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Nanoparticles for Local Drug Delivery

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

Deadline for manuscript submissions: closed (31 December 2024) | Viewed by 22784

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Prof. Dr. Snezana Savic

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Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
Interests: nanoplatforms for brain and skin delivery; innovative biocompatible excipients; poorly water-soluble drugs; physicochemical/in vitro/in silico characterization methods; in vivo pharmacokinetics in rats
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Dr. Tanja Ilić

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Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia
Interests: lipid nanosystems for localized drug delivery (brain, skin); formulation development; physicochemical characterization methods; in vitro drug permeation through biological barriers (blood–brain barrier, skin); in vivo (dermo) pharmacokinetics

Dr. Sanela Savic

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Faculty of Technology in Leskovac, University of Niš, Bulevar Oslobodjenja 124, 16000 Leskovac, Serbia
Interests: lipid nanosystems; experimental design; brain targeting; in vivo pharmacokinetics; skin delivery; skin bioengineering techniques; safety and efficacy testing

Special Issue Information

Dear Colleagues,

Despite increasing advances in the design and development of modern drug delivery systems and technologies, the effective treatment of many diseases/disorders such as cancer, neurodegenerative and neuromuscular disorders, inflammatory diseases and infections (to name a few) still remains a major challenge due to the presence of restrictive biological barriers (such as the mucosal epithelium in the intestine, lungs, nose and mouth, skin, blood–brain barrier, blood–retinal barrier). To deliver a sufficient therapeutic concentration of a drug at the intended site of action (diseased organ/tissue/target cells) in a predictable/controlled manner, thereby avoiding/reducing off-site toxicity and systemic adverse effects, local drug delivery strategies have been established as a promising approach. Recently, significant progress has been made in the field of local drug delivery, achieved either through local or systemic administration (targeted/triggered approach), largely due to the implementation of nanoparticles. Although diverse types of nanoparticles (lipid-based, polymeric, metallic, carbon nanotubes, dendrimers, etc.) have been developed for local/targeted/triggered delivery of various therapeutics (anticancer drugs, central nervous system drugs, anti-inflammatory drugs, antimicrobial agents, hormones, nucleic acids, etc.) via different routes of administration (e.g., intratumoral, intra-articular, (intra)nasal, (intra)ocular, (trans)dermal, (intra)oral, oromucosal, sublingual, dental, pulmonary/inhalation, vaginal/uterine, etc.), additional efforts are required to optimize drug incorporation and release, formulation stability and shelf-life, biocompatibility, safety, biodistribution and targeting, giving this topic permanent and growing interest.

We warmly invite researchers to share their ideas, insights and perspectives from the dynamic landscape of nanoparticles for local drug delivery, covering a wide range of topics related to the following areas, among others: formulation and optimization of drug-containing nanoparticles, passive/active targeting and triggering approaches for site-specific or site-avoidance drug delivery, controlled release mechanisms and kinetics, in vitro/in vivo fate and interactions with the biological environment, biocompatibility and safety assessments, clinical applications and translational research.

Prof. Dr. Snezana Savic
Dr. Tanja Ilić
Dr. Sanela Savic
Guest Editors

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Keywords

lipid nanoparticles
polymeric nanoparticles
inorganic nanoparticles
localized administration routes
targeted/triggered drug delivery
critical quality attributes
biocompatibility
clinical application and translation

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Published Papers (8 papers)

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Research

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13 pages, 6924 KiB

Open AccessArticle

Evaluation of Nano-Niclosamide in Killing Demodex folliculorum In Vitro and the Potential Application in Ocular Surface

by Jiani Li, Panqin Ma, Shujia Guo, Danyi Qin, Yuqian Wang, Yuwen Liu, Zixuan Yang, Caihong Huang, Yi Han and Zuguo Liu

Pharmaceutics 2025, 17(3), 332; https://doi.org/10.3390/pharmaceutics17030332 - 4 Mar 2025

Viewed by 723

Abstract

Background/Objectives: Blepharitis is a condition often caused by Demodex folliculorum infestations, resulting in significant ocular discomfort and surface damage. Current treatments offer only temporary relief and fail to eliminate mites effectively. This study evaluates nano-niclosamide (nano-NCL), a lipophilic nanosuspension designed to enhance solubility and permeability, for targeting Demodex folliculorum. Methods: Nano-NCL was characterized by particle size, zeta potential, transmission electron microscopy, pH measurement, bacterial culture, and HPLC. Viable Demodex mites were collected from patients’ eyelashes and assigned to six treatment groups: DDW, F127, 0.15% nano-NCL, 0.3% nano-NCL, 20% TTO, and Okra. Mite survival was analyzed using Kaplan–Meier curves. The ocular surface safety was assessed via slit-lamp examination, corneal fluorescein staining, and in vivo confocal microscopy. Results: The nano-NCL particles are uniformly rod-shaped, approximately 291 nm in size, and exhibit good stability, remaining suspended in various media for up to 20 days. The formulation has a stable pH of 6 and demonstrated no bacterial growth, indicating sterility and suitability for clinical use. In vitro, both 0.15% (w/v) and 0.30% (w/v) nano-NCL significantly reduced Demodex survival, with mortality rates ranging from 70.6% to 92.3% within 2 h. Safety evaluations showed minimal corneal staining and inflammation. Notably, 0.15% nano-NCL displayed efficacy comparable to that of 20% tea tree oil (TTO) and Okra, which are established anti-Demodex treatments. Conclusions: Nano-NCL, particularly at 0.15%, rapidly eliminates mites while maintaining excellent ocular tolerability, making it a promising treatment for Demodex-related ocular surface diseases. Full article

(This article belongs to the Special Issue Nanoparticles for Local Drug Delivery)

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15 pages, 1664 KiB

Open AccessArticle

Nanoparticle-in-Hydrogel Delivery System for the Sequential Release of Two Drugs

by Demian van Straten, Jaime Fernández Bimbo, Wim E. Hennink, Tina Vermonden and Raymond M. Schiffelers

Pharmaceutics 2025, 17(1), 127; https://doi.org/10.3390/pharmaceutics17010127 - 17 Jan 2025

Viewed by 1144

Abstract

Background/Objectives: Glioblastoma is the most common and lethal primary brain tumor. Patients often suffer from tumor- and treatment induced vasogenic edema, with devastating neurological consequences. Intracranial edema is effectively treated with dexamethasone. However, systemic dexamethasone requires large doses to surpass the blood brain barrier in therapeutic quantities, which is associated with significant side effects. The aim of this study was to investigate a biodegradable, dextran-hydroxyethyl methacrylate (dex-HEMA) based hydrogel, containing polymeric micelles loaded with dexamethasone and liposomes encapsulating dexamethasone phosphate for localized and prolonged delivery. Methods: Poly(ethylene glycol)-b-poly(N-2-benzoyloxypropyl methacrylamide (mPEG-b-p(HPMA-Bz)) micelles were loaded with dexamethasone and characterized. The dexamethasone micelles, together with dexamethasone phosphate liposomes, were dispersed in an aqueous dex-HEMA solution followed by radical polymerization using a photoinitiator in combination with light. The kinetics and mechanisms of drug release from this hydrogel were determined. Results: The diameter of the nanoparticles was larger than the mesh size of the hydrogel, rendering them immobilized in the polymer network. The micelles immediately released free dexamethasone from the hydrogel for two weeks. The dexamethasone phosphate loaded in the liposomes was not released until the gel degraded and intact liposomes were released, starting after 15 days. The different modes of release result in a biphasic and sequential release profile of dexamethasone followed by dexamethasone phosphate liposomes. Conclusions: The results show that this hydrogel system loaded with both dexamethasone polymeric micelles and dexamethasone phosphate loaded liposomes has potential as a local delivery platform for the sequential release of dexamethasone and dexamethasone phosphate, for the intracranial treatment of glioblastoma associated edema. Full article

(This article belongs to the Special Issue Nanoparticles for Local Drug Delivery)

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26 pages, 5586 KiB

Open AccessArticle

Quality by Design (QbD)-Driven Development and Optimization of Tacrolimus-Loaded Microemulsion for the Treatment of Skin Inflammation

by Sanjida Ahmed Srishti, Paromita Paul Pinky, Ryan Taylor, Jacob Guess, Natasha Karlik and Jelena M. Janjic

Pharmaceutics 2024, 16(12), 1487; https://doi.org/10.3390/pharmaceutics16121487 - 21 Nov 2024

Viewed by 1130

Abstract

Background: Skin inflammation represents a hallmark of many skin conditions, from psoriasis to eczema. Here, we present a novel microemulsion formulation for delivering a low dose of potent immunosuppressant, tacrolimus, to the skin for local inflammation control. The efficacy of topically delivered tacrolimus in controlling skin inflammation can be enhanced by packaging it into microemulsions. Microemulsions are small-size, thermodynamically stable, and surfactant-rich emulsions that can enhance tissue penetration and local tissue retention of poorly soluble drugs, which can reduce dosing frequency and potentially improve patient compliance. Methods: We present a novel approach for microemulsion manufacturing that uses a combination of both low and high-energy methods. The microemulsion composition and manufacturing parameters were optimized by adopting Quality by Design methodologies. The FMECA (Failure, Mode, Effects, Criticality Analysis)-based risk assessment, D-optimal Design of Experiment (DoE), and statistical analysis of parameters impacting responses through the multiple linear regression (MLR) was implemented for identifying critical formulation and process parameters. Results: Through QbD strategy, a stable microemulsion with optimized drug loading that met all critical quality attributes (CQAs) was identified. The optimal microemulsion candidate was successfully scaled up three-fold with retained CQAs. The presented microemulsion showed a slow and extended drug release profile in vitro. Conclusions: Presented findings suggest that microemulsions are a promising novel approach for tacrolimus delivery to the skin. Further, we also demonstrated that a combination of low-energy emulsification and microfluidization processes can produce stable and robust microemulsions with small droplet size that can be implemented in drug delivery of poorly soluble anti-inflammatory drugs. To the best of our knowledge, this is the first report of QbD-driven optimization of microemulsion manufacturing by microfluidization. Full article

(This article belongs to the Special Issue Nanoparticles for Local Drug Delivery)

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14 pages, 6702 KiB

Open AccessArticle

Antimicrobial Peptide Octoprohibitin-Encapsulated Chitosan Nanoparticles Enhanced Antibacterial Activity against Acinetobacter baumannii

by E. H. T. Thulshan Jayathilaka, Jinwook Han, Mahanama De Zoysa and Ilson Whang

Pharmaceutics 2024, 16(10), 1245; https://doi.org/10.3390/pharmaceutics16101245 - 25 Sep 2024

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Abstract

Background: This study focused on evaluating the physiochemical characteristics and antibacterial activity of Octoprohibitin-encapsulated CNPs (Octoprohibitin-CNPs) against Acinetobacter baumannii. Methods: Octoprohibitin was encapsulated into CNPs via ionotropic gelation with carboxymethyl chitosan (CMC) and low molecular weight chitosan (CS). Octoprohibitin-CNPs were dispersed in phosphate-buffered saline and the release kinetic profile was determined. Then Octoprohibitin-CNPs were examined using field-emission transmission electron microscopy and physicochemical characterization was performed. Antibacterial activity of Octoprohibitin-CNPs against A. baumannii was evaluated. Biofilm inhibition and eradication assays were performed using the crystal violet (CV) staining-based method for biofilm quantification. Results: The average diameter, zeta potential, encapsulation efficiency, and loading capacity of Octoprohibitin-CNPs were 244.5 ± 21.97 nm, +48.57 ± 0.38 mV, and 85.7% and 34.2%, respectively. TEM analysis imaging revealed that Octoprohibitin-CNPs are irregularly shaped, with fewer aggregates than CNPs. Octoprohibitin-CNPs exhibited a biphasic release pattern, characterized by an initial rapid phase followed by a sustained release over time, extending up to 93.68 ± 6.48% total release until 96 h. In vitro, Octoprohibitin-CNPs showed lower cytotoxicity compared to Octoprohibitin alone. Time-kill kinetic and bacterial viability reduction assays showed Octoprohibitin-CNPs exhibited slightly higher antibacterial activity against A. baumannii than Octoprohibitin. Conclusions: Octoprohibitin-CNP-treated A. baumannii exhibited higher levels of morphological deviation, increased membrane permeability, and the production of reactive oxygen species, as well as antibiofilm activity with greater biofilm inhibition and eradication than Octoprohibitin. These findings show that Octoprohibitin-CNPs perform better against A. baumannii compared to Octoprohibitin alone. Full article

(This article belongs to the Special Issue Nanoparticles for Local Drug Delivery)

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25 pages, 41882 KiB

Open AccessArticle

Chitosan Alginate Nanoparticles of Protein Hydrolysate from Acheta domesticus with Enhanced Stability for Skin Delivery

by Kankanit Yeerong, Panuwan Chantawannakul, Songyot Anuchapreeda, Saranya Juntrapirom, Watchara Kanjanakawinkul, Anette Müllertz, Thomas Rades and Wantida Chaiyana

Pharmaceutics 2024, 16(6), 724; https://doi.org/10.3390/pharmaceutics16060724 - 28 May 2024

Cited by 2 | Viewed by 2149

Abstract

This study aimed to develop chitosan alginate nanoparticles (CANPs) for enhanced stability for dermal delivery of protein hydrolysate from Acheta domesticus (PH). CANPs, developed using ionotropic pre-gelation followed by the polyelectrolyte complex technique, were characterized for particle size, polydispersity index (PDI), and zeta potential. After the incorporation of PH into CANPs, a comprehensive assessment included encapsulation efficiency, loading capacity, morphology, chemical analyses, physical and chemical stability, irritation potential, release profile, skin permeation, and skin retention. The most optimal CANPs, comprising 0.6 mg/mL sodium alginate, 1.8 mg/mL calcium chloride, and 0.1 mg/mL chitosan, exhibited the smallest particle size (309 ± 0 nm), the narrowest PDI (0.39 ± 0.01), and pronounced negative zeta potential (−26.0 ± 0.9 mV), along with an encapsulation efficiency of 56 ± 2%, loading capacity of 2.4 ± 0.1%, release of 40 ± 2% after 48 h, and the highest skin retention of 12 ± 1%. The CANPs induced no irritation and effectively enhanced the stability of PH from 44 ± 5% of PH remaining in a solution to 74 ± 4% after three-month storage. Therefore, the findings revealed the considerable potential of CANPs in improving PH stability and skin delivery, with promising applications in cosmetics and related fields. Full article

(This article belongs to the Special Issue Nanoparticles for Local Drug Delivery)

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27 pages, 4694 KiB

Open AccessArticle

Thermosensitive Polymeric Nanoparticles for Drug Co-Encapsulation and Breast Cancer Treatment

by Vanessa Franco Carvalho Dartora, Julia S. Passos, Leticia V. Costa-Lotufo, Luciana B. Lopes and Alyssa Panitch

Pharmaceutics 2024, 16(2), 231; https://doi.org/10.3390/pharmaceutics16020231 - 5 Feb 2024

Cited by 3 | Viewed by 2497

Abstract

Despite advances in breast cancer treatment, there remains a need for local management of noninvasive, low-grade ductal carcinoma in situ (DCIS). These focal lesions are well suited for local intraductal treatment. Intraductal administration supported target site drug retention, improved efficacy, and reduced systemic exposure. Here, we used a poly(N-isopropyl acrylamide, pNIPAM) nanoparticle delivery system loaded with cytotoxic piplartine and an MAPKAP Kinase 2 inhibitor (YARA) for this purpose. For tumor environment targeting, a collagen-binding peptide SILY (RRANAALKAGELYKSILYGSG-hydrazide) was attached to pNIPAM nanoparticles, and the nanoparticle diameter, zeta potential, drug loading, and release were assessed. The system was evaluated for cytotoxicity in a 2D cell culture and 3D spheroids. In vivo efficacy was evaluated using a chemical carcinogenesis model in female Sprague–Dawley rats. Nanoparticle delivery significantly reduced the IC₅₀ of piplartine (4.9 times) compared to the drug in solution. The combination of piplartine and YARA in nanoparticles further reduced the piplartine IC₅₀ (~15 times). Treatment with these nanoparticles decreased the in vivo tumor incidence (5.2 times). Notably, the concentration of piplartine in mammary glands treated with nanoparticles (35.3 ± 22.4 μg/mL) was substantially higher than in plasma (0.7 ± 0.05 μg/mL), demonstrating targeted drug retention. These results indicate that our nanocarrier system effectively reduced tumor development with low systemic exposure. Full article

(This article belongs to the Special Issue Nanoparticles for Local Drug Delivery)

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47 pages, 3150 KiB

Open AccessEditor’s ChoiceReview

Progress in Topical and Transdermal Drug Delivery Research—Focus on Nanoformulations

by Dominique Lunter, Victoria Klang, Adina Eichner, Sanela M. Savic, Snezana Savic, Guoping Lian and Franciska Erdő

Pharmaceutics 2024, 16(6), 817; https://doi.org/10.3390/pharmaceutics16060817 - 16 Jun 2024

Cited by 7 | Viewed by 4949

Abstract

Skin is the largest organ and a multifunctional interface between the body and its environment. It acts as a barrier against cold, heat, injuries, infections, chemicals, radiations or other exogeneous factors, and it is also known as the mirror of the soul. The skin is involved in body temperature regulation by the storage of fat and water. It is an interesting tissue in regard to the local and transdermal application of active ingredients for prevention or treatment of pathological conditions. Topical and transdermal delivery is an emerging route of drug and cosmetic administration. It is beneficial for avoiding side effects and rapid metabolism. Many pharmaceutical, technological and cosmetic innovations have been described and patented recently in the field. In this review, the main features of skin morphology and physiology are presented and are being followed by the description of classical and novel nanoparticulate dermal and transdermal drug formulations. The biophysical aspects of the penetration of drugs and cosmetics into or across the dermal barrier and their investigation in diffusion chambers, skin-on-a-chip devices, high-throughput measuring systems or with advanced analytical techniques are also shown. The current knowledge about mathematical modeling of skin penetration and the future perspectives are briefly discussed in the end, all also involving nanoparticulated systems. Full article

(This article belongs to the Special Issue Nanoparticles for Local Drug Delivery)

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44 pages, 2418 KiB

Open AccessEditor’s ChoiceReview

Recent Approaches for the Topical Treatment of Psoriasis Using Nanoparticles

by Krisztina Bodnár, Pálma Fehér, Zoltán Ujhelyi, Ildikó Bácskay and Liza Józsa

Pharmaceutics 2024, 16(4), 449; https://doi.org/10.3390/pharmaceutics16040449 - 25 Mar 2024

Cited by 14 | Viewed by 7768

Abstract

Psoriasis (PSO) is a chronic autoimmune skin condition characterized by the rapid and excessive growth of skin cells, which leads to the formation of thick, red, and scaly patches on the surface of the skin. These patches can be itchy and painful, and they may cause discomfort for patients affected by this condition. Therapies for psoriasis aim to alleviate symptoms, reduce inflammation, and slow down the excessive skin cell growth. Conventional topical treatment options are non-specific, have low efficacy and are associated with adverse effects, which is why researchers are investigating different delivery mechanisms. A novel approach to drug delivery using nanoparticles (NPs) shows promise in reducing toxicity and improving therapeutic efficacy. The unique properties of NPs, such as their small size and large surface area, make them attractive for targeted drug delivery, enhanced drug stability, and controlled release. In the context of PSO, NPs can be designed to deliver active ingredients with anti-inflammatory effect, immunosuppressants, or other therapeutic compounds directly to affected skin areas. These novel formulations offer improved access to the epidermis and facilitate better absorption, thus enhancing the therapeutic efficacy of conventional anti-psoriatic drugs. NPs increase the surface-to-volume ratio, resulting in enhanced penetration through the skin, including intracellular, intercellular, and trans-appendage routes. The present review aims to discuss the latest approaches for the topical therapy of PSO using NPs. It is intended to summarize the results of the in vitro and in vivo examinations carried out in the last few years regarding the effectiveness and safety of nanoparticles. Full article

(This article belongs to the Special Issue Nanoparticles for Local Drug Delivery)

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