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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Physical Pharmacy and Formulation".

Deadline for manuscript submissions: closed (15 August 2024) | Viewed by 18512

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Dr. Ana Žugić

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Department of Pharmaceutical Technology and Development, Institute for Medicinal Plant Research "Dr. Josif Pancic", Belgrade, Serbia
Interests: phytopreparations; skin semi-solids; emulsions; nanoparticles; microparticles; biocompatible excipients; medicinal plants; phytochemistry
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Dr. Vanja Tadić

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Department of Pharmaceutical Technology and Development, Institute for Medicinal Plant Research "Dr. Josif Pancic", Belgrade, Serbia
Interests: natural compounds; pharmacognosy; biological activity of components originated from plants; standardization of phytopharmaceuticals; development of delivery systems for topical application
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Prof. Dr. Ivana Nešić

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Department of Pharmacy, Faculty of Medicine, University of Nis, Nis, Serbia
Interests: pharmaceutical development and herbal drug characterization; development of dermocosmetic products; microencapsulation; nanoencapsulation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to invite you to submit your manuscript(s) to the journal Pharmaceutics for a Special Issue entitled “Advances in Natural Products for Cutaneous Application” with open access. Traditional usage of natural products for cutaneous application stretches back millennia. In recent years, there has been a growing consumer demand for natural products on the market both as cosmetic products and for the local treatment of different skin impairments. Therefore, the active ingredients of these products include natural bioactive compounds (NBCs), either as isolated substances or as mixtures in herbal preparations, such as extracts, fatty oils, essential oils, expressed juices, and processed exudates. In parallel, there is an evident increase in scientific interest in natural products for cutaneous application. The development of these products represents a research challenge, which is related to several of their specificities. Namely, aside from safety and efficacy demands, specific quality requirements should be satisfied if the active ingredient of the product for the treatment of skin disorders is herbal preparation. This is due to their compounded chemical composition, where, among other tests, identification and quantification of appropriate substances and their stability should be assessed. In addition, when the products are intended for application on the skin, aesthetical acceptability for users after usage is of great importance, and thus special attention should be paid to their satisfactory sensory characteristics. Finally, unfavorable physicochemical properties of certain natural compounds and/or herbal preparations may require specific formulation strategies aimed at improving their solubility/bioavailability.

With this Special Issue, we would like to provide readers with the latest trends in the development of natural products for dermal application with actives being NBCs, intended for the care of normal or treatment of impaired skin. Therefore, we are interested in articles related to the evaluation of such products in terms of physicochemical and/or biopharmaceutical characterization, stability, efficacy, and safety assessment, as well as investigations of their sensory (aesthetic and applicative) properties.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

Topical Delivery Systems;
Nanoparticles and Nanotechnology;
Pharmaceutical Technology and Manufacturing;
Cosmetic products;
Dermal products.

Thank you for your time and consideration in this matter. We look forward to receiving your contributions.

Dr. Ana Žugić
Dr. Vanja Tadić
Prof. Dr. Ivana Nešić
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

natural bioactive compounds (NBCs)
herbal preparations
cosmeceuticals
systems for topical delivery
testing of skin performance
physico-chemical characterization/stability
analysis of texture
formulation development
release and permeation testing

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Published Papers (10 papers)

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Research

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18 pages, 5860 KiB

Open AccessArticle

Immortelle Essential-Oil-Enriched Hydrogel for Diabetic Wound Repair: Development, Characterization, and In Vivo Efficacy Assessment

by Marijana Andjic, Jovana Bradic, Aleksandar Kocovic, Marko Simic, Veljko Krstonosic, Ivan Capo, Vladimir Jakovljevic and Nevena Lazarevic

Pharmaceutics 2024, 16(10), 1309; https://doi.org/10.3390/pharmaceutics16101309 - 8 Oct 2024

Cited by 1 | Viewed by 1191

Abstract

Background: Alarming data revealed that 19% to 34% of adults with diabetes mellitus develop chronic wounds, which are characterized by impaired healing and a higher risk of infections. Inspired by the traditional use of immortelle for wound healing and the lack of scientific evidence regarding how it thoroughly influences tissue regeneration, we aimed to formulate a hydrogel loaded with immortelle essential oil and assess its effectiveness on diabetic excision wounds. Methods: The rheological properties of the hydrogel, an in vivo safety test, as well as wound healing capacity, were determined in rats with induced diabetes and excision wounds. Diabetic rats were divided into four groups: untreated, treated with 1% silver sulfadiazine ointment, treated with a gel base, and treated with the immortelle essential oil-based hydrogel. Results: It was revealed that the hydrogel exerts pseudoplastic behavior and has no potential to act as an irritant, thus highlighting its suitability for skin application. Moreover, analysis of macroscopic, biochemical, and histopathological data revealed that the immortelle essential oil-based hydrogel significantly improves wound repair. Superior re-epithelialization, scar maturation, and increased collagen fiber density were achieved after immortelle essential oil-based gel application. Conclusions: These findings suggest that the immortelle essential oil-based hydrogel could be a natural, safe, and effective wound-healing dressing. Full article

(This article belongs to the Special Issue Advances in Natural Products for Cutaneous Application)

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13 pages, 2078 KiB

Open AccessArticle

Assessment of Enzymatically Derived Blackcurrant Extract as Cosmetic Ingredient—Antioxidant Properties Determination and In Vitro Diffusion Study

by Anja Petrov Ivanković, Marija Ćorović, Ana Milivojević, Stevan Blagojević, Aleksandra Radulović, Rada Pjanović and Dejan Bezbradica

Pharmaceutics 2024, 16(9), 1209; https://doi.org/10.3390/pharmaceutics16091209 - 14 Sep 2024

Cited by 1 | Viewed by 1021

Abstract

Blackcurrant is an anthocyanin-rich berry with proven antioxidant and photoprotective activity and emerging prebiotic potential, widely applied in cosmetic products. Hereby, highly efficient enzyme-assisted extraction of blackcurrant polyphenols was performed, giving extract with very high antioxidant activity. Obtained extract was characterized in terms of anthocyanin composition, incorporated into three different cosmetic formulations and subjected to Franz cell diffusion study. Experimental values obtained using cellulose acetate membrane for all four dominant anthocyanins (delphinidin 3-glucoside, delphinidin 3-rutinoside, cyanidin 3-glucoside and cyanidin 3-rutinoside) were successfully fitted with the Korsmeyer–Peppas diffusion model. Calculated effective diffusion coefficients were higher for hydrogel compared to oil-in-water cream gel and oil-in-water emulsion, whereas the highest value was determined for cyanidin 3-rutinoside. On the other hand, after a 72 h long experiment with transdermal skin diffusion model (Strat-M^® membrane), no anthocyanins were detected in the receptor fluid, and only 0.5% of the initial quantity from the donor compartment was extracted from the membrane itself after experiment with hydrogel. Present study revealed that hydrogel is a suitable carrier system for the topical delivery of blackcurrant anthocyanins, while dermal and transdermal delivery of these molecules is very limited, which implies its applicability for treatments targeting skin surface (i.e., prebiotic, photoprotective). Full article

(This article belongs to the Special Issue Advances in Natural Products for Cutaneous Application)

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25 pages, 4120 KiB

Open AccessArticle

Extracts from Wheat, Maize, and Sunflower Waste as Natural Raw Materials for Cosmetics: Value-Added Products Reaching Sustainability Goals

by Milica Lukić, Ana Ćirić, Dragana D. Božić, Jelena Antić Stanković, Đorđe Medarević and Zoran Maksimović

Pharmaceutics 2024, 16(9), 1182; https://doi.org/10.3390/pharmaceutics16091182 - 7 Sep 2024

Viewed by 1126

Abstract

Agricultural waste is underutilized, and sometimes burning them has a negative impact on the environment and human health. This research investigates the untapped potential of extracts from maize, wheat and sunflower waste as natural materials for cutaneous, specifically, cosmetic application. The possibility of incorporating lipid and ethanol extracts from wheat, maize, and sunflower into creams was investigated together with their potential contribution to the structural and functional properties of the topical formulations. Results of the physicochemical characterization show that investigated extracts can be successfully incorporated into creams with satisfactory stability. All extracts showed a desirable safety profile and good antimicrobial activity against various microorganisms. Lipid extracts have proven to be promising structural ingredients of the oil phase, contributing to the spreadability, occlusivity, and emollient effect. Ethanol extracts influenced washability and stickiness of the formulation and could be considered as prospective ingredients in self-preserving formulations. The extracts affected the sensory properties of the creams, mainly the smell and color. These results suggest that the extracts from wheat, maize, and sunflower waste could be used as multifunctional natural ingredients for cosmetic formulations which can replace less sustainable raw materials. This also represents a valorization of waste and is in line with broader sustainability goals. Full article

(This article belongs to the Special Issue Advances in Natural Products for Cutaneous Application)

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16 pages, 2317 KiB

Open AccessArticle

Liposomal Encapsulation of Ascorbyl Palmitate: Influence on Skin Performance

by Aleksandra Stolić Jovanović, Vanja M. Tadić, Milica Martinović, Ana Žugić, Ivana Nešić, Stevan Blagojević, Nebojša Jasnić and Tomislav Tosti

Pharmaceutics 2024, 16(7), 962; https://doi.org/10.3390/pharmaceutics16070962 - 20 Jul 2024

Viewed by 1676

Abstract

L-ascorbic acid represents one of the most potent antioxidant, photoprotective, anti-aging, and anti-pigmentation cosmeceutical agents, with a good safety profile. However, the main challenge is the formulation of stable topical formulation products, which would optimize the penetrability of L-ascorbic acid through the skin. The aim of our research was to evaluate the performance of ascorbyl palmitate on the skin, incorporated in creams and emulgels (2%) as carriers, as well as to determine the impact of its incorporation into liposomes on the penetration profile of this ingredient. Tape stripping was used to study the penetration of ascorbyl palmitate into the stratum corneum. In addition, the sensory and textural properties of the formulations were determined. The liposomal formulations exhibited a better penetration profile (p < 0.05) of the active substance compared to the non-liposomal counterpart, leading to a 1.3-fold and 1.2 fold-increase in the total amount of penetrated ascorbyl palmitate in the stratum corneum for the emulgel and cream, respectively. Encapsulation of ascorbyl palmitate into liposomes led to an increase in the adhesiveness and density of the prepared cream and emulgel samples. The best spreadability and absorption during application were detected in liposomal samples. The obtained results confirmed that liposomal encapsulation of ascorbyl palmitate improved dermal penetration for both the cream and emulgel formulations. Full article

(This article belongs to the Special Issue Advances in Natural Products for Cutaneous Application)

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19 pages, 10658 KiB

Open AccessArticle

From Nature to Healing: Development and Evaluation of Topical Cream Loaded with Pine Tar for Cutaneous Wound Repair

by Branislav Petrovic, Anica Petrovic, Katarina Bijelic, Dragana Stanisic, Slobodanka Mitrovic, Vladimir Jakovljevic, Sergej Bolevich, Ivana Glisovic Jovanovic and Jovana Bradic

Pharmaceutics 2024, 16(7), 859; https://doi.org/10.3390/pharmaceutics16070859 - 26 Jun 2024

Cited by 1 | Viewed by 1869

Abstract

Despite the numerous efforts to find an appropriate therapeutic modality, diabetic wounds remain a global unsolved problem. Therefore, our study aimed to develop a topical formulation loaded with pine tar and to investigate its wound-healing capacity. After phytochemical profiling of pine tar, an oil-in-water emulsion with 1% pine tar was prepared. The physical, chemical, and microbiological stability of prepared pine tar cream (PTC) was assessed during six months. Additionally, safety potential was examined in healthy rats, while wound-healing potential was accessed by creating excision wounds in diabetic rats. Diabetic animals were divided into four groups: untreated or topically treated with either the cream base, PTC, or silver sulfadiazine cream. Wound healing was monitored at the following time points (0, 7, 14, and 21 days) through macroscopic, biochemical, and histological examinations. Our PTC formula showed good physicochemical properties and remained stable and compatible for cutaneous application. PTC showed a remarkable increase in wound closure rate and led to attenuation of morphological alterations in skin samples. These findings were associated with significantly improved redox status and enhanced hydroxyproline levels in PTC relative to the untreated and cream base groups. Our results demonstrated that PTC might serve as a promising tool for the management of diabetic wounds. Full article

(This article belongs to the Special Issue Advances in Natural Products for Cutaneous Application)

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18 pages, 3184 KiB

Open AccessArticle

Anti-Inflammatory Effects of the LK5 Herbal Complex on LPS- and IL-4/IL-13-Stimulated HaCaT Cells and a DNCB-Induced Animal Model of Atopic Dermatitis in BALB/c Mice

by Hyun-Jeong Kim, So-Yeon Kim, Ho Jung Bae, Yu-Yeong Choi, Ju-Yeon An, Ye Eun Cho, So-Young Cho, Su-Jung Lee, Sanghyun Lee, MinSub Sin, Young Min Yun, Jong Ryul Lee and Se Jin Park

Pharmaceutics 2024, 16(1), 40; https://doi.org/10.3390/pharmaceutics16010040 - 27 Dec 2023

Cited by 2 | Viewed by 2471

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease influenced by a complex interplay of genetic and environmental factors. The activation of the JAK-STAT pathway increases the expression of inflammatory cytokines such as IL-4 and IL-13, further deteriorating AD. Therefore, for the treatment of AD, the JAK-STAT pathway is emerging as a significant target, alongside inflammatory cytokines. This study investigates the potential therapeutic effects of a novel herbal complex, LK5, composed of Scutellaria baicalensis, Liriope platyphylla, Sophora flavescens, Dictammus dasycarpus, and Phellodendron schneider, known for their anti-inflammatory and immune-modulating properties. We examined the anti-inflammatory and anti-AD effects of the LK5 herbal complex in HaCaT cells stimulated by LPS and IL-4/IL-13, as well as in a mouse model of AD induced by DNCB. In HaCaT cells stimulated with LPS or IL-4/IL-13, the LK5 herbal complex demonstrated anti-inflammatory effects by inhibiting the expression of inflammatory cytokines including TNF-α, IL-6, and IL-1β, and downregulating the phosphorylation of STAT proteins. In a murine AD-like model induced by DNCB, administration of the LK5 herbal complex significantly ameliorated clinical symptoms, including dermatitis, ear thickness, and TEWL. Histological analysis revealed a reduction in epidermal thickness and mast cell infiltration. The LK5 herbal complex also inhibited pruritus induced by compound 48/80. Furthermore, the LK5 herbal complex treatment significantly decreased the levels of inflammatory cytokines such as TSLP, IL-6, and IgE in plasma and ear tissue of AD-induced mice. These findings suggest that the LK5 herbal complex may modulate the immune response and alleviate AD symptoms by inhibiting STAT pathways. Full article

(This article belongs to the Special Issue Advances in Natural Products for Cutaneous Application)

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30 pages, 9249 KiB

Open AccessArticle

Liposomal and Liposomes-Film Systems as Carriers for Bioactives from Paeonia tenuifolia L. Petals: Physicochemical Characterization and Biological Potential

by Natalija Čutović, Tatjana Marković, Tamara Carević, Dejan Stojković, Branko Bugarski and Aleksandra A. Jovanović

Pharmaceutics 2023, 15(12), 2742; https://doi.org/10.3390/pharmaceutics15122742 - 7 Dec 2023

Cited by 3 | Viewed by 1628

Abstract

Paeonia tenuifolia L. (steppe peony) petal extract was proficiently encapsulated into liposomes and biopolymer films in the current work, both times utilizing a single-step procedure. The encapsulation efficiency, size of the particles, and index of polydispersity (PDI), as well as the ζ potential of the obtained liposomes were determined, whereas in the case of films, the test included moisture content and mechanical property assessment. Fourier transform infrared spectroscopy (FT-IR) was used to evaluate the chemical composition and existence of numerous interactions in the systems. All the obtained encapsulates were subjected to antibacterial, antifungal and antibiofilm activity testing of the pathogens associated with human skin. The results indicated that the liposomes prepared using Phospholipon had the highest encapsulation efficiency (72.04%), making them the most favorable ones in the release study as well. The biological assays also revealed that Phospholipon was the most beneficial phospholipid mixture for the preparation of liposomes, whereas the film containing these liposomes did not have the ability to inhibit pathogen growth, making the double encapsulation of P. tenuifolia L. petal extract needless. These findings may be a first step toward the potential use of steppe peony extract-loaded films and liposomes in pharmaceutical and cosmetical industries. Full article

(This article belongs to the Special Issue Advances in Natural Products for Cutaneous Application)

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16 pages, 3564 KiB

Open AccessArticle

Topical Application of Siberian Pine Essential Oil Formulations Enhance Diabetic Wound Healing

by Milica Nikolic, Marijana Andjic, Jovana Bradic, Aleksandar Kocovic, Marina Tomovic, Andjela Milojevic Samanovic, Vladimir Jakovljevic, Mirjana Veselinovic, Ivan Capo, Veljko Krstonosic, Nebojsa Kladar and Anica Petrovic

Pharmaceutics 2023, 15(10), 2437; https://doi.org/10.3390/pharmaceutics15102437 - 9 Oct 2023

Cited by 9 | Viewed by 1791

Abstract

This study aimed to develop novel topical formulations based on a natural component (0.5% of Siberian pine essential oil) and to assess its wound-healing capacity through macroscopic, histopathological, and biochemical examination. The phytochemical profile of Pinus sibirica essential oil (PSEO) and rheological analysis and safety potential of formulations were determined. The wound-healing effect was evaluated on an excision wound model in diabetic Wistar albino rats randomly divided into the following groups topically treated with (1) untreated, (2) 1% silver sulfadiazine, (3) ointment base, (4) gel base, (5) PSEO ointment, and (6) PSEO gel. Formulations containing PSEO were stable and safe for skin application. Three weeks of treatment with both PSEO formulations (ointment and gel) led to a significant reduction in wound size (98.14% and 96.28%, respectively) and a remarkably higher level of total hydroxyproline content (9.69 µg/mg and 7.26 µg/mg dry tissue, respectively) relative to the control group (65.97%; 1.81 µg/mg dry tissue). These findings were in correlation with histopathological results. Topically applied PSEO formulations were associated with a significant reduction in most of the measured pro-oxidants and enhanced activity of the antioxidant defense system enzymes (p < 0.05). Our findings showed that gel and ointment with PSEO demonstrated significant wound-repairing capabilities in the excision wound model. Full article

(This article belongs to the Special Issue Advances in Natural Products for Cutaneous Application)

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Review

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24 pages, 2159 KiB

Open AccessReview

Comprehensive Insight into Cutaneous Application of Hemp

by Ana Žugić, Milica Martinović, Vanja Tadić, Miloš Rajković, Gordana Racić, Ivana Nešić and Anamarija Koren

Pharmaceutics 2024, 16(6), 748; https://doi.org/10.3390/pharmaceutics16060748 - 31 May 2024

Cited by 3 | Viewed by 1345

Abstract

Known for its natural bio-compounds and therapeutic properties, hemp is being utilized in the development of skin products. These products offer a wide range of applications and benefits in the fields of natural bio-compounds, pharmaceutical technology, topical delivery systems, and cosmeceuticals. This manuscript deals with hemp actives, such as cannabinoids, terpenes, and flavonoids, and their diverse biological properties relative to topical application, including anti-inflammatory, antimicrobial, and antioxidant effects. Also, the paper reviews strategies to overcome poor penetration of hemp actives, as well as the integration of hemp actives in cosmeceuticals that provide natural and sustainable alternatives to traditional skincare products offering a range of benefits, including anti-aging, moisturizing, and soothing properties. The review aims to provide a comprehensive understanding of the development and manufacturing processes of skin products containing hemp actives. By delving into the science behind hemp-based products, the paper provides valuable insights into the potential of hemp as a versatile ingredient in the pharmaceutical and cosmetic industries. The utilization of hemp in these innovative products not only offers therapeutic benefits but also promotes natural and sustainable approaches to skincare. Full article

(This article belongs to the Special Issue Advances in Natural Products for Cutaneous Application)

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16 pages, 1660 KiB

Open AccessReview

Biological Activity of Fermented Plant Extracts for Potential Dermal Applications

by Anna Herman and Andrzej Przemysław Herman

Pharmaceutics 2023, 15(12), 2775; https://doi.org/10.3390/pharmaceutics15122775 - 14 Dec 2023

Cited by 9 | Viewed by 3222

Abstract

Fermented plant extracts (FPEs) are functional liquids formed as a result of the fermentation of fresh plants by microorganisms, mainly bacteria and fungi. The appropriate selection of plants, microorganism strains, and conditions under which the fermentation process is carried out is very important in terms of obtaining a suitable matrix of biologically active compounds with different biological properties. The purpose of this review is to provide verified data on the current knowledge acquired regarding the biological activity of FPEs for cosmetic use and dermal applications. The antioxidant, antimicrobial, anti-inflammatory, anti-melanogenic, and wound-healing activity of FPEs, as well as their potential dermal applications, will be described. Full article

(This article belongs to the Special Issue Advances in Natural Products for Cutaneous Application)

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