Research

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22 pages, 19853 KiB

Open AccessArticle

Co-Delivery of Loxoprofen and Tofacitinib by Photothermal Microneedles for Rheumatoid Arthritis Treatment

by Yi Lu, Ting Xiao, Rongrong Lai, Ziyi Liu, Weixuan Luo, Yixuan Wang, Shijia Fu, Guihong Chai, Jinjing Jia and Yuehong Xu

Pharmaceutics 2023, 15(5), 1500; https://doi.org/10.3390/pharmaceutics15051500 - 15 May 2023

Cited by 3 | Viewed by 1814

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease of synovial inflammation that affects populations worldwide. Transdermal drug delivery systems for treating RA have increased but remain challenging. We fabricated a dissolving microneedle (MN) system with photothermal (PT) polydopamine (PDA) to co-load the non-steroidal anti-inflammatory [...] Read more.

Rheumatoid arthritis (RA) is an autoimmune disease of synovial inflammation that affects populations worldwide. Transdermal drug delivery systems for treating RA have increased but remain challenging. We fabricated a dissolving microneedle (MN) system with photothermal (PT) polydopamine (PDA) to co-load the non-steroidal anti-inflammatory drug loxoprofen (Lox) and the Janus kinase inhibitor tofacitinib (Tof), with the aim of co-delivering Lox and Tof directly to the articular cavity, aided by the combination of MN and PT. In vitro and in vivo permeation studies showed that the PT MN significantly promoted drug permeation and retention in the skin. An in vivo visualization of the drug distribution in the articular cavity showed that the PT MN significantly promoted drug retention in the articular cavity. Importantly, compared to the intra-articular injection of Lox and Tof, the application of the PT MN to a carrageenan/kaolin-induced arthritis rat model exhibited superior performance in reducing joint swelling, muscle atrophy, and cartilage destruction. Furthermore, the PT MN downregulated the mRNA expression levels of proinflammatory cytokines, including TNF-α, IL-1β, iNOS, JAK2, JAK3, and STAT3. The results show that the PT MN transdermal co-delivery of Lox and Tof is a new synergetic therapy with high compliance and good therapeutic efficacy for RA. Full article

(This article belongs to the Special Issue New Trends for Transdermal and Dermal Delivery)

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18 pages, 3810 KiB

Open AccessArticle

Probing Pharmaceutical Strategies to Promote the Skin Delivery of Asiatic Acid from Hydrogels: Enhancement Effects of Organic Amine Counterions, Chemical Enhancers, and Microneedle Pretreatment

by Mingming Li, Qiuyue Wang, Naiying Chen, Sicheng Yao, Xinxing Sun, Peng Quan and Yang Chen

Pharmaceutics 2022, 14(11), 2532; https://doi.org/10.3390/pharmaceutics14112532 - 20 Nov 2022

Cited by 4 | Viewed by 1591

Abstract

Asiatic acid (AA) is a pentacyclic triterpene isolated from Centella asiatica, holding great promise for treating a variety of skin disorders. However, the dermal application of AA is limited by its poor solubility and permeability. This study aimed to identify a hydrogel formulation [...] Read more.

Asiatic acid (AA) is a pentacyclic triterpene isolated from Centella asiatica, holding great promise for treating a variety of skin disorders. However, the dermal application of AA is limited by its poor solubility and permeability. This study aimed to identify a hydrogel formulation for AA and improve its skin penetration by various penetration enhancement methods. Four kinds of hydrogel bases were selected to prepare the AA hydrogel, in which different organic amines and chemical enhancers were incorporated in combination with microneedle pretreatment. The results showed that AA had good release profiles in the presence of hyaluronic acid as the hydrogel base and organic amines as the counter-ions. Diethylamine and Span 80 could promote drug penetration into the skin, and pretreatment with microneedles could further increase the drug permeability. In conclusion, the optimized hyaluronic acid hydrogel has great potential for use in the topical delivery of AA, and its penetration via the skin can be further improved by different pharmaceutical approaches. Full article

(This article belongs to the Special Issue New Trends for Transdermal and Dermal Delivery)

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25 pages, 2077 KiB

Open AccessArticle

Design, Formulation, and Characterization of Valsartan Nanoethosomes for Improving Their Bioavailability

by Ali M. Nasr, Fayrouz Moftah, Mohammed A. S. Abourehab and Shadeed Gad

Pharmaceutics 2022, 14(11), 2268; https://doi.org/10.3390/pharmaceutics14112268 - 24 Oct 2022

Cited by 11 | Viewed by 2045

Abstract

The objective of this study was to formulate and evaluate valsartan (VLT) ethosomes to prepare an optimized formula of VLT-entrapped ethosomes that could be incorporated into a sustained release transdermal gel dosage form. The formulation of the prepared ethosomal gel was investigated and [...] Read more.

The objective of this study was to formulate and evaluate valsartan (VLT) ethosomes to prepare an optimized formula of VLT-entrapped ethosomes that could be incorporated into a sustained release transdermal gel dosage form. The formulation of the prepared ethosomal gel was investigated and subjected to in vitro drug release studies, ex vivo test, and in vivo studies to assess the effectiveness of ethosomal formulation in enhancing the bioavailability of VLT as a poorly soluble drug and in controlling its release from the transdermal gel dosage form. The acquired results are as follows: Dependent responses were particle size, polydispersity index, zeta potential, and entrapment efficiency. The optimized VLT-ETHs had a nanometric diameter (45.8 ± 0.5 nm), a negative surface charge (−51.4 ± 6.3 mV), and a high drug encapsulation (94.24 ± 0.2). The prepared VLT ethosomal gel (VLT-ethogel) showed a high peak plasma concentration and enhanced bioavailability in rats compared with the oral solution of valsartan presented in the higher AUC (0–∞). The AUC (0–∞) with oral treatment was 7.0 ± 2.94 (μg.h/mL), but the AUC (0–∞) with topical application of the VAL nanoethosomal gel was 137.2 ± 49.88 (μg.h/mL), providing the sustained release pattern of VLT from the tested ethosomal gel. Full article

(This article belongs to the Special Issue New Trends for Transdermal and Dermal Delivery)

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14 pages, 9343 KiB

Open AccessArticle

Mechanistic Study of Release Characteristics of Two Active Ingredients in Transdermal Patch Containing Lidocaine−Flurbiprofen Ionic Liquid

by Degong Yang, Xuejun Chen, Ziqing Li and Chunrong Yang

Pharmaceutics 2022, 14(10), 2158; https://doi.org/10.3390/pharmaceutics14102158 - 10 Oct 2022

Cited by 3 | Viewed by 1505

Abstract

Ionic liquids (ILs) have been proven to be an efficient technology for enhancing drug skin permeability. However, the question of whether the two components of ILs are released synchronously in transdermal preparations has remained unclear. Thus, this study aimed to investigate the release [...] Read more.

Ionic liquids (ILs) have been proven to be an efficient technology for enhancing drug skin permeability. However, the question of whether the two components of ILs are released synchronously in transdermal preparations has remained unclear. Thus, this study aimed to investigate the release characteristics of two components of ILs and their underlying molecular mechanism. The ILs containing flurbiprofen (FLU) and lidocaine (LID) were synthesized and characterized. The four typical acrylates pressure sensitive adhesives (PSAs) with different functional groups were synthesized and characterized. The effects of PSAs on the release characteristics of two components of ILs were investigated by drug release tests and verified by skin permeation experiments. The action mechanisms were revealed by FTIR, Raman, dielectric spectrum, and molecular docking. The results showed that the average release amount of FLU (0.29 μmol/cm²) and LID (0.11 μmol/cm²) of ILs in the four PSAs was significantly different (p < 0.05), which illustrated that the two components did not release synchronously. The PSA−none and PSA−OH with low permittivity (7.37, 9.82) interacted with drugs mainly by dipole-dipole interactions and hydrogen bonds. The PSA−COOH and PSA−CONH₂ with high permittivity (11.19, 15.32) interacted with drugs mainly by ionic bonds and ionic hydrogen bonds. Thus, this study provides scientific guidance for the application of ILs in transdermal preparations. Full article

(This article belongs to the Special Issue New Trends for Transdermal and Dermal Delivery)

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14 pages, 3732 KiB

Open AccessArticle

Dual Antimelanogenic Effect of Nicotinamide-Stabilized Phloretin Nanocrystals in Larval Zebrafish

by Yixuan Li, Hong Xiang, Xinyue Xue, Yilan Chen, Zhiyuan He, Zhongrui Yu, Li Zhang and Xiaoqing Miao

Pharmaceutics 2022, 14(9), 1825; https://doi.org/10.3390/pharmaceutics14091825 - 30 Aug 2022

Cited by 8 | Viewed by 1919

Abstract

Melanin is a kind of dark insoluble pigment that can cause pigmentation and free-radical clearance, inducing melasma, freckles, and chloasma, affecting the quality of life of patients. Due to poor water solubility and low safety, the absorption of poorly water-soluble drugs is limited [...] Read more.

Melanin is a kind of dark insoluble pigment that can cause pigmentation and free-radical clearance, inducing melasma, freckles, and chloasma, affecting the quality of life of patients. Due to poor water solubility and low safety, the absorption of poorly water-soluble drugs is limited by the hinderance of a skin barrier. Therefore, it is necessary to develop new, safe, and highly efficient drugs to improve their transdermal absorption efficiency and thus to inhibit the production of melanin. To address these issues, we developed a new nicotinamide (NIC)-stabilized phloretin nanocrystals (PHL-NCs). First, NC technology significantly increased the solubility of PHL. The in vitro release results indicated that at 6 h, the dissolution of the PHL-NIC-NCs was 101.39% ± 2.40% and of the PHL-NCs was 84.92% ± 4.30%, while that of the physical mixture of the two drugs was only 64.43% ± 0.02%. Second, NIC acted not only as a stabilizer to enlarge the storage time of PHL-NIC-NCs (improved to 10-day in vitro stability) but also as a melanin transfer inhibitor to inhibit melanin production. Finally, we verified the melanin inhibition effect of PHL-NIC-NCs evaluated by the zebrafish model. It showed that 0.38 mM/L PHL-NIC-NCs have a lower tyrosinase activity at 62.97% ± 0.52% and have less melanin at 36.57% ± 0.44%. The inhibition effect of PHL-NCs and PHL-NIC-NCs was stronger compared to the positive control arbutin. In conclusion, the combination of NIC and PHL achieves better inhibition of tyrosinase and inhibition of melanin production through synergism. This will provide a direction to the subsequent development of melanin-inhibiting drugs and the combined use of pharmaceutical agents. Full article

(This article belongs to the Special Issue New Trends for Transdermal and Dermal Delivery)

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20 pages, 9414 KiB

Open AccessArticle

Upgrading the Transdermal Biomedical Capabilities of Thyme Essential Oil Nanoemulsions Using Amphiphilic Oligochitosan Vehicles

by Ali M. Nasr, Yasmin I. Mortagi, Nashwa H. Abd Elwahab, Mohammad Y. Alfaifi, Ali A. Shati, Serag Eldin I. Elbehairi, Reda F. M. Elshaarawy and Islam Kamal

Pharmaceutics 2022, 14(7), 1350; https://doi.org/10.3390/pharmaceutics14071350 - 25 Jun 2022

Cited by 13 | Viewed by 1535

Abstract

(1) Background: Thymus vulgaris L. (thyme) essential oil (TEO) has gained much attention because of its long history of medicinal usage. However, the lack of precise chemical profiling of the TEO and methods to optimize the bioactivity and delivery of its constituents has [...] Read more.

(1) Background: Thymus vulgaris L. (thyme) essential oil (TEO) has gained much attention because of its long history of medicinal usage. However, the lack of precise chemical profiling of the TEO and methods to optimize the bioactivity and delivery of its constituents has hampered its research on quality control and biological function; (2) Methods: The current study aimed to analyze the TEO’s chemical composition using the GC-MS method and identify its key components. Another objective of this work is to study the impact of the protective layer of amphiphilic oligochitosan (AOC) on the physicochemical stability and transdermal potentials of TEO multilayer nanoemulsions formulated by the incorporation of TEO, Tween80, lecithin (Lec), and AOC; (3) Results: The AOC protective layer significantly improved the stability of TEO-based NEs as revealed by the constancy of their physicochemical properties (particle size and zeta potential) during storage for a week. Excessive fine-tuning of thyme extract NEs and the AOC protective layer’s persistent positive charge have been contributed to the thyme extract’s improved anti-inflammatory, transdermal, and anti-melanoma potentials; (4) Conclusions: the AOC-coated NEs could offer novel multifunctional nanoplatforms for effective transdermal delivery of lipophilic bioactive materials. Full article

(This article belongs to the Special Issue New Trends for Transdermal and Dermal Delivery)

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Review

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27 pages, 4230 KiB

Open AccessReview

Revolutionizing Therapeutic Delivery with Microneedle Technology for Tumor Treatment

by Vaibhavi Meghraj Desai, Sakshi Priya, Srividya Gorantla and Gautam Singhvi

Pharmaceutics 2023, 15(1), 14; https://doi.org/10.3390/pharmaceutics15010014 - 21 Dec 2022

Cited by 6 | Viewed by 2508

Abstract

The tumor is an uncontrolled growth of tissue that can be localized (benign) or possesses the capability of metastasis (malignant). The conventional methods of tumor diagnosis, such as acupuncture, endoscopy, and histopathology, and treatment methods, such as injections, chemotherapy, surgery, and radiotherapy, are [...] Read more.

The tumor is an uncontrolled growth of tissue that can be localized (benign) or possesses the capability of metastasis (malignant). The conventional methods of tumor diagnosis, such as acupuncture, endoscopy, and histopathology, and treatment methods, such as injections, chemotherapy, surgery, and radiotherapy, are invasive, expensive, and pose severe safety and management issues for the patients. Microneedle technology is a recently developed approach for active transdermal drug delivery. It is minimally invasive, self-administrable, bypasses the first-pass effect, and effectively delivers chemotherapeutics and drugs at low doses, thus, overcoming the drawbacks of conventional delivery systems. This review provides an idea of the types, materials utilized in the fabrication, and techniques used for the preparation of microneedles (MNs), as well as their application in tumor diagnosis and treatment. Additionally, emphasis is given to the case studies related to MNs-assisted tumor therapy, such as photothermal therapy, gene therapy, photodynamic therapy, chemotherapy, immunotherapy, and various combination therapies. MNs also serve as a tool for diagnosis by the bio-sampling of blood and interstitial skin fluid, as well as biosensing various cancer biomarkers. The combined therapy and diagnostics provide theranostic MNs for enhanced and personalized tumor therapy. The limitations and prospects of MNs development are also discussed. Full article

(This article belongs to the Special Issue New Trends for Transdermal and Dermal Delivery)

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28 pages, 818 KiB

Open AccessReview

Promising Strategies for Transdermal Delivery of Arthritis Drugs: Microneedle Systems

by Jitong Wang, Jia Zeng, Zhidan Liu, Qin Zhou, Xin Wang, Fan Zhao, Yu Zhang, Jiamiao Wang, Minchen Liu and Ruofei Du

Pharmaceutics 2022, 14(8), 1736; https://doi.org/10.3390/pharmaceutics14081736 - 19 Aug 2022

Cited by 16 | Viewed by 4028

Abstract

Arthritis is a general term for various types of inflammatory joint diseases. The most common clinical conditions are mainly represented by rheumatoid arthritis and osteoarthritis, which affect more than 4% of people worldwide and seriously limit their mobility. Arthritis medication generally requires long-term [...] Read more.

Arthritis is a general term for various types of inflammatory joint diseases. The most common clinical conditions are mainly represented by rheumatoid arthritis and osteoarthritis, which affect more than 4% of people worldwide and seriously limit their mobility. Arthritis medication generally requires long-term application, while conventional administrations by oral delivery or injections may cause gastrointestinal side effects and are inconvenient for patients during long-term application. Emerging microneedle (MN) technology in recent years has created new avenues of transdermal delivery for arthritis drugs due to its advantages of painless skin perforation and efficient local delivery. This review summarizes various types of arthritis and current therapeutic agents. The current development of MNs in the delivery of arthritis drugs is highlighted, demonstrating their capabilities in achieving different drug release profiles through different self-enhancement methods or the incorporation of nanocarriers. Furthermore, the challenges of translating MNs from laboratory studies to the clinical practice and the marketplace are discussed. This promising technology provides a new approach to the current drug delivery paradigm in treating arthritis in transdermal delivery. Full article

(This article belongs to the Special Issue New Trends for Transdermal and Dermal Delivery)

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