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Particle Engineering for Drug Delivery Applications

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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 (10 December 2021) | Viewed by 31994

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Dr. Samantha Meenach

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Guest Editor

Particle Engineering Laboratory, College of Engineering, University of Rhode Island, Kingston, RI 02881, USA
Interests: particle engineering; drug delivery; tissue engineering; nanocomposite microparticles; pulmonary drug delivery
Special Issues, Collections and Topics in MDPI journals

Dr. Jie Shen

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Guest Editor

Department of Pharmaceutical Sciences, Bouvé College of Health Sciences, Northeastern University, Boston, MA 02115, USA
Interests: nanoparticle-based drug delivery systems; long acting parenterals; topical dosage forms; in vitro dissolution testing; in vitro and in vivo correlation; quality control
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Particle engineering has been increasingly used to prepare active pharmaceutical ingredients (APIs) for drug product formulation and drug delivery applications, for oral solid and inhaled particle formulations. The production and performance of such formulations can be greatly impacted by the given excipients and APIs, in addition to interactions between these components. Particle engineering results in the controlled production of drug particles with optimized size, morphology, and structure, using a wide variety of formulation and post-processing techniques. Potential goals for these techniques include narrow particle size distribution, improved dispersibility, enhanced stability and bioavailability, sustained release, or specific targeting. As a result, many drug delivery formulations utilize particle engineering technology. While particle engineering has been used to increase bioavailability in oral solid dose medications, it can be translated into a variety of applications, including intravenous nanoparticles, topical particle formulations, aerosol particle formulations, etc. The aim of this Special Issue is to highlight recent advances in particle engineering applications, in relation to pharmaceutical-based particle systems. Particle-based systems that investigate a variety of formulation and/or processing parameters and their impact on the particle properties will be considered. Moreover, scientific approaches related to design of fit, particle formation, structure and functional performance are welcome, including experimental and theoretical or modelling approaches.

Dr. Samantha Meenach
Dr. Jie Shen
Guest Editors

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Keywords

Particle engineering
Drug delivery applications
Particle formulations
Engineering microparticles and nanoparticles
Advanced manufacturing technologies
Design of experiment

Published Papers (9 papers)

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Research

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17 pages, 3389 KiB

Open AccessArticle

Formulation and Efficacy of Catalase-Loaded Nanoparticles for the Treatment of Neonatal Hypoxic-Ischemic Encephalopathy

by Andrea Joseph, Chris W. Nyambura, Danielle Bondurant, Kylie Corry, Denise Beebout, Thomas R. Wood, Jim Pfaendtner and Elizabeth Nance

Pharmaceutics 2021, 13(8), 1131; https://doi.org/10.3390/pharmaceutics13081131 - 23 Jul 2021

Cited by 6 | Viewed by 3563

Abstract

Neonatal hypoxic-ischemic encephalopathy is the leading cause of permanent brain injury in term newborns and currently has no cure. Catalase, an antioxidant enzyme, is a promising therapeutic due to its ability to scavenge toxic reactive oxygen species and improve tissue oxygen status. However, upon in vivo administration, catalase is subject to a short half-life, rapid proteolytic degradation, immunogenicity, and an inability to penetrate the brain. Polymeric nanoparticles can improve pharmacokinetic properties of therapeutic cargo, although encapsulation of large proteins has been challenging. In this paper, we investigated hydrophobic ion pairing as a technique for increasing the hydrophobicity of catalase and driving its subsequent loading into a poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) nanoparticle. We found improved formation of catalase-hydrophobic ion complexes with dextran sulfate (DS) compared to sodium dodecyl sulfate (SDS) or taurocholic acid (TA). Molecular dynamics simulations in a model system demonstrated retention of native protein structure after complexation with DS, but not SDS or TA. Using DS-catalase complexes, we developed catalase-loaded PLGA-PEG nanoparticles and evaluated their efficacy in the Vannucci model of unilateral hypoxic-ischemic brain injury in postnatal day 10 rats. Catalase-loaded nanoparticles retained enzymatic activity for at least 24 h in serum-like conditions, distributed through injured brain tissue, and delivered a significant neuroprotective effect compared to saline and blank nanoparticle controls. These results encourage further investigation of catalase and PLGA-PEG nanoparticle-mediated drug delivery for the treatment of neonatal brain injury. Full article

(This article belongs to the Special Issue Particle Engineering for Drug Delivery Applications)

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12 pages, 1455 KiB

Open AccessArticle

Targeted Liposomes Encapsulating miR-603 Complexes Enhance Radiation Sensitivity of Patient-Derived Glioblastoma Stem-Like Cells

by Ahmed M. Shabana, Beibei Xu, Zachary Schneiderman, Jun Ma, Clark C. Chen and Efrosini Kokkoli

Pharmaceutics 2021, 13(8), 1115; https://doi.org/10.3390/pharmaceutics13081115 - 21 Jul 2021

Cited by 13 | Viewed by 2553

Abstract

Despite potential for clinical efficacy, therapeutic delivery of microRNAs (miRNA) remains a major translational barrier. Here, we explore a strategy for miRNA delivery in the treatment of glioblastoma, the most common form of adult brain cancer, that involves complexation of miRNA with polyethylenimine (PEI) and encapsulation in targeted liposomes. miRNA 603 (miR-603) is a master regulatory miRNA that suppresses glioblastoma radiation resistance through down-regulation of insulin-like growth factor 1 (IGF1) signaling. miR-603 was complexed with PEI, a cationic polymer, and encapsulated into liposomes decorated with polyethylene glycol (PEG) and PR_b, a fibronectin-mimetic peptide that specifically targets the α₅β₁ integrin that is overexpressed in glioblastomas. Cultured patient-derived glioblastoma cells internalized PR_b-functionalized liposomes but not the non-targeted liposomes. The integrin targeting and complexation of the miRNA with PEI were associated with a 22-fold increase in intracellular miR-603 levels, and corresponding decreases in IGF1 and IGF1 receptor (IGF1R) mRNA expression. Moreover, treatment of glioblastoma cells with the PR_b liposomes encapsulating miR-603/PEI sensitized the cells to ionizing radiation (IR), a standard of care treatment for glioblastomas. These results suggest that PR_b-functionalized PEGylated liposomes encapsulating miR-603/PEI complexes hold promise as a therapeutic platform for glioblastomas. Full article

(This article belongs to the Special Issue Particle Engineering for Drug Delivery Applications)

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15 pages, 8742 KiB

Open AccessArticle

Effect of Storage Humidity on Physical Stability of Spray-Dried Naproxen Amorphous Solid Dispersions with Polyvinylpyrrolidone: Two Fluid Nozzle vs. Three Fluid Nozzle

by Sonal V. Bhujbal, Yongchao Su, Vaibhav Pathak, Dmitry Y. Zemlyanov, Alex-Anthony Cavallaro, Eric J. Munson, Lynne S. Taylor and Qi (Tony) Zhou

Pharmaceutics 2021, 13(7), 1074; https://doi.org/10.3390/pharmaceutics13071074 - 13 Jul 2021

Cited by 5 | Viewed by 3901

Abstract

In a spray drying operation, a two-fluid nozzle (2FN) with a single channel is commonly used for atomizing the feed solution. However, the less commonly used three-fluid nozzle (3FN) has two separate channels, which allow spray drying of materials in two incompatible solution systems. Although amorphous solid dispersions (ASDs) prepared using a 3FN have been reported to deliver comparable drug dissolution performance relative to those prepared using a 2FN, few studies have systematically examined the effect of 3FN on the physical stability. Therefore, the goal of this work is to systematically study the physical stability of ASDs that are spray-dried using a 3FN compared to those prepared using the traditional 2FN. For the 2FN, a single solution of naproxen and polyvinylpyrrolidone (PVP) was prepared in a mixture of acetone and water at a 1:1 volume ratio because 2FN allows for only one solution inlet. For the 3FN, naproxen and PVP were dissolved individually in acetone and water, respectively, because 3FN allows simultaneous entry of two solutions. Upon storage of the formulated ASDs at different humidity levels (25%, 55% and 75% RH), naproxen crystallized more quickly from the 3FN ASDs as compared with the 2FN ASDs. 3FN ASDs crystallized after 5 days of storage at all conditions, whereas 2FN ASDs did not crystallize even at 55% RH for two months. This relatively higher crystallization tendency of 3FN ASDs was attributed to the inhomogeneity of drug and polymers as identified by the solid-state Nuclear Magnetic Resonance findings, specifically due to poor mixing of water- and acetone-based solutions at the 3FN nozzle. When only acetone was used as a solvent to prepare drug-polymer solutions for 3FN, the formulated ASD was found to be stable for >3 months of storage (at 75% RH), which suggests that instability of the 3FN ASD was due to the insufficient mixing of water and acetone solutions. This study provides insights into the effects of solvent and nozzle choices on the physical stability of spray-dried ASDs. Full article

(This article belongs to the Special Issue Particle Engineering for Drug Delivery Applications)

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13 pages, 1271 KiB

Open AccessArticle

Liqui-Mass Technology as a Novel Tool to Produce Sustained Release Liqui-Tablet Made from Liqui-Pellets

by Matthew Lam, Nour Nashed and Ali Nokhodchi

Pharmaceutics 2021, 13(7), 1049; https://doi.org/10.3390/pharmaceutics13071049 - 09 Jul 2021

Cited by 4 | Viewed by 3203

Abstract

The Liqui-Mass technology (also known as Liqui-Pellet technology) has shown promising results in terms of enhancing the drug release rate of water insoluble drugs in a simplistic approach. However, there is no current study on sustained-release formulation using the Liqui-Mass technology. In this study, an attempt was made to produce a sustained-release Liqui-Tablet for the first time using a matrix-based approach. The non-volatile co-solvent used in the investigation included Tween 80, Tween 20 and Kolliphor EL. The production of sustained-release propranolol hydrochloride Liqui-Tablet was successful, and data from the saturation solubility test and dissolution test did not show much difference among the mentioned non-volatile co-solvent. The best Liqui-Tablet formulation took 24 h for drug release to reach at around 100%. There seemed to be a synergistic retarding drug release effect when a non-volatile co-solvent and Eudragit RS PO were used together. The increase of Eudragit RS PO concentration increased the retardant effect. Kinetic drug release analysis suggests that the best formulation followed the Higuchi model. The flowability of pre-compressed Liqui-Tablet pellets had no issues and its size distribution was narrow. Liqui-Tablet was generally robust and most formulations passed the friability test. The study revealed that Liqui-Mass technology can be employed to sustain drug release. Full article

(This article belongs to the Special Issue Particle Engineering for Drug Delivery Applications)

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12 pages, 2811 KiB

Open AccessArticle

Hierarchical Particle Approach for Co-Precipitated Amorphous Solid Dispersions for Use in Preclinical In Vivo Studies

by Luke Schenck, Christopher Boyce, Derek Frank, Sampada Koranne, Heidi M. Ferguson and Neil Strotman

Pharmaceutics 2021, 13(7), 1034; https://doi.org/10.3390/pharmaceutics13071034 - 07 Jul 2021

Cited by 12 | Viewed by 3342

Abstract

Amorphous solid dispersions (ASD) have become a well-established strategy to improve exposure for compounds with insufficient aqueous solubility. Of methods to generate ASDs, spray drying is a leading route due to its relative simplicity, availability of equipment, and commercial scale capacity. However, the broader industry adoption of spray drying has revealed potential limitations, including the inability to process compounds with low solubility in volatile solvents, inconsistent molecular uniformity of spray dried amorphous dispersions, variable physical properties across batches and scales, and challenges containing potent compounds. In contrast, generating ASDs via co-precipitation to yield co-precipitated amorphous dispersions (cPAD) offers solutions to many of those challenges and has been shown to achieve ASDs comparable to those manufactured via spray drying. This manuscript applies co-precipitation for early safety studies, developing a streamlined process to achieve material suitable for dosing as a suspension in conventional toxicity studies. Development targets involved achieving a rapid, safely contained process for generating ASDs with high recovery yields. Furthermore, a hierarchical particle approach was used to generate composite particles where the cPAD material is incorporated in a matrix of water-soluble excipients to allow for rapid re-dispersibility in the safety study vehicle to achieve a uniform suspension for consistent dosing. Adopting such an approach yielded a co-precipitated amorphous dispersion with comparable stability, thermal properties, and in vivo pharmacokinetics to spray dried amorphous materials of the same composition. Full article

(This article belongs to the Special Issue Particle Engineering for Drug Delivery Applications)

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12 pages, 7025 KiB

Open AccessArticle

Designing of Co_0.5Ni_0.5Ga_xFe_2−xO₄ (0.0 ≤ x ≤ 1.0) Microspheres via Hydrothermal Approach and Their Selective Inhibition on the Growth of Cancerous and Fungal Cells

by Suriya Rehman, Munirah A. Almessiere, Suhailah S. Al-Jameel, Uzma Ali, Yassine Slimani, Nedaa Tashkandi, Najat S. Al-Saleh, Ayyar Manikandan, Firdos Alam Khan, Ebtesam A. Al-Suhaimi and Abdulhadi Baykal

Pharmaceutics 2021, 13(7), 962; https://doi.org/10.3390/pharmaceutics13070962 - 26 Jun 2021

Cited by 13 | Viewed by 1861

Abstract

The current study offers an efficient design of novel nanoparticle microspheres (MCs) using a hydrothermal approach. The Co_0.5Ni_0.5Ga_xFe_2−xO₄ (0.0 ≤ x ≤ 1.0) MCs were prepared by engineering the elements, such as cobalt (Co), nickel (Ni), iron (Fe), and gallium (Ga). There was a significant variation in MCs’ physical structure and surface morphology, which was evaluated using energy dispersive X-ray analysis (EDX), X-ray diffractometer (XRD), high-resolution transmission electron microscopy (HR-TEM), and scanning electron microscope (SEM). The anti-proliferative activity of MCs was examined by MTT assay and DAPI staining using human colorectal carcinoma cells (HCT-116), human cervical cancer cells (HeLa), and a non-cancerous cell line—human embryonic kidney cells (HEK-293). Post 72 h treatment, MCs caused a dose dependent inhibition of growth and proliferation of HCT-116 and HeLa cells. Conversely, no cytotoxic effect was observed on HEK-293 cells. The anti-fungal action was assessed by the colony forming units (CFU) technique and SEM, resulting in the survival rate of Candida albicans as 20%, with severe morphogenesis, on treatment with MCs x = 1.0. These findings suggest that newly engineered microspheres have the potential for pharmaceutical importance, in terms of infectious diseases and anti-cancer therapy. Full article

(This article belongs to the Special Issue Particle Engineering for Drug Delivery Applications)

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Review

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43 pages, 8443 KiB

Open AccessReview

Mesoporous Silica Particles as Drug Delivery Systems—The State of the Art in Loading Methods and the Recent Progress in Analytical Techniques for Monitoring These Processes

by Katarzyna Trzeciak, Agata Chotera-Ouda, Irena I. Bak-Sypien and Marek J. Potrzebowski

Pharmaceutics 2021, 13(7), 950; https://doi.org/10.3390/pharmaceutics13070950 - 24 Jun 2021

Cited by 71 | Viewed by 5858

Abstract

Conventional administration of drugs is limited by poor water solubility, low permeability, and mediocre targeting. Safe and effective delivery of drugs and therapeutic agents remains a challenge, especially for complex therapies, such as cancer treatment, pain management, heart failure medication, among several others. Thus, delivery systems designed to improve the pharmacokinetics of loaded molecules, and allowing controlled release and target specific delivery, have received considerable attention in recent years. The last two decades have seen a growing interest among scientists and the pharmaceutical industry in mesoporous silica nanoparticles (MSNs) as drug delivery systems (DDS). This interest is due to the unique physicochemical properties, including high loading capacity, excellent biocompatibility, and easy functionalization. In this review, we discuss the current state of the art related to the preparation of drug-loaded MSNs and their analysis, focusing on the newest advancements, and highlighting the advantages and disadvantages of different methods. Finally, we provide a concise outlook for the remaining challenges in the field. Full article

(This article belongs to the Special Issue Particle Engineering for Drug Delivery Applications)

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23 pages, 1252 KiB

Open AccessReview

Nanoparticles as a Tool in Neuro-Oncology Theranostics

by Andrea L. Klein, Grant Nugent, John Cavendish, Werner J. Geldenhuys, Krishnan Sriram, Dale Porter, Ross Fladeland, Paul R. Lockman and Jonathan H. Sherman

Pharmaceutics 2021, 13(7), 948; https://doi.org/10.3390/pharmaceutics13070948 - 24 Jun 2021

Cited by 3 | Viewed by 2582

Abstract

The rapid growth of nanotechnology and the development of novel nanomaterials with unique physicochemical characteristics provides potential for the utility of nanomaterials in theranostics, including neuroimaging, for identifying neurodegenerative changes or central nervous system malignancy. Here we present a systematic and thorough review of the current evidence pertaining to the imaging characteristics of various nanomaterials, their associated toxicity profiles, and mechanisms for enhancing tropism in an effort to demonstrate the utility of nanoparticles as an imaging tool in neuro-oncology. Particular attention is given to carbon-based and metal oxide nanoparticles and their theranostic utility in MRI, CT, photoacoustic imaging, PET imaging, fluorescent and NIR fluorescent imaging, and SPECT imaging. Full article

(This article belongs to the Special Issue Particle Engineering for Drug Delivery Applications)

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23 pages, 3500 KiB

Open AccessReview

Advances in Lipid-Based Nanoparticles for Cancer Chemoimmunotherapy

by Tianqi Wang, Yusuke Suita, Saradha Miriyala, Jordan Dean, Nikos Tapinos and Jie Shen

Pharmaceutics 2021, 13(4), 520; https://doi.org/10.3390/pharmaceutics13040520 - 09 Apr 2021

Cited by 25 | Viewed by 3654

Abstract

Nanomedicines have shown great potential in cancer therapy; in particular, the combination of chemotherapy and immunotherapy (namely chemoimmunotherapy) that is revolutionizing cancer treatment. Currently, most nanomedicines for chemoimmunotherapy are still in preclinical and clinical trials. Lipid-based nanoparticles, the most widely used nanomedicine platform in cancer therapy, is a promising delivery platform for chemoimmunotherapy. In this review, we introduce the commonly used immunotherapy agents and discuss the opportunities for chemoimmunotherapy mediated by lipid-based nanoparticles. We summarize the clinical trials involving lipid-based nanoparticles for chemoimmunotherapy. We also highlight different chemoimmunotherapy strategies based on lipid-based nanoparticles such as liposomes, nanodiscs, and lipid-based hybrid nanoparticles in preclinical research. Finally, we discuss the challenges that have hindered the clinical translation of lipid-based nanoparticles for chemoimmunotherapy, and their future perspectives. Full article

(This article belongs to the Special Issue Particle Engineering for Drug Delivery Applications)

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