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Pharmaceutics
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Liposomes for Transmucosal Drug Delivery
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Liposomes for Transmucosal Drug Delivery

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 (10 February 2023) | Viewed by 11906

Special Issue Editors

Prof. Dr. Amparo Sánchez Navarro

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Salamanca, 37007 Salamanca, Spain
Interests: drug delivery; liposomes; solvent-free procedures; lyophilization; pulmonary formulations; transmucosal drug delivery
Dr. María José de Jesús Valle

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Salamanca, 37007 Salamanca, Spain
Interests: drug delivery; liposomes; solvent-free procedures; lyophilization; pulmonary formulations; transmucosal drug delivery

Special Issue Information

Dear Colleagues,

Liposomes are safe and biocompatible vesicular nanosystems that can incorporate hydrophilic, hydrophobic and amphiphilic small molecules, as well as macromolecules, nanoparticulates, or bacterial and virus material. With different sizes and surface properties, these versatile vesicles have a huge potential as nanocarriers to overcome body barriers. Transmucosal administration is an alternative route for a great variety of medications. Ocular infections, glaucoma, macular degeneration, dry eye or corneal pain demand innovative medicines able to cross ocular barriers. Drug inhalation is a challenge for the systemic delivery of therapeutic proteins, as well as passive targeting for pulmonary diseases such as cancer or hypertension. Nose-to-brain delivery is proposed for treatment of Alzheimer’s, Huntington’s or Parkinson´s diseases. The development of sustained local delivery at the buccal, nasal, vaginal, gastrointestinal or vesical cavity is in high demand for many drugs. On top of that, liposomal vectors for DNA, mRNA and other types of vaccines intended for transmucosal delivery are highly sought after. Liposomal formulations may incorporate a great variety of active compounds and transport them from the mucous membrane to the target site.

This Special Issue aims to highlight current progress in the development of liposomes for the transmucosal delivery of drugs and vaccines.

Prof. Dr. Amparo Sánchez Navarro
Dr. María José de Jesús Valle
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

  • liposomes
  • transmucosal delivery
  • ocular delivery
  • nose-to-brain
  • pulmonary delivery
  • buccal delivery
  • vaginal delivery 
  • lipid vectors

Published Papers (5 papers)

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Research

20 pages, 5082 KiB  
Article
Baricitinib Liposomes as a New Approach for the Treatment of Sjögren’s Syndrome
by Núria Garrós, Mireia Mallandrich, Negar Beirampour, Roya Mohammadi, Òscar Domènech, Maria José Rodríguez-Lagunas, Beatriz Clares and Helena Colom
Pharmaceutics 2022, 14(9), 1895; https://doi.org/10.3390/pharmaceutics14091895 - 07 Sep 2022
Cited by 6 | Viewed by 1990
Abstract
Sjögren’s syndrome is a chronic systemic autoimmune disease affecting from 0.2 to 3% of the general population. The current treatment for Sjögren’s syndrome is aimed at controlling symptoms such as dry eyes and xerostomia. Systemic therapy with glucocorticoids or immunosuppressants is also used. [...] Read more.
Sjögren’s syndrome is a chronic systemic autoimmune disease affecting from 0.2 to 3% of the general population. The current treatment for Sjögren’s syndrome is aimed at controlling symptoms such as dry eyes and xerostomia. Systemic therapy with glucocorticoids or immunosuppressants is also used. Baricitinib is an immunosuppressant drug, specifically a Janus kinases 1 and 2 selective inhibitor. We propose ocular liposomal formulations loaded with baricitinib for the management of Sjögren’s syndrome. The novelty of the work relies on the fact that, for the first time, baricitinib is intended to be used for topical delivery. Two liposomal formulations were prepared with different lipids: (i) L-α-phosphatidylcholine (Lα-PC) and (ii) a combination of lipids 1-palmitoyl-2-oleoyl-phosphatidylethanolamine: s1-Palmitoyl-2-oleoyl-sn-glycerol-3-phosphoglycerol (3:1, mol/mol) (POPE:POPG), and they were physicochemically characterized. The in vitro drug release and the ex vivo permeation through corneal and scleral tissues were also assessed. Finally, the tolerance of the formulations on the ocular tissues was evaluated by the HET-CAM technique, as well as through the histological analysis of the cornea and sclera and the cornea transparency. Both liposomes resulted in small, spherical shapes, with suitable physicochemical properties for the ocular administration. Lα-PC led to higher flux, permeation, and retention in the sclera, whereas POPE:POPG led to higher flux and permeation in the cornea. The formulations showed no irritant effects on the chorioallantoic membrane. Additionally, the liposomes did not affect the cornea transparency when they were applied, and the histological analysis did not reveal any structural alteration. Full article
(This article belongs to the Special Issue Liposomes for Transmucosal Drug Delivery)
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16 pages, 4792 KiB  
Article
Development of a Mucoadhesive Vehicle Based on Lyophilized Liposomes for Drug Delivery through the Sublingual Mucosa
by María José De Jesús Valle, Aranzazu Zarzuelo Castañeda, Cristina Maderuelo, Alejandro Cencerrado Treviño, Jorge Loureiro, Paula Coutinho and Amparo Sánchez Navarro
Pharmaceutics 2022, 14(7), 1497; https://doi.org/10.3390/pharmaceutics14071497 - 19 Jul 2022
Cited by 2 | Viewed by 1753
Abstract
A pharmaceutical vehicle based on lyophilized liposomes is proposed for the buccal administration of drugs aimed at systemic delivery through the sublingual mucosa. Liposomes made of egg phosphatidylcholine and cholesterol (7/3 molar ratio) were prepared and lyophilized in the presence of different additive [...] Read more.
A pharmaceutical vehicle based on lyophilized liposomes is proposed for the buccal administration of drugs aimed at systemic delivery through the sublingual mucosa. Liposomes made of egg phosphatidylcholine and cholesterol (7/3 molar ratio) were prepared and lyophilized in the presence of different additive mixtures with mucoadhesive and taste-masking properties. Palatability was assayed on healthy volunteers. The lyophilization cycle was optimized, and the lyophilized product was compressed to obtain round and capsule-shaped tables that were evaluated in healthy volunteers. Tablets were also assayed regarding weight and thickness uniformities, swelling index and liposome release. The results proved that lyophilized liposomes in unidirectional round tablets have palatability, small size, comfortability and buccal retention adequate for sublingual administration. In contact with water fluids, the tablets swelled, and rehydrated liposomes were released at a slower rate than permeation efficiency determined using a biomimetic membrane. Permeability efficiency values of 0.72 ± 0.34 µg/cm2/min and 4.18 ± 0.95 µg/cm2/min were obtained for the liposomes with and without additives, respectively. Altogether, the results point to the vehicle proposed as a liposomal formulation suitable for systemic drug delivery through the sublingual mucosa. Full article
(This article belongs to the Special Issue Liposomes for Transmucosal Drug Delivery)
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25 pages, 4127 KiB  
Article
Novel Osmoprotective DOPC-DMPC Liposomes Loaded with Antihypertensive Drugs as Potential Strategy for Glaucoma Treatment
by Miriam Ana González-Cela-Casamayor, José Javier López-Cano, Irene Bravo-Osuna, Vanessa Andrés-Guerrero, Marta Vicario-de-la-Torre, Manuel Guzmán-Navarro, José Manuel Benítez-del-Castillo, Rocío Herrero-Vanrell and Irene Teresa Molina-Martínez
Pharmaceutics 2022, 14(7), 1405; https://doi.org/10.3390/pharmaceutics14071405 - 04 Jul 2022
Cited by 5 | Viewed by 2206
Abstract
Glaucoma is a group of chronic irreversible neuropathies that affect the retina and the optic nerve. It is considered one of the leading causes of blindness in the world. Although it can be due to various causes, the most important modifiable risk factor [...] Read more.
Glaucoma is a group of chronic irreversible neuropathies that affect the retina and the optic nerve. It is considered one of the leading causes of blindness in the world. Although it can be due to various causes, the most important modifiable risk factor is the elevated intraocular pressure (IOP). In this case, the treatment of choice consists of instilling antihypertensive formulations on the ocular surface. The chronicity of the pathology, together with the low bioavailability of the drugs that are applied on the ocular surface, make it necessary to instill the formulations very frequently, which is associated, in many cases, with the appearance of dry eye disease (DED). The objective of this work is the design of topical ocular formulations capable of treating glaucoma and, at the same time, preventing DED. For this, two liposome formulations, loaded with brimonidine or with travoprost, were Tadeveloped using synthetic phospholipids and enriched by the addition of compounds with osmoprotective activity. The proposed formulations not only presented physicochemical characteristics (size, pH, osmolarity, surface tension, and viscosity) and encapsulation efficiency values (EE% of 24.78% and ≥99.01% for brimonidine and travoprost, respectively) suitable for ocular surface administration, but also showed good tolerance in human corneal and conjunctival cell cultures, as well as an in vitro osmoprotective activity. The hypotensive effect of both liposomal formulations was evaluated in normotensive albino New Zealand rabbits, showing a faster and longer lasting reduction of intraocular pressure in comparison to the corresponding commercialized products used as control. According to these results, the hypotensive liposomal formulations combined with osmoprotective agents would result in a very promising platform for the treatment of glaucoma and the simultaneous protection of the ocular surface. Full article
(This article belongs to the Special Issue Liposomes for Transmucosal Drug Delivery)
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16 pages, 3813 KiB  
Article
Liposomal β-Sitosterol Suppresses Metastasis of CT26/luc Colon Carcinoma via Inhibition of MMP-9 and Evoke of Immune System
by Chao-Yu Shen, Chia-Fen Lee, Wei-Taur Chou, Jeng-Jong Hwang, Yeu-Sheng Tyan and Hui-Yen Chuang
Pharmaceutics 2022, 14(6), 1214; https://doi.org/10.3390/pharmaceutics14061214 - 07 Jun 2022
Cited by 8 | Viewed by 2161
Abstract
β-sitosterol (SITO) has been reported with anticancer effects; however, with poor bioavailability. The current study aimed to investigate whether liposomal encapsulated β-sitosterol (LS) has a better inhibition effect on tumor metastasis than β-sitosterol in a CT26/luc lung metastasis mouse model and the [...] Read more.
β-sitosterol (SITO) has been reported with anticancer effects; however, with poor bioavailability. The current study aimed to investigate whether liposomal encapsulated β-sitosterol (LS) has a better inhibition effect on tumor metastasis than β-sitosterol in a CT26/luc lung metastasis mouse model and the possible underlying mechanism. LS was liposomal-encapsulated SITO and was delivered to mice by oral gavage. The cell viability was determined by the MTT assay, and invasiveness of the tumor cells and related protein expression were evaluated with the invasion assay and Western blotting. For therapeutic efficacy evaluation, male BALB/c mice were treated with PBS, SITO, and LS once a day for 7 days prior to intravenous injections of CT26/luc cells; treatments were continued twice a week post-cell inoculation throughout the entire experiment. Tumor growth inhibition was monitored by bioluminescent imaging (BLI). IL-12, IL-18, and IFN-γ in the intestinal epithelium were determined by ELISA. The results show that LS treatment had a better invasion inhibition with lower cytotoxicity than SITO when the same dose was utilized. Notably, mice treated with LS significantly exhibited fewer metastases to the lungs and other tissues/organs compared with the Control and SITO groups. Additionally, the IL-12, IL-18, and IFN-γ levels were significantly increased in the LS-treated mice compared with the Control and SITO groups. The underlying mechanism may be through the inhibition of MMP-9 and elicitation of the antitumoral Th1 immune response, such as increasing CD4+ and CD8+ T cells, IL-12, IL-18, and IFN-γ. Full article
(This article belongs to the Special Issue Liposomes for Transmucosal Drug Delivery)
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26 pages, 9348 KiB  
Article
Novel Luteolin-Loaded Chitosan Decorated Nanoparticles for Brain-Targeting Delivery in a Sporadic Alzheimer’s Disease Mouse Model: Focus on Antioxidant, Anti-Inflammatory, and Amyloidogenic Pathways
by Haidy Abbas, Nesrine S El Sayed, Nancy Abdel Hamid Abou Youssef, Passent M. E. Gaafar, Mohamed R. Mousa, Ahmed M. Fayez and Manal A Elsheikh
Pharmaceutics 2022, 14(5), 1003; https://doi.org/10.3390/pharmaceutics14051003 - 06 May 2022
Cited by 26 | Viewed by 2745
Abstract
Preparation and evaluation of a non-invasive intranasal luteolin delivery for the management of cognitive dysfunction in Alzheimer’s disease (AD) using novel chitosan decorated nanoparticles. Development of luteolin-loaded chitosomes was followed by full in vitro characterization. In vivo efficacy was evaluated using a sporadic [...] Read more.
Preparation and evaluation of a non-invasive intranasal luteolin delivery for the management of cognitive dysfunction in Alzheimer’s disease (AD) using novel chitosan decorated nanoparticles. Development of luteolin-loaded chitosomes was followed by full in vitro characterization. In vivo efficacy was evaluated using a sporadic Alzheimer’s disease (SAD) animal model via intracerebroventricular injection of 3 mg/kg streptozotocin (ICV-STZ). Treatment groups of luteolin suspension and chitosomes (50 mg/kg) were then intranasally administered after 5 h of ICV-STZ followed by everyday administration for 21 consecutive days. Behavioral, histological, immunohistochemical, and biochemical studies were conducted. Chitosomes yielded promising quality attributes in terms of particle size (PS) (412.8 ± 3.28 nm), polydispersity index (PDI) (0.378 ± 0.07), Zeta potential (ZP) (37.4 ± 2.13 mv), and percentage entrapment efficiency (EE%) (86.6 ± 2.05%). Behavioral findings showed obvious improvement in the acquisition of short-term and long-term spatial memory. Furthermore, histological evaluation revealed an increased neuronal survival rate with a reduction in the number of amyloid plaques. Biochemical results showed improved antioxidant effects and reduced pro-inflammatory mediators’ levels. In addition, a suppression by half was observed in the levels of both Aβ aggregation and hyperphosphorylated-tau protein in comparison to the model control group which in turn confirmed the capability of luteolin-loaded chitosomes (LUT-CHS) in attenuating the pathological changes of AD. The prepared nanoparticles are considered a promising safe, effective, and non-invasive nanodelivery system that improves cognitive function in SAD albino mice as opposed to luteolin suspension. Full article
(This article belongs to the Special Issue Liposomes for Transmucosal Drug Delivery)
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