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Nanoparticles and Microparticles in Drug Delivery

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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 (31 December 2023) | Viewed by 17408

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Prof. Dr. Varaporn Buraphacheep Junyaprasert

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Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand
Interests: nanoparticles and microparticles in drug delivery; polymer–drug conjugates; functionalized nanomaterials in cancer therapy; lipid nanocarriers for dermal delivery; nanocrystals

Special Issue Information

Dear Colleagues,

Nano- and micro-based drug delivery systems offer potential advantages in improving effective transport of active pharmaceuticals to target sites in a controlled manner. They overcome the limitations of active drugs, such as instability, burst and uncontrolled release, and nonspecific delivery. Applications of nano/microparticles in drug delivery have been reported in various routes of administration, such as oral, parenteral, dermal, inhalation, ocular, brain, sublingual and rectal, etc. Incorporation of drugs into nano/microcarriers leads to innovative delivery systems, such as lipid-based carriers, e.g., liposomes, nanoemulsions, microemulsions, self-microemulsifying drug delivery systems (SMEDDS), lipid nanoparticles (SLN and NLC), and polymer-based carriers, e.g. polymeric nanoparticles, dendrimers, and polymeric micelles. Nanocrystals are also included as one practical approach to improve the solubility and stability of poorly soluble drugs. Many researchers have focused their efforts on developing successful nano- and microdelivery systems to improve bioavailability, increase efficacy, and reduce toxicity. In this Special Issue, we invite all authors to report their research works or to contribute a review on recent advances in the area of nano- and micro-based drug delivery.

Prof. Dr. Varaporn Buraphacheep Junyaprasert
Guest Editor

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Keywords

nanoparticles in drug delivery
microparticles in drug delivery
drug delivery
lipid-based carriers
liposomes
nanoemulsions
microemulsions
self-microemulsifying drug delivery systems (MEDDS)
lipid nanoparticles
polymer-based carriers
polymeric nanoparticles
dendrimers
polymeric micelles
nanocrystals

Published Papers (9 papers)

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Research

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28 pages, 5380 KiB

Open AccessArticle

The Effect of High-Pressure Homogenization Conditions on the Physicochemical Properties and Stability of Designed Fluconazole-Loaded Ocular Nanoemulsions

by Agnieszka Gawin-Mikołajewicz, Urszula Nawrot, Katarzyna Hanna Malec, Karolina Krajewska, Karol Przemysław Nartowski and Bożena Lucyna Karolewicz

Pharmaceutics 2024, 16(1), 11; https://doi.org/10.3390/pharmaceutics16010011 - 20 Dec 2023

Viewed by 1119

Abstract

The growing interest in high-energy emulsification is a result of its scalability, which is important from an industrial perspective and allows for a more reproducible and efficient production of pharmaceutical formulations. The aim of this study was to evaluate the effect of composition, mainly a fixed surfactant/cosurfactant (S_mix) ratio, their concentration, and the parameters of high-pressure homogenization (HPH) processing on the quality and stability of ophthalmic fluconazole-loaded nanoemulsions. After a physicochemical analysis of nanoemulsions containing 20% w/w of oil, as optimal conditions for the HPH process, three cycles at a pressure of 1000 bar were established, obtaining formulations with an average droplet diameter size in the range of 80.63–129.68 nm and PDI values below 0.25. While it was expected that an increasing cosurfactant concentration decreased the droplet size, in the case of formulations containing Tween 20 and 10% w/w of cosurfactants, “over-processing” was observed, identified by the droplet size and polydispersity index increase. Consecutively, the selected formulations were evaluated for in vitro drug release in Franz’s cell, antifungal activity, and 30-day stability using NMR spectroscopy. An antifungal activity test showed no significant difference in the antifungal activity between optimal fluconazole-loaded nanoemulsions and a 0.3% aqueous drug solution, but previously, research showed that prepared formulations were characterized by a higher viscosity and satisfactory prolonged release compared to a control. In a 30-day stability study, it was observed that higher HLB values of the used surfactants decreased the stability of the formulations in the following order: Kolliphor EL, Tween 80, Tween 20. The NMR spectra confirmed that Kolliphor EL-based formulations ensured the higher stability of the nanoemulsion composition in comparison to Tween 80 and a better stabilizing effect of propylene glycol as a cosurfactant in comparison to PEG 200. Therefore, the optimization of HPH technology should be focused on the selection of S_mix and the S_mix:oil ratio in order to prepare stable formulations of high quality. Full article

(This article belongs to the Special Issue Nanoparticles and Microparticles in Drug Delivery)

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15 pages, 3183 KiB

Open AccessArticle

Influence of Dose, Particle Size and Concentration on Dermal Penetration Efficacy of Curcumin

by Em-on Chaiprateep, Sabrina Wiemann, Ralph W. Eckert, Christian Raab, Soma Sengupta and Cornelia M. Keck

Pharmaceutics 2023, 15(11), 2645; https://doi.org/10.3390/pharmaceutics15112645 - 20 Nov 2023

Cited by 1 | Viewed by 814

Abstract

The influence of size, particle concentration and applied dose (finite vs. infinite dose) on the dermal penetration efficacy of curcumin was investigated in this study. For this, curcumin suspensions with different particle sizes (approx. 20 µm and approx. 250 nm) were produced in different concentrations (0.625–5% (w/w)). The dermal penetration efficacy was determined semi-quantitatively on the ex vivo porcine ear model. The results demonstrated that the presence of particles increases the dermal penetration efficacy of the active compounds being dissolved in the water phase of the formulation. The reason for this is the formation of an aqueous meniscus that develops between particles and skin due to the partial evaporation of water from the vehicle after topical application. The aqueous meniscus contains dissolved active ingredients, and therefore creates a small local spot with a locally high concentration gradient that leads to improved dermal penetration. The increase in penetration efficacy depends on the number of particles in the vehicle, i.e., higher numbers of particles and longer contact times lead to higher penetration efficacy. Therefore, nanocrystals with a high particle concentration were found to be the most suitable formulation principle for efficient and deep dermal penetration of poorly water-soluble active ingredients. Full article

(This article belongs to the Special Issue Nanoparticles and Microparticles in Drug Delivery)

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23 pages, 16779 KiB

Open AccessArticle

Modification of Poly(Glycerol Adipate) with Tocopherol and Cholesterol Modulating Nanoparticle Self-Assemblies and Cellular Responses of Triple-Negative Breast Cancer Cells to SN-38 Delivery

by Jiraphong Suksiriworapong, Chittin Achayawat, Phutthikom Juangrattanakamjorn, Vincenzo Taresco, Valentina Cuzzucoli Crucitti, Krisada Sakchaisri and Somnuk Bunsupa

Pharmaceutics 2023, 15(8), 2100; https://doi.org/10.3390/pharmaceutics15082100 - 08 Aug 2023

Cited by 4 | Viewed by 1388

Abstract

This study aimed to fabricate new variations of glycerol-based polyesters by grafting poly(glycerol adipate) (PGA) with hydrophobic bioactive moieties, tocopherol (TOC), and cholesterol (CHO). Their effects on nanoparticle (NP) formation, drug release, and cellular responses in cancer and normal cells were evaluated. CHO and TOC were successfully grafted onto PGA backbones with 30% and 50% mole grafting. Increasing the percentage of mole grafting in both molecules increased the glass transition temperature and water contact angle of the final polymers but decreased the critical micelle concentration of the formulated particles. PGA-TOC NPs reduced the proliferation of MDA-MB-231 cancer cells. However, they enhanced the proliferation of primary dermal fibroblasts within a specific concentration range. PGA-CHO NPs minimally affected the growth of cancer and normal cells. Both types of NPs did not affect apoptosis or the cell cycle of cancer cells. PGA-CHO and PGA-TOC NPs were able to entrap SN-38, a hydrophobic anticancer drug, with a particle size <200 nm. PGA-CHO NPs had a higher drug loading capacity and a greater drug release than PGA-TOC NPs. However, SN-38-loaded PGA-TOC NPs showed higher toxicity than SN-38 and SN-38-loaded PGA-CHO NPs due to the combined effects of antiproliferation and higher cellular uptake. Compared with SN-38, the drug-loaded NPs more profoundly induced sub-G1 in the cell cycle analysis and apoptosis of cancer cells in a similar pattern. Therefore, PGA-CHO and PGA-TOC polymers have potential applications as delivery systems for anticancer drugs. Full article

(This article belongs to the Special Issue Nanoparticles and Microparticles in Drug Delivery)

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17 pages, 2183 KiB

Open AccessArticle

Polysarcosine-Functionalized mRNA Lipid Nanoparticles Tailored for Immunotherapy

by Christoph Wilhelmy, Isabell Sofia Keil, Lukas Uebbing, Martin A. Schroer, Daniel Franke, Thomas Nawroth, Matthias Barz, Ugur Sahin, Heinrich Haas, Mustafa Diken and Peter Langguth

Pharmaceutics 2023, 15(8), 2068; https://doi.org/10.3390/pharmaceutics15082068 - 01 Aug 2023

Cited by 7 | Viewed by 3503

Abstract

Lipid nanoparticles (LNPs) have gained great attention as carriers for mRNA-based therapeutics, finding applications in various indications, extending beyond their recent use in vaccines for infectious diseases. However, many aspects of LNP structure and their effects on efficacy are not well characterized. To further exploit the potential of mRNA therapeutics, better control of the relationship between LNP formulation composition with internal structure and transfection efficiency in vitro is necessary. We compared two well-established ionizable lipids, namely DODMA and MC3, in combination with two helper lipids, DOPE and DOPC, and two polymer-grafted lipids, either with polysarcosine (pSar) or polyethylene glycol (PEG). In addition to standard physicochemical characterization (size, zeta potential, RNA accessibility), small-angle X-ray scattering (SAXS) was used to analyze the structure of the LNPs. To assess biological activity, we performed transfection and cell-binding assays in human peripheral blood mononuclear cells (hPBMCs) using Thy1.1 reporter mRNA and Cy5-labeled mRNA, respectively. With the SAXS measurements, we were able to clearly reveal the effects of substituting the ionizable and helper lipid on the internal structure of the LNPs. In contrast, pSar as stealth moieties affected the LNPs in a different manner, by changing the surface morphology towards higher roughness. pSar LNPs were generally more active, where the highest transfection efficiency was achieved with the LNP formulation composition of MC3/DOPE/pSar. Our study highlights the utility of pSar for improved mRNA LNP products and the importance of pSar as a novel stealth moiety enhancing efficiency in future LNP formulation development. SAXS can provide valuable information for the rational development of such novel formulations by elucidating structural features in different LNP compositions. Full article

(This article belongs to the Special Issue Nanoparticles and Microparticles in Drug Delivery)

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21 pages, 5668 KiB

Open AccessArticle

Formulation and Evaluation of Prednisolone Sodium Metazoate-Loaded Mucoadhesive Quatsomal Gel for Local Treatment of Recurrent Aphthous Ulcers: Optimization, In Vitro, Ex Vivo, and In Vivo Studies

by Ashraf Kassem, Hanan Refai, Mohamed A. El-Nabarawi and Menna M. Abdellatif

Pharmaceutics 2023, 15(7), 1947; https://doi.org/10.3390/pharmaceutics15071947 - 14 Jul 2023

Viewed by 1298

Abstract

This study aims to formulate a buccal mucoadhesive gel containing prednisolone sodium metazoate-loaded quatsomes for efficient localized therapy of recurrent aphthous ulcers. Quatsomes were prepared using a varied concentration of quaternary ammonium surfactants (QAS) and cholesterol (CHO). A 2³ factorial design was conducted to address the impact of independent variables QAS type (X₁), QAS to CHO molar ratio (X₂), and sonication time (X₃). The dependent variables were particle size (PS; Y₁), polydispersity index (PDI; Y₂), zeta potential (ZP; Y₃), entrapment efficiency percent (EE%; Y₄) and percent of drug released after 6 h (Q6%: Y₅). Then, the selected quatsomes formula was incorporated into different gel bases to prepare an optimized mucoadhesive gel to be evaluated via in vivo study. The PS of the developed quatsomes ranged from 69.47 ± 0.41 to 113.28 ± 0.79 nm, the PDI from 0.207 ± 0.004 to 0.328 ± 0.004, ZP from 45.15 ± 0.19 to 68.1 ± 0.54 mV, EE% from 79.62 ± 1.44 to 98.60% ± 1.22 and Q6% from 58.39 ± 1.75 to 94.42% ± 2.15. The quatsomal mucoadhesive gel showed rapid recovery of ulcers, which was confirmed by the histological study and the evaluation of inflammatory biomarkers. These results assured the capability of the developed quatsomal mucoadhesive gel to be a promising formulation for treating buccal diseases. Full article

(This article belongs to the Special Issue Nanoparticles and Microparticles in Drug Delivery)

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18 pages, 4338 KiB

Open AccessArticle

Development of Miconazole-Loaded Microemulsions for Enhanced Topical Delivery and Non-Destructive Analysis by Near-Infrared Spectroscopy

by Chutima Phechkrajang, Wichuda Phiphitphibunsuk, Rapee Sukthongchaikool, Nantana Nuchtavorn and Jiraporn Leanpolchareanchai

Pharmaceutics 2023, 15(6), 1637; https://doi.org/10.3390/pharmaceutics15061637 - 01 Jun 2023

Cited by 3 | Viewed by 1486

Abstract

The antifungal drug miconazole nitrate has a low solubility in water, leading to reduced therapeutic efficacy. To address this limitation, miconazole-loaded microemulsions were developed and assessed for topical skin delivery, prepared through spontaneous emulsification with oleic acid and water. The surfactant phase included a mixture of polyoxyethylene sorbitan monooleate (PSM) and various cosurfactants (ethanol, 2-(2-ethoxyethoxy) ethanol, or 2-propanol). The optimal miconazole-loaded microemulsion containing PSM and ethanol at a ratio of 1:1 showed a mean cumulative drug permeation of 87.6 ± 5.8 μg/cm² across pig skin. The formulation exhibited higher cumulative permeation, permeation flux, and drug deposition than conventional cream and significantly increased the in vitro inhibition of Candida albicans compared with cream (p < 0.05). Over the course of a 3-month study conducted at a temperature of 30 ± 2 °C, the microemulsion exhibited favorable physicochemical stability. This outcome signifies its potential suitability as a carrier for effectively administering miconazole through topical administration. Additionally, a non-destructive technique employing near-infrared spectroscopy coupled with a partial least-squares regression (PLSR) model was developed to quantitatively analyze microemulsions containing miconazole nitrate. This approach eliminates the need for sample preparation. The optimal PLSR model was derived by utilizing orthogonal signal correction pretreated data with one latent factor. This model exhibited a remarkable R² value of 0.9919 and a root mean square error of calibration of 0.0488. Consequently, this methodology holds potential for effectively monitoring the quantity of miconazole nitrate in various formulations, including both conventional and innovative ones. Full article

(This article belongs to the Special Issue Nanoparticles and Microparticles in Drug Delivery)

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18 pages, 2504 KiB

Open AccessArticle

Cannabidiol-Loaded Nanostructured Lipid Carriers (NLCs) for Dermal Delivery: Enhancement of Photostability, Cell Viability, and Anti-Inflammatory Activity

by Boontida Morakul, Varaporn Buraphacheep Junyaprasert, Krisada Sakchaisri and Veerawat Teeranachaideekul

Pharmaceutics 2023, 15(2), 537; https://doi.org/10.3390/pharmaceutics15020537 - 06 Feb 2023

Cited by 6 | Viewed by 2015

Abstract

The aim of this study was to encapsulate cannabidiol (CBD) extract in nanostructured lipid carriers (NLCs) to improve the chemical stability and anti-inflammatory activity of CBD for dermal delivery. CBD-loaded NLCs (CBD-NLCs) were prepared using cetyl palmitate (CP) as a solid lipid and stabilized with Tego^® Care 450 (TG450) or poloxamer 188 (P188) by high-pressure homogenization (HPH). The CBD extract was loaded at 1% w/w. Three different oils were employed to produce CBD-NLCs, including Transcutol^® P, medium-chain triglycerides (MCT), and oleic acid (OA). CBD-NLCs were successfully prepared with an entrapment efficiency (E.E.) of 100%. All formulations showed particle sizes between 160 and 200 nm with PDIs less than 0.10. The type of surfactant and oil used affected the particle sizes, zeta potential, and crystallinity of the CBD-NLCs. CBD-NLCs stabilized with TG450 showed higher crystallinity after production and storage at 30 °C for 30 days as compared to those with P188. Encapsulation of the CBD extract in NLCs enhanced its chemical stability after exposure to simulated sunlight (1000 kJ/m²) compared to that of the CBD extract in ethanolic solution. The CBD-NLCs prepared from MCT and OA showed slower CBD release compared with that from Transcutol^® P, and the kinetic data for release of CBD from CBD-NLCs followed Higuchi’s release model with a high coefficient of determination (>0.95). The extent of CBD permeation through Strat-M^® depended on the oil type. The cytotoxicity of the CBD extract on HaCaT and HDF cells was reduced by encapsulation in the NLCs. The anti-inflammatory activity of the CBD extract in RAW264.7 cell macrophages was enhanced by encapsulation in CBD-NLCs prepared from MCT and OA. Full article

(This article belongs to the Special Issue Nanoparticles and Microparticles in Drug Delivery)

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Review

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26 pages, 5110 KiB

Open AccessReview

Innovative Design of Targeted Nanoparticles: Polymer–Drug Conjugates for Enhanced Cancer Therapy

by Varaporn Buraphacheep Junyaprasert and Parichart Thummarati

Pharmaceutics 2023, 15(9), 2216; https://doi.org/10.3390/pharmaceutics15092216 - 27 Aug 2023

Cited by 8 | Viewed by 2328

Abstract

Polymer–drug conjugates (PDCs) have shown great promise in enhancing the efficacy and safety of cancer therapy. These conjugates combine the advantageous properties of both polymers and drugs, leading to improved pharmacokinetics, controlled drug release, and targeted delivery to tumor tissues. This review provides a comprehensive overview of recent developments in PDCs for cancer therapy. First, various types of polymers used in these conjugates are discussed, including synthetic polymers, such as poly(↋-caprolactone) (PCL), D-α-tocopheryl polyethylene glycol (TPGS), and polyethylene glycol (PEG), as well as natural polymers such as hyaluronic acid (HA). The choice of polymer is crucial to achieving desired properties, such as stability, biocompatibility, and controlled drug release. Subsequently, the strategies for conjugating drugs to polymers are explored, including covalent bonding, which enables a stable linkage between the polymer and the drug, ensuring controlled release and minimizing premature drug release. The use of polymers can extend the circulation time of the drug, facilitating enhanced accumulation within tumor tissues through the enhanced permeability and retention (EPR) effect. This, in turn, results in improved drug efficacy and reduced systemic toxicity. Moreover, the importance of tumor-targeting ligands in PDCs is highlighted. Various ligands, such as antibodies, peptides, aptamers, folic acid, herceptin, and HA, can be incorporated into conjugates to selectively deliver the drug to tumor cells, reducing off-target effects and improving therapeutic outcomes. In conclusion, PDCs have emerged as a versatile and effective approach to cancer therapy. Their ability to combine the advantages of polymers and drugs offers enhanced drug delivery, controlled release, and targeted treatment, thereby improving the overall efficacy and safety of cancer therapies. Further research and development in this field has great potential to advance personalized cancer treatment options. Full article

(This article belongs to the Special Issue Nanoparticles and Microparticles in Drug Delivery)

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34 pages, 3003 KiB

Open AccessReview

Critical Review in Designing Plant-Based Anticancer Nanoparticles against Hepatocellular Carcinoma

by Aalok Basu, Thanaphon Namporn and Pakatip Ruenraroengsak

Pharmaceutics 2023, 15(6), 1611; https://doi.org/10.3390/pharmaceutics15061611 - 29 May 2023

Cited by 2 | Viewed by 2490

Abstract

Hepatocellular carcinoma (HCC), accounting for 85% of liver cancer cases, continues to be the third leading cause of cancer-related deaths worldwide. Although various forms of chemotherapy and immunotherapy have been investigated in clinics, patients continue to suffer from high toxicity and undesirable side effects. Medicinal plants contain novel critical bioactives that can target multimodal oncogenic pathways; however, their clinical translation is often challenged due to poor aqueous solubility, low cellular uptake, and poor bioavailability. Nanoparticle-based drug delivery presents great opportunities in HCC therapy by increasing selectivity and transferring sufficient doses of bioactives to tumor areas with minimal damage to adjacent healthy cells. In fact, many phytochemicals encapsulated in FDA-approved nanocarriers have demonstrated the ability to modulate the tumor microenvironment. In this review, information about the mechanisms of promising plant bioactives against HCC is discussed and compared. Their benefits and risks as future nanotherapeutics are underscored. Nanocarriers that have been employed to encapsulate both pure bioactives and crude extracts for application in various HCC models are examined and compared. Finally, the current limitations in nanocarrier design, challenges related to the HCC microenvironment, and future opportunities are also discussed for the clinical translation of plant-based nanomedicines from bench to bedside. Full article

(This article belongs to the Special Issue Nanoparticles and Microparticles in Drug Delivery)

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