Submit to Pharmaceutics Review for Pharmaceutics Propose a Special Issue

Journal Browser

Overcoming Physiological Barriers Using Lipid Nanosystems

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

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

Deadline for manuscript submissions: closed (15 December 2021) | Viewed by 24290

Share This Special Issue

Special Issue Editors

Dr. Carla Martins Lopes

E-Mail Website
Guest Editor

1. FP-BHS—Biomedical and Health Sciences Research Unit, FP-I3ID—Instituto de Investigação, Inovação e Desenvolvimento, Faculty of Health Science, Fernando Pessoa University, 4200-150 Porto, Portugal
2. UCIBIO—Applied Molecular Biosciences Unit, MedTech—Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, 050-313 Porto, Portugal
Interests: bioactive delivery systems; lipid-based nanosystems; hybrid nanosystems; controlled delivery; multifunctional nanosystems
Special Issues, Collections and Topics in MDPI journals

Dr. Marlene Lucio

E-Mail Website
Guest Editor

1. CF-UM-UP, Centro de Física das Universidades do Minho e Porto, Departamento de Física da Universidade do Minho, 4710-057 Braga, Portugal
2. CBMA, Centro de Biologia Molecular e Ambiental, Departamento de Biologia, Universidade do Minho, 4710-057 Braga, Portugal
Interests: nanocarriers; nanotherapeutics; membrane model systems; ADMET profiling; biophysical techniques
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The delivery of therapeutics using nanocarrier systems is an interdisciplinary area of study that aims to allow for the administration of complex new medicines and add substantial value to medicines currently on the market. Among the many nanocarrier systems, lipid-based nanosystems such as liposomes, solid lipid nanoparticles, and nanostructured lipid carriers are recognized as promising commercial nanotherapeutic delivery systems due to their advantages of higher biocompatibility and lower toxicity. Currently, the production of nanomedicines consisting of lipid nanosystems that can supply therapeutic agents to a proper place at an appropriate time is an attractive field of research in pharmaceutical development. One of the main challenges to the development of nanomedicines is overcoming physiological barriers such as skin, mucosal membranes, the blood–brain barrier, and cell and nuclear membranes. Although these barriers play a normal protective role in the body, they hinder the delivery of therapeutic agents to the body. A variety of approaches have been developed to overcome these barriers, including the rational development of finely tuned formulations and targeting and triggering strategies, to address complex and challenging issues in the transport of therapeutic agents across several physiological barriers, including membranes, pH gradients, and enzymes, and their delivery to cellular and intracellular target sites.

This Special Issue seeks to present a collection of studies describing recent advances in the development of lipid nanosystems suited for the delivery of therapeutic agents and focused on overcoming physiological barriers.

Dr. Carla M. Lopes
Dr. Marlene Lucio
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

lipid nanosystems
physiological barriers
skin delivery
mucosal delivery
brain delivery
cell delivery
nuclear delivery

Published Papers (6 papers)

Download All Papers

Research

Jump to: Review

21 pages, 4634 KiB

Open AccessArticle

Formulation and Evaluation of SNEDDS Loaded with Original Lipophenol for the Oral Route to Prevent Dry AMD and Stragardt’s Disease

by Maxime Vincent, Laurianne Simon, Philippe Brabet, Philippe Legrand, Christophe Dorandeu, Josephine Lai Kee Him, Thierry Durand, Céline Crauste and Sylvie Begu

Pharmaceutics 2022, 14(5), 1029; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14051029 - 10 May 2022

Cited by 6 | Viewed by 3317

Abstract

Dry age-related macular degeneration (Dry AMD) and Stargardt’s disease (STGD1) are common eye diseases, characterized by oxidative and carbonyl stress (COS)-inducing photoreceptor degeneration and vision loss. Previous studies have demonstrated the protective effect of photoreceptors after the intravenous administration of a new lipophenol drug, phloroglucinol-isopropyl-DHA (IP-DHA). In this study, we developed an oral formulation of IP-DHA (BCS Class IV) relying on a self-nanoemulsifying drug delivery system (SNEDDS). SNEDDS, composed of Phosal^® 53 MCT, Labrasol^®, and Transcutol HP^® at a ratio of 25/60/15 (w/w/w), led to a homogeneous nanoemulsion (NE) with a mean size of 53.5 ± 4.5 nm. The loading of IP-DHA in SNEDDS (SNEDDS-IP-DHA) was successful, with a percentage of IP-DHA of 99.7% in nanoemulsions. The in vivo study of the therapeutic potency of SNEDDS-IP-DHA after oral administration on mice demonstrated photoreceptor protection after the induction of retinal degeneration with acute light stress (73–80%) or chronic light stress (52–69%). Thus, SNEDDS formulation proved to increase the solubility of IP-DHA, improving its stability in intestinal media and allowing its passage through the intestinal barrier after oral force-fed administration, while maintaining its biological activity. Therefore, SNEDDS-IP-DHA is a promising future preventive treatment for dry AMD and STGD1. Full article

(This article belongs to the Special Issue Overcoming Physiological Barriers Using Lipid Nanosystems)

► Show Figures

Figure 1

18 pages, 2540 KiB

Open AccessArticle

Formulation, Characterization, and Cytotoxicity Evaluation of Lactoferrin Functionalized Lipid Nanoparticles for Riluzole Delivery to the Brain

by Maria Inês Teixeira, Carla Martins Lopes, Hugo Gonçalves, José Catita, Ana Margarida Silva, Francisca Rodrigues, Maria Helena Amaral and Paulo C. Costa

Pharmaceutics 2022, 14(1), 185; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14010185 - 13 Jan 2022

Cited by 26 | Viewed by 4494

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a very poor prognosis. Its treatment is hindered by a lack of new therapeutic alternatives and the existence of the blood–brain barrier (BBB), which restricts the access of drugs commonly used in ALS, such as riluzole, to the brain. To overcome these limitations and increase brain targeting, riluzole-loaded nanostructured lipid carriers (NLC) were prepared and functionalized with lactoferrin (Lf), facilitating transport across the BBB by interacting with Lf receptors expressed in the brain endothelium. NLC were characterized with respect to their physicochemical properties (size, zeta potential, polydispersity index) as well as their stability, encapsulation efficiency, morphology, in vitro release profile, and biocompatibility. Moreover, crystallinity and melting behavior were assessed by DSC and PXRD. Nanoparticles exhibited initial mean diameters between 180 and 220 nm and a polydispersity index below 0.3, indicating a narrow size distribution. NLC remained stable over at least 3 months. Riluzole encapsulation efficiency was very high, around 94–98%. FTIR and protein quantification studies confirmed the conjugation of Lf on the surface of the nanocarriers, with TEM images showing that the functionalized NLC presented a smooth surface and uniform spherical shape. An MTT assay revealed that the nanocarriers developed in this study did not cause a substantial reduction in the viability of NSC-34 and hCMEC/D3 cells at a riluzole concentration up to 10 μM, being therefore biocompatible. The results suggest that Lf-functionalized NLC are a suitable and promising delivery system to target riluzole to the brain. Full article

(This article belongs to the Special Issue Overcoming Physiological Barriers Using Lipid Nanosystems)

► Show Figures

Graphical abstract

22 pages, 16568 KiB

Open AccessArticle

Omega-3- and Resveratrol-Loaded Lipid Nanosystems for Potential Use as Topical Formulations in Autoimmune, Inflammatory, and Cancerous Skin Diseases

by Ana R. Caldas, José Catita, Raul Machado, Artur Ribeiro, Fátima Cerqueira, Bruno Horta, Rui Medeiros, Marlene Lúcio and Carla M. Lopes

Pharmaceutics 2021, 13(8), 1202; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13081202 - 04 Aug 2021

Cited by 15 | Viewed by 3120

Abstract

Resveratrol (RSV) and omega 3 (ω₃), because of their biological favorable properties, have become subjects of interest for researchers in dermocosmetic and pharmaceutical industries; however, these bioactives present technological limitations that hinder their effective delivery to the target skin layer. To overcome the stability and skin permeation limitations of free bioactives, this work proposes a combined strategy involving two different lipid nanosystems (liposomes and lipid nanoparticles) that include ω₃ in their lipid matrix. Additionaly, RSV is only encapsulated in liposomes that provid an adequate amphiphilic environment. Each formulation is thoroughly characterized regarding their physical–chemical properties. Subsequently, the therapeutic performance of the lipid nanosystems is evaluated based on their protective roles against lipid peroxidation, as well as inhibition of cicloxygenase (COX) and nitric oxid (NO) production in the RWA264.7 cell line. Finally, the lipid nanosystems are incorporated in hydrogel to allow their topical administration, then rheology, occlusion, and RSV release–diffusion assays are performed. Lipid nanoparticles provide occlusive effects at the skin surface. Liposomes provide sustained RSV release and their flexibility conferred by edge activator components enhances RSV diffusion, which is required to reach NO production cells and COX cell membrane enzymes. Overall, the inclusion of both lipid nanosystems in the same semisolid base constitutes a promising strategy for autoimmune, inflammatory, and cancerous skin diseases. Full article

(This article belongs to the Special Issue Overcoming Physiological Barriers Using Lipid Nanosystems)

► Show Figures

Figure 1

17 pages, 2386 KiB

Open AccessArticle

Safety and Tolerability of Topical Ophthalmic Triamcinolone Acetonide-Loaded Liposomes Formulation and Evaluation of Its Biologic Activity in Patients with Diabetic Macular Edema

by Jose Navarro-Partida, Juan Carlos Altamirano-Vallejo, Alejandro Gonzalez-De la Rosa, Juan Armendariz-Borunda, Carlos Rodrigo Castro-Castaneda and Arturo Santos

Pharmaceutics 2021, 13(3), 322; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13030322 - 02 Mar 2021

Cited by 14 | Viewed by 2254

Abstract

Intravitreal injections (IVTs) of corticosteroids as triamcinolone acetonide (TA) are frequently used for the treatment of many vitreous and retinal disorders. However, IVTs are related to severe ocular complications. Lately, a topical ophthalmic TA-loaded liposomes formulation (TALF) was designed to transport TA into the posterior segment of the eye when instilled on the ocular surface. To evaluate the safety, tolerability, and biological activity of TALF, an animal study and a phase I clinical assay were performed. Moreover, four patients with diabetic macular edema (DME) were treated with TALF in order to explore the biological activity of the formulation. No inflammation, lens opacity, swelling, or increase in intraocular pressure were recorded after the instillation of TALF in any of the animal or clinical studies. Mainly, mild and transient adverse events such as dry eye and burning were reported. TALF significantly improves visual acuity and diminishes central foveal thickness in patients with DME. The current data demonstrate the safety, tolerability, and biological activity of TALF. It seems that TALF can be used topically to treat vitreous and retinal diseases that respond to TA such as DME, avoiding the use of corticosteroid IVTs and their associated hazards. Full article

(This article belongs to the Special Issue Overcoming Physiological Barriers Using Lipid Nanosystems)

► Show Figures

Figure 1

Review

Jump to: Research

24 pages, 1912 KiB

Open AccessReview

Nanoparticulate Drug Delivery Strategies to Address Intestinal Cytochrome P450 CYP3A4 Metabolism towards Personalized Medicine

by Rui Xue Zhang, Ken Dong, Zhigao Wang, Ruimin Miao, Weijia Lu and Xiao Yu Wu

Pharmaceutics 2021, 13(8), 1261; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13081261 - 16 Aug 2021

Cited by 18 | Viewed by 5982

Abstract

Drug dosing in clinical practice, which determines optimal efficacy, toxicity or ineffectiveness, is critical to patients’ outcomes. However, many orally administered therapeutic drugs are susceptible to biotransformation by a group of important oxidative enzymes, known as cytochrome P450s (CYPs). In particular, CYP3A4 is a low specificity isoenzyme of the CYPs family, which contributes to the metabolism of approximately 50% of all marketed drugs. Induction or inhibition of CYP3A4 activity results in the varied oral bioavailability and unwanted drug-drug, drug-food, and drug-herb interactions. This review explores the need for addressing intestinal CYP3A4 metabolism and investigates the opportunities to incorporate lipid-based oral drug delivery to enable precise dosing. A variety of lipid- and lipid-polymer hybrid-nanoparticles are highlighted to improve drug bioavailability. These drug carriers are designed to target different intestinal regions, including (1) local saturation or inhibition of CYP3A4 activity at duodenum and proximal jejunum; (2) CYP3A4 bypass via lymphatic absorption; (3) pH-responsive drug release or vitamin-B₁₂ targeted cellular uptake in the distal intestine. Exploitation of lipidic nanosystems not only revives drugs removed from clinical practice due to serious drug-drug interactions, but also provide alternative approaches to reduce pharmacokinetic variability. Full article

(This article belongs to the Special Issue Overcoming Physiological Barriers Using Lipid Nanosystems)

► Show Figures

Graphical abstract

25 pages, 3399 KiB

Open AccessReview

Lipid-Based Nanocarriers as Topical Drug Delivery Systems for Intraocular Diseases

by Jose Navarro-Partida, Carlos Rodrigo Castro-Castaneda, Francisco J. Santa Cruz-Pavlovich, Luis Abraham Aceves-Franco, Tomer Ori Guy and Arturo Santos

Pharmaceutics 2021, 13(5), 678; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13050678 - 09 May 2021

Cited by 23 | Viewed by 3930

Abstract

Effective drug delivery to intraocular tissues remains a great challenge due to complex anatomical and physiological barriers that selectively limit the entry of drugs into the eye. To overcome these challenges, frequent topical application and regular intravitreal injections are currently used to achieve the desired drug concentrations into the eye. However, the repetitive installation or recurrent injections may result in several side effects. Recent advancements in the field of nanoparticle-based drug delivery have demonstrated promising results for topical ophthalmic nanotherapies in the treatment of intraocular diseases. Studies have revealed that nanocarriers enhance the intraocular half-life and bioavailability of several therapies including proteins, peptides and genetic material. Amongst the array of nanoparticles available nowadays, lipid-based nanosystems have shown an increased efficiency and feasibility in topical formulations, making them an important target for constant and thorough research in both preclinical and clinical practice. In this review, we will cover the promising lipid-based nanocarriers used in topical ophthalmic formulations for intraocular drug delivery. Full article

(This article belongs to the Special Issue Overcoming Physiological Barriers Using Lipid Nanosystems)

► Show Figures