Research

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13 pages, 1983 KiB

Open AccessArticle

Targeted c-Myc Inhibition and Systemic Temozolomide Therapy Extend Survival in Glioblastoma Xenografts

by Laxmi Dhungel, Cayla Harris, Lauren Romine, Jan Sarkaria and Drazen Raucher

Bioengineering 2023, 10(6), 718; https://doi.org/10.3390/bioengineering10060718 - 14 Jun 2023

Cited by 2 | Viewed by 1470

Glioblastoma is a highly aggressive disease with poor patient outcomes despite current treatment options, which consist of surgery, radiation, and chemotherapy. However, these strategies present challenges such as resistance development, damage to healthy tissue, and complications due to the blood–brain barrier. There is [...] Read more.

Glioblastoma is a highly aggressive disease with poor patient outcomes despite current treatment options, which consist of surgery, radiation, and chemotherapy. However, these strategies present challenges such as resistance development, damage to healthy tissue, and complications due to the blood–brain barrier. There is therefore a critical need for new treatment modalities that can selectively target tumor cells, minimize resistance development, and improve patient survival. Temozolomide is the current standard chemotherapeutic agent for glioblastoma, yet its use is hindered by drug resistance and severe side effects. Combination therapy using multiple drugs acting synergistically to kill cancer cells and with multiple targets can provide increased efficacy at lower drug concentrations and reduce side effects. In our previous work, we designed a therapeutic peptide (Bac-ELP1-H1) targeting the c-myc oncogene and demonstrated its ability to reduce tumor size, delay neurological deficits, and improve survival in a rat glioblastoma model. In this study, we expanded our research to the U87 glioblastoma cell line and investigated the efficacy of Bac-ELP1-H1/hyperthermia treatment, as well as the combination treatment of temozolomide and Bac-ELP1-H1, in suppressing tumor growth and extending survival in athymic mice. Our experiments revealed that the combination treatment of Bac-ELP1-H1 and temozolomide acted synergistically to enhance survival in mice and was more effective in reducing tumor progression than the single components. Additionally, our study demonstrated the effectiveness of hyperthermia in facilitating the accumulation of the Bac-ELP1-H1 protein at the tumor site. Our findings suggest that the combination of targeted c-myc inhibitory biopolymer with systemic temozolomide therapy may represent a promising alternative treatment option for glioblastoma patients. Full article

(This article belongs to the Special Issue Drug Delivery Systems, What's New?)

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13 pages, 5187 KiB

Open AccessEditor’s ChoiceArticle

Portable Iontophoresis Device for Efficient Drug Delivery

by Moonjeong Bok, Young Il Kwon, Zheng Min Huang and Eunju Lim

Bioengineering 2023, 10(1), 88; https://doi.org/10.3390/bioengineering10010088 - 09 Jan 2023

Viewed by 2704

Abstract

The timely delivery of drugs to specific locations in the body is imperative to ensure the efficacy of treatment. This study introduces a portable facial device that can deliver drugs efficiently using iontophoresis. Two types of power supplies—direct current and pulse ionization supplies—were [...] Read more.

The timely delivery of drugs to specific locations in the body is imperative to ensure the efficacy of treatment. This study introduces a portable facial device that can deliver drugs efficiently using iontophoresis. Two types of power supplies—direct current and pulse ionization supplies—were manufactured by injection molding. Electrical stimulation elements, which contained Ag metal wires, were woven into facial mask packs. The diffusion phenomenon in the skin and iontophoresis were numerically modeled. Injection molding was simulated before the device was manufactured. Analysis using rhodamine B demonstrated a remarkable increase in the moisture content of the skin and effective absorption of the drug under an applied electric field upon the application of iontophoresis. The proposed concept and design constitute a new method of achieving effective drug absorption with wearable devices. Full article

(This article belongs to the Special Issue Drug Delivery Systems, What's New?)

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16 pages, 4456 KiB

Open AccessArticle

Synthesis of Carrier-Free Paclitaxel–Curcumin Nanoparticles: The Role of Curcuminoids

by Sena Karaosmanoglu, Yunsen Zhang, Wenli Zhou, Defang Ouyang and Xianfeng Chen

Bioengineering 2022, 9(12), 815; https://doi.org/10.3390/bioengineering9120815 - 18 Dec 2022

Cited by 1 | Viewed by 1752

Abstract

The systemic administration of paclitaxel (PTX)-based combinatorial therapies is significantly restricted due to the multidrug resistance. Curcumin (CUR) not only inhibits cancer-cell proliferation but also reverses the PTX resistance. However, achieving codelivery of these two drugs is a challenge due to their poor [...] Read more.

The systemic administration of paclitaxel (PTX)-based combinatorial therapies is significantly restricted due to the multidrug resistance. Curcumin (CUR) not only inhibits cancer-cell proliferation but also reverses the PTX resistance. However, achieving codelivery of these two drugs is a challenge due to their poor water solubility. Herein, we synthesized carrier-free PTX NPs by a facile nanoprecipitation method with the help of CUR and other curcuminoids present in turmeric extract. The prepared NPs demonstrated spherical morphologies with high conformational stability. Experimental studies showed that the presence of both bisdemethoxycurcumin and demethoxycurcumin is essential for the successful formation of spherical and monodisperse NPs. Computational studies revealed that the presence of the more sterically available curcuminoids BMC and DMC makes the self-assembly procedure more adaptable with a higher number of potential conformations that could give rise to more monodisperse PTX-CUR NPs. Compared with PTX alone, PTX-CUR NPs have shown comparable therapeutic efficiency in vitro and demonstrated a higher cellular internalization, highlighting their potential for in vivo applications. The successful formation of PTX-CUR NPs and the understanding of how multiple drugs behave at the molecular level also provide guidance for developing formulations for the synthesis of high-quality and effective carrier-free nanosystems for biomedical applications. Full article

(This article belongs to the Special Issue Drug Delivery Systems, What's New?)

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16 pages, 4617 KiB

Open AccessArticle

Meta-Analysis: A Convenient Tool for the Choice of Nose-to-Brain Nanocarriers

by Rania M. Hathout and Eman M. El-Marakby

Bioengineering 2022, 9(11), 647; https://doi.org/10.3390/bioengineering9110647 - 03 Nov 2022

Cited by 2 | Viewed by 1217

Abstract

Objectives: The intranasal route represents a high promising route of administration aiming for brain delivery. Yet, it represents one of the most difficult and complicated routes. Accordingly, scientists are in a continuous search for novel drug delivery vehicles such as the lipid and [...] Read more.

Objectives: The intranasal route represents a high promising route of administration aiming for brain delivery. Yet, it represents one of the most difficult and complicated routes. Accordingly, scientists are in a continuous search for novel drug delivery vehicles such as the lipid and polymeric nanoparticles that are apt to enhance the bioavailability of the administered drugs to reach the brain. In this study, a certain number of publications were selected from different databases and literature. Meta-analysis studies using two different algorithms (DerSimonian–Laird and inverse variance) followed aiming to explore the published studies and confirm by evidence the superiority of nanocarriers in enhancing the brain bioavailability of various drugs. Furthermore, the quantitative comparison of lipid versus polymeric nanosystems was performed. Methods: The area under the curve (AUC) as an important pharmacokinetic parameter extracted from in vivo animal studies was designated as the “effect” in the performed meta-analysis after normalization. Forest plots were generated. Key findings and Conclusions: The meta-analysis confirmed the augmentation of the AUC after the comparison with traditional preparations such as solutions and suspensions. Most importantly, lipid nanoparticles were proven to be significantly superior to the polymeric counterparts. Full article

(This article belongs to the Special Issue Drug Delivery Systems, What's New?)

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17 pages, 1970 KiB

Open AccessArticle

Investigation of Factors Influencing Formation of Nanoemulsion by Spontaneous Emulsification: Impact on Droplet Size, Polydispersity Index, and Stability

by Mohammed S. Algahtani, Mohammad Zaki Ahmad and Javed Ahmad

Bioengineering 2022, 9(8), 384; https://doi.org/10.3390/bioengineering9080384 - 12 Aug 2022

Cited by 11 | Viewed by 2331

Abstract

Interest in nanoemulsion technology has increased steadily in recent years for its widespread applications in the delivery of pharmaceuticals, nutraceuticals, and cosmeceuticals. Rational selection of the composition and the preparation method is crucial for developing a stable nanoemulsion system with desired physicochemical characteristics. [...] Read more.

Interest in nanoemulsion technology has increased steadily in recent years for its widespread applications in the delivery of pharmaceuticals, nutraceuticals, and cosmeceuticals. Rational selection of the composition and the preparation method is crucial for developing a stable nanoemulsion system with desired physicochemical characteristics. In the present study, we investigate the influence of intricate factors including composition and preparation conditions that affect characteristic parameters and the stability of the nanoemulsion formation prepared by the spontaneous emulsification method. Octanoic acid, capryol 90, and ethyl oleate were selected to represent oil phases of different carbon–chain lengths. We explored the impact of the addition mode of the oil–S_mix phase and aqueous phase, vortexing time, K_m (surfactant/cosurfactant) ratio, and the replacement of water by buffers of different pH as an aqueous system. The phase behavior study showed that the S_mix phase had a significant impact on the nanoemulsifying ability of the nanoemulsions composed of oil phases of varying carbon-chain lengths. The mode of mixing of the oil–S_mix phase to the aqueous phase markedly influenced the mean droplet size and size distribution of the nanoemulsions composed of oil phases as capryol 90. Vortexing time also impacted the mean droplet size and the stability of the generated nanoemulsion system depending on the varying carbon-chain length of the oil phase. The replacement of the water phase by aqueous buffers of pH 1.2, 5.5, 6.8, and 7.4 has altered the mean droplet size and size distribution of the nanoemulsion system. Further, the K_m ratio also had a significant influence on the formation of the nanoemulsion system. The findings of this investigation are useful in understanding how the formulation composition and process parameters of the spontaneous emulsification technique are responsible for affecting the physicochemical characteristics and stability of the nanoemulsion system composed of oil of varying carbon-chain (C₈-C₁₈) length. Full article

(This article belongs to the Special Issue Drug Delivery Systems, What's New?)

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10 pages, 2965 KiB

Open AccessArticle

Preparation of Polyvinylidene Fluoride–Gold Nanoparticles Electrospinning Nanofiber Membranes

by Xuemei Ge, Shang Wu, Wen Shen, Lijuan Chen, Yan Zheng, Fen Ao, Yuanlan Ning, Yueyang Mao and Zhong Chen

Bioengineering 2022, 9(4), 130; https://doi.org/10.3390/bioengineering9040130 - 24 Mar 2022

Cited by 4 | Viewed by 2329

Abstract

In this work, gold nanoparticles (AuNPs) and curcumin drug were incorporated in polyvinylidene fluoride (PVDF) nanofibers by electrospinning as a novel tissue engineering scaffold in nerve regeneration. The influence of AuNPs on the morphology, crystallinity, and drug release behavior of nanofiber membranes was [...] Read more.

In this work, gold nanoparticles (AuNPs) and curcumin drug were incorporated in polyvinylidene fluoride (PVDF) nanofibers by electrospinning as a novel tissue engineering scaffold in nerve regeneration. The influence of AuNPs on the morphology, crystallinity, and drug release behavior of nanofiber membranes was characterized. A successful composite nanofiber membrane sample was observed by scanning electron microscopy (SEM). The addition of AuNPs showed the improved as well as prolonged cumulative release of the drug. The results indicated that PVDF–AuNPs nanofiber membrane could potentially be applied for nerve regeneration. Full article

(This article belongs to the Special Issue Drug Delivery Systems, What's New?)

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Review

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22 pages, 3425 KiB

Open AccessReview

Towards Novel Biomimetic In Vitro Models of the Blood–Brain Barrier for Drug Permeability Evaluation

by Inés Mármol, Sara Abizanda-Campo, Jose M. Ayuso, Ignacio Ochoa and Sara Oliván

Bioengineering 2023, 10(5), 572; https://doi.org/10.3390/bioengineering10050572 - 10 May 2023

Cited by 2 | Viewed by 2616

Abstract

Current available animal and in vitro cell-based models for studying brain-related pathologies and drug evaluation face several limitations since they are unable to reproduce the unique architecture and physiology of the human blood–brain barrier. Because of that, promising preclinical drug candidates often fail [...] Read more.

Current available animal and in vitro cell-based models for studying brain-related pathologies and drug evaluation face several limitations since they are unable to reproduce the unique architecture and physiology of the human blood–brain barrier. Because of that, promising preclinical drug candidates often fail in clinical trials due to their inability to penetrate the blood–brain barrier (BBB). Therefore, novel models that allow us to successfully predict drug permeability through the BBB would accelerate the implementation of much-needed therapies for glioblastoma, Alzheimer’s disease, and further disorders. In line with this, organ-on-chip models of the BBB are an interesting alternative to traditional models. These microfluidic models provide the necessary support to recreate the architecture of the BBB and mimic the fluidic conditions of the cerebral microvasculature. Herein, the most recent advances in organ-on-chip models for the BBB are reviewed, focusing on their potential to provide robust and reliable data regarding drug candidate ability to reach the brain parenchyma. We point out recent achievements and challenges to overcome in order to advance in more biomimetic in vitro experimental models based on OOO technology. The minimum requirements that should be met to be considered biomimetic (cellular types, fluid flow, and tissular architecture), and consequently, a solid alternative to in vitro traditional models or animals. Full article

(This article belongs to the Special Issue Drug Delivery Systems, What's New?)

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30 pages, 4509 KiB

Open AccessReview

Experimental Models to Study the Functions of the Blood–Brain Barrier

by Andrzej Łach, Agnieszka Wnuk and Anna Katarzyna Wójtowicz

Bioengineering 2023, 10(5), 519; https://doi.org/10.3390/bioengineering10050519 - 25 Apr 2023

Cited by 2 | Viewed by 2318

Abstract

The purpose of this paper was to discuss the achievements of in vitro modeling in terms of the blood–brain barrier [BBB] and to create a clear overview of this research area, which is useful in research planning. The text was divided into three [...] Read more.

The purpose of this paper was to discuss the achievements of in vitro modeling in terms of the blood–brain barrier [BBB] and to create a clear overview of this research area, which is useful in research planning. The text was divided into three main parts. The first part describes the BBB as a functional structure, its constitution, cellular and noncellular components, mechanisms of functioning and importance for the central nervous system, in terms of both protection and nourishment. The second part is an overview of parameters important in terms of establishing and maintaining a barrier phenotype that allows for formulating criteria of evaluation of the BBB in vitro models. The third and last part discusses certain techniques for developing the BBB in vitro models. It describes subsequent research approaches and models, as they underwent change alongside technological advancement. On the one hand, we discuss possibilities and limitations of different research approaches: primary cultures vs. cell lines and monocultures vs. multicultures. On the other hand, we review advantages and disadvantages of specific models, such as models-on-a-chip, 3D models or microfluidic models. We not only attempt to state the usefulness of specific models in different kinds of research on the BBB but also emphasize the significance of this area of research for advancement of neuroscience and the pharmaceutical industry. Full article

(This article belongs to the Special Issue Drug Delivery Systems, What's New?)

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20 pages, 1561 KiB

Open AccessReview

Anticancer Activity, Mechanism, and Delivery of Allyl Isothiocyanate

by Ammar Tarar, Sarah Peng, Soha Cheema and Ching-An Peng

Bioengineering 2022, 9(9), 470; https://doi.org/10.3390/bioengineering9090470 - 14 Sep 2022

Cited by 4 | Viewed by 2334

Abstract

Allyl isothiocyanate (AITC) is a phytochemical that is abundantly present in cruciferous vegetables of the Brassicaceae family, such as cabbage, broccoli, mustard, wasabi, and cauliflower. The pungent taste of these vegetables is mainly due to the content of AITC present in these vegetables. [...] Read more.

Allyl isothiocyanate (AITC) is a phytochemical that is abundantly present in cruciferous vegetables of the Brassicaceae family, such as cabbage, broccoli, mustard, wasabi, and cauliflower. The pungent taste of these vegetables is mainly due to the content of AITC present in these vegetables. AITC is stored stably in the plant as its precursor sinigrin (a type of glucosinolate), which is physically separated from myrosin cells containing myrosinase. Upon tissue disruption, myrosinase gets released and hydrolyzes the sinigrin to produce AITC and by-products. AITC is an organosulfur compound, both an irritant and toxic, but it carries pharmacological properties, including anticancer, antibacterial, antifungal, and anti-inflammatory activities. Despite the promising anticancer effectiveness of AITC, its clinical application still possesses challenges due to several factors, i.e., low aqueous solubility, instability, and low bioavailability. In this review, the anticancer activity of AITC against several cancer models is summarized from the literature. Although the mechanism of action is still not fully understood, several pathways have been identified; these are discussed in this review. Not much attention has been given to the delivery of AITC, which hinders its clinical application. However, the few studies that have demonstrated the use of nanotechnology to facilitate the delivery of AITC are addressed. Full article

(This article belongs to the Special Issue Drug Delivery Systems, What's New?)

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22 pages, 1929 KiB

Open AccessReview

Microemulsions and Nanoemulsions in Skin Drug Delivery

by Eliana B. Souto, Amanda Cano, Carlos Martins-Gomes, Tiago E. Coutinho, Aleksandra Zielińska and Amélia M. Silva

Bioengineering 2022, 9(4), 158; https://doi.org/10.3390/bioengineering9040158 - 05 Apr 2022

Cited by 73 | Viewed by 8732

Abstract

Microemulsions and nanoemulsions are lipid-based pharmaceutical systems with a high potential to increase the permeation of drugs through the skin. Although being isotropic dispersions of two nonmiscible liquids (oil and water), significant differences are encountered between microemulsions and nanoemulsions. Microemulsions are thermodynamically stable [...] Read more.

Microemulsions and nanoemulsions are lipid-based pharmaceutical systems with a high potential to increase the permeation of drugs through the skin. Although being isotropic dispersions of two nonmiscible liquids (oil and water), significant differences are encountered between microemulsions and nanoemulsions. Microemulsions are thermodynamically stable o/w emulsions of mean droplet size approximately 100–400 nm, whereas nanoemulsions are thermodynamically unstable o/w emulsions of mean droplet size approximately 1 to 100 nm. Their inner oil phase allows the solubilization of lipophilic drugs, achieving high encapsulation rates, which are instrumental for drug delivery. In this review, the importance of these systems, the key differences regarding their composition and production processes are discussed. While most of the micro/nanoemulsions on the market are held by the cosmetic industry to enhance the activity of drugs used in skincare products, the development of novel pharmaceutical formulations designed for the topical, dermal and transdermal administration of therapeutic drugs is being considered. The delivery of poorly water-soluble molecules through the skin has shown some advantages over the oral route, since drugs escape from first-pass metabolism; particularly for the treatment of cutaneous diseases, topical delivery should be the preferential route in order to reduce the number of drugs used and potential side-effects, while directing the drugs to the site of action. Thus, nanoemulsions and microemulsions represent versatile options for the delivery of drugs through lipophilic barriers, and many synthetic and natural compounds have been formulated using these delivery systems, aiming to improve stability, delivery and bioactivity. Detailed information is provided concerning the most relevant recent scientific publications reporting the potential of these delivery systems to increase the skin permeability of drugs with anti-inflammatory, sun-protection, anticarcinogenic and/or wound-healing activities. The main marketed skincare products using emulsion-based systems are also presented and discussed. Full article

(This article belongs to the Special Issue Drug Delivery Systems, What's New?)

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