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Pharmaceutical Formulation of Marine Drugs

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A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 27921

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Prof. Dr. Alexander N. Shikov

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Department of Technology of Pharmaceutical Formulations, Saint-Petersburg State Chemical Pharmaceutical University, Saint-Petersburg, Russia
Interests: natural products; sea urchins; algae; chemistry; pharmacology
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Special Issue Information

Dear Colleagues,

Marine organisms represent an excellent source of innovative compounds, having tremendous potential for the development of new drugs. Intensive exploring of marine organisms led to isolation and identification of thousands of new potent individual compounds. Marine derived compounds (MDC) are exceptionally interesting high-value ingredients for applications in the pharmaceutical industry. However, just a few marine-derived drugs are available in the global market. MDC have been used in pharmaceutical formulations as drug carriers, for coating, film formation, as matrix materials for targeted drug delivery, as a transporter for improving the drugs bioavailability etc.

For this special issue we invite the scientists who work in the development of pharmaceutical formulations from MDC to contribute with research articles, mini reviews and reviews.

Prof. Dr. Alexander N. Shikov
Guest Editor

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. Marine Drugs 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

aerosols
bioavailability
capsules
controlled release
cosmetic formulations
dissolution test
formulations for injection
ointment
ophthalmological formulations
oral dispersible systems
penetration
pharmaceutical excipients
pharmacokinetic
photoprotective
solid dosage forms
sunscreen
transdermal formulations
transdermal therapeutic systems
solutions
tablets
cream
extracts
films
gel

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Published Papers (9 papers)

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Research

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14 pages, 2739 KiB

Open AccessArticle

Chitosan-Based Films with 2-Aminothiophene Derivative: Formulation, Characterization and Potential Antifungal Activity

by Verônica da Silva Oliveira, Meriângela Miranda da Cruz, Gabriela Suassuna Bezerra, Natan Emanuell Sobral e Silva, Fernando Henrique Andrade Nogueira, Guilherme Maranhão Chaves, José Lamartine Soares Sobrinho, Francisco Jaime Bezerra Mendonça-Junior, Bolívar Ponciano Goulart de Lima Damasceno, Attilio Converti and Ádley Antonini Neves de Lima

Mar. Drugs 2022, 20(2), 103; https://doi.org/10.3390/md20020103 - 26 Jan 2022

Cited by 10 | Viewed by 2667

Abstract

In this study, films of chitosan and 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN), a 2-aminothiophene derivative with great pharmacological potential, were prepared as a system for a topical formulation. 6CN-chitosan films were characterized by physicochemical analyses, such as Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and scanning electronic microscopy (SEM). Additionally, the antifungal potential of the films was evaluated in vitro against three species of Candida (C. albicans, C. tropicalis, and C. parapsilosis). The results of the FTIR and thermal analysis showed the incorporation of 6CN in the polymer matrix. In the diffractogram, the 6CN-chitosan films exhibited diffraction halos that were characteristic of amorphous structures, while the micrographs showed that 6CN particles were dispersed in the chitosan matrix, exhibiting pores and cracks on the film surface. In addition, the results of antifungal investigation demonstrated that 6CN-chitosan films were effective against Candida species showing potential for application as a new antifungal drug. Full article

(This article belongs to the Special Issue Pharmaceutical Formulation of Marine Drugs)

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17 pages, 2955 KiB

Open AccessArticle

Development of Immediate Release Tablets Containing Calcium Lactate Synthetized from Black Sea Mussel Shells

by Magdalena Mititelu, Elena Moroșan, Anca Cecilia Nicoară, Ana Andreea Secăreanu, Adina Magdalena Musuc, Irina Atkinson, Jeanina Pandele Cusu, George Mihai Nițulescu, Emma Adriana Ozon, Iulian Sarbu and Teodora Dalila Balaci

Mar. Drugs 2022, 20(1), 45; https://doi.org/10.3390/md20010045 - 2 Jan 2022

Cited by 21 | Viewed by 3618

Abstract

Nowadays, the use of marine by-products as precursor materials has gained great interest in the extraction and production of chemical compounds with suitable properties and possible pharmaceutical applications. The present paper presents the development of a new immediate release tablet containing calcium lactate obtained from Black Sea mussel shells. Compared with other calcium salts, calcium lactate has good solubility and bioavailability. In the pharmaceutical preparations, calcium lactate was extensively utilized as a calcium source for preventing and treating calcium deficiencies. The physical and chemical characteristics of synthesized calcium lactate were evaluated using Fourier Transform Infrared Spectroscopy, X-ray diffraction analysis and thermal analysis. Further, the various pharmacotechnical properties of the calcium lactate obtained from mussel shells were determined in comparison with an industrial used direct compressible Calcium lactate DC (PURACAL^®). The obtained results suggest that mussel shell by-products are suitable for the development of chemical compounds with potential applications in the pharmaceutical domain. Full article

(This article belongs to the Special Issue Pharmaceutical Formulation of Marine Drugs)

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24 pages, 5428 KiB

Open AccessArticle

Cliona varians-Derived Actinomycetes as Bioresources of Photoprotection-Related Bioactive End-Products

by Jeysson Sánchez-Suárez, Luisa Villamil, Ericsson Coy-Barrera and Luis Díaz

Mar. Drugs 2021, 19(12), 674; https://doi.org/10.3390/md19120674 - 27 Nov 2021

Cited by 4 | Viewed by 3578

Abstract

Sunscreen and sunblock are crucial skincare products to prevent photoaging and photocarcinogenesis through the addition of chemical filters to absorb or block ultraviolet (UV) radiation. However, several sunscreen and sunblock ingredients, mostly UV filters, have been associated with human and environmental safety concerns. Therefore, the exploration and discovery of promising novel sources of efficient and safer compounds with photoprotection-related activities are currently required. Marine invertebrates, particularly their associated microbiota, are promising providers of specialized metabolites with valuable biotechnological applications. Nevertheless, despite Actinobacteria members being a well-known source of bioactive metabolites, their photoprotective potential has been poorly explored so far. Hence, a set of methanolic extracts obtained from Cliona varians-derived actinomycetes was screened regarding their antioxidant and UV-absorbing capacities (i.e., photoprotection-related activities). The active extract-producing strains were identified and classified within genera Streptomyces, Micrococcus, Gordonia, and Promicromonospora. This is the first report of the isolation of these microorganisms from C. varians (an ecologically important Caribbean coral reef-boring sponge). The in vitro cytotoxicity on dermal fibroblasts of oxybenzone and the selected active extracts revealed that oxybenzone exerted a cytotoxic effect, whereas no cytotoxic effect of test extracts was observed. Accordingly, the most active (SPFi > 5, radical scavenging > 50%) and nontoxic (cell viability > 75%) extracts were obtained from Streptomyces strains. Finally, LC-MS-based characterization suggested a broad chemical space within the test strains and agreed with the reported streptomycetes’ chemodiversity. The respective metabolite profiling exposed a strain-specific metabolite occurrence, leading to the recognition of potential hits. These findings suggest that marine Streptomyces produce photoprotectants ought to be further explored in skincare applications. Full article

(This article belongs to the Special Issue Pharmaceutical Formulation of Marine Drugs)

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14 pages, 1149 KiB

Open AccessArticle

Formulation, Optimization and In Vivo Evaluation of Fucoidan-Based Cream with Anti-Inflammatory Properties

by Ekaterina D. Obluchinskaya, Olga N. Pozharitskaya, Elena V. Flisyuk and Alexander N. Shikov

Mar. Drugs 2021, 19(11), 643; https://doi.org/10.3390/md19110643 - 17 Nov 2021

Cited by 31 | Viewed by 4173

Abstract

Fucoidan is a polysaccharide found in brown alga with glorious potential for pharmacological activities, among which its anti-inflammatory properties have gained meaningful attention. Due to several advantages of formulations for topical application, this study aimed to develop and optimize a fucoidan-based cream formulation and to investigate its anti-inflammatory potential after topical application in vivo. Fucoidan from Fucus vesiculosus L. was used. The cream base consisting of olive oil and Kolliphor RH40 was optimized followed by in vitro agar diffusion and drug release studies. The fucoidan-based cream with 13% Kolliphor P 407, 1% Transcutol P, and 5% PEG400 showed good spreadability, washability, and colloidal stability, and it did not irritate the skin. The kinetics of fucoidan release from the optimized cream exhibited the best fit to the Korsmeyer–Peppas and Higuchi models with R² > 0.99. Fucoidan release was controlled by drug diffusion and anomalous transport provided by the optimized cream base. The formulation was stable and provided high fucoidan release after storage for 1 year. Topical application of the fucoidan-based cream dose-dependently inhibited carrageenan-induced edema and ameliorated mechanical allodynia in rats. The efficacy of the fucoidan-based cream at a high dose was comparable with the efficacy of diclofenac gel. The fucoidan-based cream could be considered a promising anti-inflammatory formulation. Full article

(This article belongs to the Special Issue Pharmaceutical Formulation of Marine Drugs)

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15 pages, 2196 KiB

Open AccessArticle

Loading Effect of Chitosan Derivative Nanoparticles on Different Antigens and Their Immunomodulatory Activity on Dendritic Cells

by Chaojie Xu, Ronge Xing, Song Liu, Yukun Qin, Kecheng Li, Huahua Yu and Pengcheng Li

Mar. Drugs 2021, 19(10), 536; https://doi.org/10.3390/md19100536 - 24 Sep 2021

Viewed by 2036

Abstract

Drug carrier nanoparticles (NPs) were prepared by the polyelectrolyte method, with chitosan sulfate, with different substituents and quaternary ammonium chitosan, including C236-HACC NPs, C36-HACC NPs, and C6-HACC NPs. To evaluate whether the NPs are suitable for loading different antigens, we chose bovine serum albumin (BSA), ovalbumin (OVA), and myoglobin (Mb) as model antigens to investigate the encapsulation effect of the NPs. The characteristics (size, potential, and encapsulation efficiency) of the NPs were measured. Moreover, the NPs with higher encapsulation efficiency were selected for the immunological activity research. The results showed that chitosan derivative NPs with different substitution sites had different loading effects on the three antigens, and the encapsulation rate of BSA and OVA was significantly better than that of Mb. Moreover, the NPs encapsulated with different antigens have different immune stimulating abilities to DCS cells, the immune effect of OVA-coated NPs was significantly better than that of BSA-coated NPs and blank NPs, especially C236-HACC-OVA NPs. Furthermore, we found that C236-HACC-OVA NPs could increase the phosphorylation level of intracellular proteins to activate cell pathways. Therefore, C236-HACC NPs are more suitable for the loading of antigens similar to the OVA structure. Full article

(This article belongs to the Special Issue Pharmaceutical Formulation of Marine Drugs)

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16 pages, 4582 KiB

Open AccessArticle

Spray Drying of Chitosan Acid Salts: Process Development, Scaling Up and Physicochemical Material Characterization

by Nilia de la Paz, Mirna Fernández, Orestes López, Caridad Garcia, Antonio Nogueira, Leonid Torres, Wilfredo Turiño and Jyrki Heinämäki

Mar. Drugs 2021, 19(6), 329; https://doi.org/10.3390/md19060329 - 6 Jun 2021

Cited by 2 | Viewed by 2836

Abstract

We investigated a spray drying process for preparing water-soluble salts of high molecular weight chitosan (CH) intended for pharmaceutical excipient applications. CH was derived from chitin of marine lobster origin (Panulirus argus). The effects of organic acid (acetic or lactic acid) and the ratio (difference) of inlet/outlet air temperature (140/90 °C or 160/100 °C) on spray drying were studied. The yield of spray-dried CH salt powders ranged from 50% to 99% in laboratory and industrial-scale processes. The spray-dried dry powder of CH salts consisted of spherical agglomerated particles with an average diameter of 36.2 ± 7.0 µm (CH acetate) and 108.6 ± 11.5 µm (CH lactate). After dispersing the spray-dried CH salt powder samples in purified water, the mean particle sizes obtained for the CH acetate salts were 31.4 nm (batch A001), 33.0 nm (A002) and 44.2 nm (A003), and for the CH lactate salts 100.8 nm (batch L001), 103.2 nm (L002) and 121.8 nm (L003). The optimum process conditions for spray drying were found: an inlet air temperature of 160 ± 5 °C, an outlet temperature of 100 ± 5 °C and an atomizer disk rotational speed of 18,200 min⁻¹. The X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) results confirmed the amorphous state of the CH salts. The ¹H nuclear magnetic resonance (NMR) and Fourier transform infrared (FT-IR) spectra of CH acetate and lactate salts verified that the spray drying process does not affect the polymer backbone. In conclusion, both laboratory and industrial-scale spray drying methods for preparing water-soluble acid salts of CH are reproducible, and the physicochemical properties of the corresponding CH acid salts are uniform. Full article

(This article belongs to the Special Issue Pharmaceutical Formulation of Marine Drugs)

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13 pages, 1230 KiB

Open AccessArticle

Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from Holothuria fuscopunctata, a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods

by Shuang Liu, Taocui Zhang, Huifang Sun, Lisha Lin, Na Gao, Weili Wang, Sujuan Li and Jinhua Zhao

Mar. Drugs 2021, 19(4), 212; https://doi.org/10.3390/md19040212 - 11 Apr 2021

Cited by 4 | Viewed by 2825

Abstract

dHG-5 (Mw 5.3 kD) is a depolymerized glycosaminoglycan from sea cucumber Holothuria fuscopunctata. As a selective inhibitor of intrinsic Xase (iXase), preclinical study showed it was a promising anticoagulant candidate without obvious bleeding risk. In this work, two bioanalytical methods based on the anti-iXase and activated partial thromboplastin time (APTT) prolongation activities were established and validated to determine dHG-5 concentrations in plasma and urine samples. After single subcutaneous administration of dHG-5 at 5, 9, and 16.2 mg/kg to rats, the time to peak concentration (T_max) was at about 1 h, and the peak concentration (C_max) was 2.70, 6.50, and 10.11 μg/mL, respectively. The plasma elimination half-life(T_1/2_β) was also about 1 h and dHG-5 could be almost completely absorbed after s.c. administration. Additionally, the pharmacodynamics of dHG-5 was positively correlated with its pharmacokinetics, as determined by rat plasma APTT and anti-iXase method, respectively. dHG-5 was mainly excreted by urine as the unchanged parent drug and about 60% was excreted within 48 h. The results suggested that dHG-5 could be almost completely absorbed after subcutaneous injection and the pharmacokinetics of dHG-5 are predictable. Studying pharmacokinetics of dHG-5 could provide valuable information for future clinical studies. Full article

(This article belongs to the Special Issue Pharmaceutical Formulation of Marine Drugs)

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Review

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42 pages, 2499 KiB

Open AccessReview

Multiple Roles of Chitosan in Mucosal Drug Delivery: An Updated Review

by Paola Mura, Francesca Maestrelli, Marzia Cirri and Natascia Mennini

Mar. Drugs 2022, 20(5), 335; https://doi.org/10.3390/md20050335 - 20 May 2022

Cited by 62 | Viewed by 7180

Abstract

Chitosan (CS) is a linear polysaccharide obtained by the deacetylation of chitin, which, after cellulose, is the second biopolymer most abundant in nature, being the primary component of the exoskeleton of crustaceans and insects. Since joining the pharmaceutical field, in the early 1990s, CS attracted great interest, which has constantly increased over the years, due to its several beneficial and favorable features, including large availability, biocompatibility, biodegradability, non-toxicity, simplicity of chemical modifications, mucoadhesion and permeation enhancer power, joined to its capability of forming films, hydrogels and micro- and nanoparticles. Moreover, its cationic character, which renders it unique among biodegradable polymers, is responsible for the ability of CS to strongly interact with different types of molecules and for its intrinsic antimicrobial, anti-inflammatory and hemostatic activities. However, its pH-dependent solubility and susceptibility to ions presence may represent serious drawbacks and require suitable strategies to be overcome. Presently, CS and its derivatives are widely investigated for a great variety of pharmaceutical applications, particularly in drug delivery. Among the alternative routes to overcome the problems related to the classic oral drug administration, the mucosal route is becoming the favorite non-invasive delivery pathway. This review aims to provide an updated overview of the applications of CS and its derivatives in novel formulations intended for different methods of mucosal drug delivery. Full article

(This article belongs to the Special Issue Pharmaceutical Formulation of Marine Drugs)

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32 pages, 2267 KiB

Open AccessFeature PaperReview

An Overview of Potential Seaweed-Derived Bioactive Compounds for Pharmaceutical Applications

by Silvia Lomartire and Ana M. M. Gonçalves

Mar. Drugs 2022, 20(2), 141; https://doi.org/10.3390/md20020141 - 15 Feb 2022

Cited by 100 | Viewed by 12702

Abstract

Nowadays, seaweeds are widely involved in biotechnological applications. Due to the variety of bioactive compounds in their composition, species of phylum Ochrophyta, class Phaeophyceae, phylum Rhodophyta and Chlorophyta are valuable for the food, cosmetic, pharmaceutical and nutraceutical industries. Seaweeds have been consumed as whole food since ancient times and used to treat several diseases, even though the mechanisms of action were unknown. During the last decades, research has demonstrated that those unique compounds express beneficial properties for human health. Each compound has peculiar properties (e.g., antioxidant, antimicrobial, antiviral activities, etc.) that can be exploited to enhance human health. Seaweed’s extracted polysaccharides are already involved in the pharmaceutical industry, with the aim of replacing synthetic compounds with components of natural origin. This review aims at a better understanding of the recent uses of algae in drug development, with the scope of replacing synthetic compounds and the multiple biotechnological applications that make up seaweed’s potential in industrial companies. Further research is needed to better understand the mechanisms of action of seaweed’s compounds and to embrace the use of seaweeds in pharmaceutical companies and other applications, with the final scope being to produce sustainable and healthier products. Full article

(This article belongs to the Special Issue Pharmaceutical Formulation of Marine Drugs)

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