological models. These methods largely rely on in vitro cell-based evaluations that cannot predict the complexity involved in preclinical and clinical studies. Therefore, assessing the nanoparticle risk has to involve pharmacokinetics, organ toxicity, and drug interactions manifested at multiple cellular levels. At the same time, there is a need for novel approaches to examine nanoparticle safety risks due to increased constraints on animal exploitation and the demand for high-throughput testing. We focus here on biological evaluation methodologies that provide access to nanoparticle interactions with the organism (positive or negative via toxicity). This work aimed to provide a perception regarding the risks associated with the utilization of nanoparticle-based formulations with a particular focus on assays applied to assess the cytotoxicity of nanomaterials. Full article
(This article belongs to the Special Issue Nanotechnology-Based Drug Formulations and Drug Delivery Systems)
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