4.5 Article

Self-Assembled Hyaluronate/Protamine Polyelectrolyte Nanoplexes: Synthesis, Stability, Biocompatibility and Potential Use as Peptide Carriers

Journal

JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
Volume 10, Issue 12, Pages 3658-3673

Publisher

AMER SCIENTIFIC PUBLISHERS
DOI: 10.1166/jbn.2014.1878

Keywords

Hyaluronic Acid; Protamine; Calcitonin; Nanoparticles; Polyelectrolyte Complex; Caco 2-Cells

Funding

  1. Irish Drug Delivery Research Network
  2. National Development Plan [07/SRC/B1154]
  3. EU Structural Funds and Science Foundation Ireland
  4. Solid State Pharmaceutical Cluster
  5. Science Foundation Ireland [07/SRC/B1158]

Ask authors/readers for more resources

This work investigates a new type of polyelectrolyte complex nanocarrier composed of hyaluronic acid (HA) and protamine (PROT). Small (approximately 60 nm) and negatively charged nanoparticles (NPs) with a polydispersity index of less than 0.2 were obtained with properties that were dependent on the mixing ratio, concentration of polyelectrolytes and molecular weight of HA. Salmon calcitonin (sCT) was efficiently (up to 100%) associated with the NPs, and the drug loading (9.6-39% w/w) was notably high, possibly due to an interaction between HA and sCT. The NPs released similar to 70-80% of the sCT after 24 hours, with the estimated total amount of released sCT depending on the amount of HA and PROT present in the NPs. The isoelectric point of the NPs was close to pH 2, and the negative surface charge was maintained above this pH. The HA/PROT nanoplexes protected the sCT from enzymatic degradation and showed low toxicity to intestinal epithelial cells, and thus may be a promising oral delivery system for peptides.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Pharmacology & Pharmacy

Inhibition of celecoxib crystallization by mesoporous silica - Molecular dynamics studies leading to the discovery of the stabilization origin

Daniel Kramarczyk, Justyna Knapik-Kowalczuk, Wojciech Smolka, Maria Ferreira Monteiro, Lidia Tajber, Marian Paluch

Summary: This article investigates the effect of mesoporous silica on the physical stability and molecular dynamics of the amorphous form of Celecoxib. It has been found that mesoporous silica can slow down the recrystallization process of Celecoxib and the formation of a monomolecular drug layer on the silica's surface is associated with the observed inhibition of recrystallization.

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES (2022)

Article Chemistry, Multidisciplinary

Medicine Maker: An Outreach Activity for Pharmaceutical Manufacturing and Health Literacy

Martin McHugh, Sarah Hayes, Lidia Tajber, Laurie Ryan

Summary: Public engagement in medicine plays a crucial role in promoting population health management and literacy. However, current activities often have a narrow focus, only targeting specific patient groups, diseases, or drugs. Therefore, a broader approach is needed to improve the overall health literacy of the general public.

JOURNAL OF CHEMICAL EDUCATION (2022)

Article Chemistry, Multidisciplinary

Osmolality of Excipients for Parenteral Formulation Measured by Freezing Point Depression and Vapor Pressure - A Comparative Analysis

Mariana Hugo Silva, Sarah P. Hudson, Lidia Tajber, Matthieu Garin, Wenyu Dong, Tatsiana Khamiakova, Rene Holm

Summary: This study investigated the difference in methods to determine the osmolality in solutions of stabilizers used for long-acting injectable suspensions. The results showed that the osmolality increased with increasing concentration for all polymers and surfactants, regardless of the measuring method used. Different measurement methods yielded different osmolality values for PVPs, PEGs, and Na-CMC. The vapor pressure method may be more suitable when the formulations contain higher concentrations of excipients and/or thermosensitive excipients.

PHARMACEUTICAL RESEARCH (2023)

Editorial Material Chemistry, Multidisciplinary

Crystallizing the Role of Solid-State Form in Drug Delivery

Lynne S. Taylor, Doris E. Braun, Lidia Tajber, Jonathan W. Steed

CRYSTAL GROWTH & DESIGN (2022)

Article Medicine, Research & Experimental

Impact of the Dicarboxylic Acid Chain Length on Intermolecular Interactions with Lidocaine

Julija Zotova, Brendan Twamley, Lidia Tajber

Summary: Acid-base multicomponent systems are commonly used to fine-tune the physicochemical properties of active pharmaceutical ingredients. However, the nature of intermolecular interactions within these systems is not accurately predicted by current prediction tools. In this study, the effect of carbon backbone length and flexibility on the molecular recognition, crystallization, and thermal behavior of lidocaine (LID) and dicarboxylic acid mixtures was investigated. The formation of eutectic phases, hydrogen bonding between the reacting components, and possible formation of new phases stemming from partial ionization of the counterions were observed.

MOLECULAR PHARMACEUTICS (2022)

Editorial Material Medicine, Research & Experimental

Crystallizing the Role of Solid-State Form in Drug Delivery

Lynne S. Taylor, Doris E. Braun, Lidia Tajber, Jonathan W. Steed

MOLECULAR PHARMACEUTICS (2022)

Article Chemistry, Multidisciplinary

Impact of Excipients and Seeding on the Solid-State Form Transformation of Indomethacin during Liquid Antisolvent Precipitation

Mariana Hugo Silva, Ajay Kumar, Benjamin K. Hodnett, Lidia Tajber, Rene Holm, Sarah P. Hudson

Summary: This study describes a novel approach combining liquid antisolvent precipitation with seeding to obtain a stable form of indomethacin API and achieve the desired particle size distribution. The results show that excipients and seeds influence the rate of transformation of indomethacin, and the particle size distribution and timing of seed addition are critical for obtaining the desired solid-state form.

CRYSTAL GROWTH & DESIGN (2022)

Article Nanoscience & Nanotechnology

The Pharmacological Effects of Silver Nanoparticles Functionalized with Eptifibatide on Platelets and Endothelial Cells

Justyna Hajtuch, Eliza Iwicka, Anna Szczoczarz, Damian Flis, Elzbieta Megiel, Piotr Cieciorski, Marek Witold Radomski, Maria Jose Santos-Martinez, Iwona Inkielewicz-Stepniak

Summary: In this study, we synthesized eptifibatide-functionalized silver nanoparticles and evaluated their pharmacological activity on platelets and endothelial cells. The results showed that AgNPs-EPI exhibited anti-aggregatory activity by regulating platelet aggregation, blood coagulation, and endothelial cell activity, at concentrations lower than the free drug. These findings provide preliminary evidence that AgNPs can be used as an effective delivery platform for antiplatelet drugs.

INTERNATIONAL JOURNAL OF NANOMEDICINE (2022)

Article Pharmacology & Pharmacy

Levofloxacin in nanostructured lipid carriers: Preformulation and critical process parameters for a highly incorporated formulation

Viviane Lucia Beraldo-Araujo, Ana Flavia Siqueira Vicente, Marcelo van Vliet Lima, Anita Umerska, Eliana B. Souto, Lidia Tajber, Laura Oliveira-Nascimento

Summary: Preformulation studies play a crucial role in the successful development of nanoformulations, as they help identify the best excipients and understand drug-excipient compatibility and interactions. This study focused on the development of nanostructured lipid carriers (NLCs) for delivering the antibiotic levofloxacin (LV) and systematically evaluated the critical process parameters to establish a stable system with high drug entrapment efficiency (EE).

INTERNATIONAL JOURNAL OF PHARMACEUTICS (2022)

Article Chemistry, Physical

Nucleation kinetics-based solvent selection for the liquid antisolvent crystallization of a lipophilic intermediate

Snehashis Nandi, Luis Padrela, Lidia Tajber, Alain Collas

Summary: The fundamental understanding of solubility and nucleation kinetics is crucial for the development of liquid antisolvent crystallization (LASC) process. This study determined the solubility of intermediate A in different solvents and binary mixtures using a liquid chromatographic method. The selection of the optimum scale and mixing conditions for measuring the metastable zone width (MSZW) in nucleation kinetics was demonstrated to be important. The derived kinetic parameters and accurate solubility data can guide solvent selection for the generation of nanosuspensions in LASC.

JOURNAL OF MOLECULAR LIQUIDS (2023)

Article Chemistry, Multidisciplinary

Controlling the Polymorphism of Indomethacin with Poloxamer 407 in a Gas Antisolvent Crystallization Process

Fidel Mendez Canellas, Vivek Verma, Jacek Kujawski, Robert Geertman, Lidia Tajber, Luis Padrela

Summary: The effects of processing conditions on the polymorphism of indomethacin were studied, and it was found that consistent formation of the pure alpha polymorphic form was only achieved when poloxamer 407 was used as an additive. The GAS method combined with poloxamer 407 as a molecular additive allowed for full control over the polymorphic form of indomethacin, regardless of the processing conditions employed.

ACS OMEGA (2022)

Article Pharmacology & Pharmacy

Development of long-acting injectable suspensions by continuous antisolvent crystallization: An integrated bottom-up process

Snehashis Nandi, Luis Padrela, Lidia Tajber, Alain Collas

Summary: This study demonstrates the operational feasibility of generating and stabilizing long-acting injectable suspensions of a practically insoluble drug, itraconazole, using continuous liquid antisolvent crystallization and downstream processing. The optimized microchannel reactor-based bottom-up crystallization setup and selection of suitable solvent and stabilizer resulted in a stable suspension with desired particle size distribution and solid concentration.

INTERNATIONAL JOURNAL OF PHARMACEUTICS (2023)

Article Chemistry, Physical

Sorbitol-coated indomethacin and naproxen particles produced by supercritical CO2-assisted spray drying

Fidel Mendez Canellas, Robert Geertman, Lidia Tajber, Luis Padrela

Summary: Co-spraying of APIs with excipients using supercritical CO2-assisted spray drying (SASD) was investigated to address formulation challenges. Results showed that SASD yielded particles with sizes ranging from 0.4-7.6 μm, where naproxen crystalline Form 1 particles were embedded in an amorphous sorbitol matrix, while indomethacin-sorbitol mixtures exhibited partial crystallinity. Naproxen-sorbitol mixtures formed homogeneous microparticle suspensions upon contact with water, while indomethacin-sorbitol mixtures were not reconstitutable. The API-sorbitol interactions were studied in detail using thermal analysis and COSMO-RS modelling. Overall, this work provides a better understanding of co-spraying of APIs with excipients for the formulation of reconstitutable dried microparticles.

JOURNAL OF SUPERCRITICAL FLUIDS (2023)

Article Chemistry, Medicinal

Hot Melt Extrusion for Improving the Physicochemical Properties of Polydatin Derived from Polygoni cuspidati Extract; A Solution Recommended for Buccal Applications

Magdalena Paczkowska-Walendowska, Lidia Tajber, Andrzej Miklaszewski, Judyta Cielecka-Piontek

Summary: This study prepared solid dispersions containing polydatin-rich Polygoni cuspidati extract by hot melt extrusion, aiming to enhance the release of poorly water-soluble compounds. The formulation based on Kollidon (R) VA64 exhibited the best tabletability properties and mucoadhesive properties.

PHARMACEUTICALS (2023)

Article Medicine, Research & Experimental

Impact of the Dicarboxylic Acid Chain Length on Intermolecular Interactions with Lidocaine

Julija Zotova, Brendan Twamley, Lidia Tajber

Summary: Multicomponent systems consisting of acids and bases are commonly used to fine-tune the properties of pharmaceutical ingredients. However, current prediction tools are not always accurate in predicting the interactions within these systems. In this study, the authors investigated the effects of acid carbon backbone length and flexibility on the behavior of mixtures containing lidocaine and dicarboxylic acids. The results showed the formation of new phases and deviations from predicted eutectic melting points, indicating the complex nature of these systems. Additionally, the structure of a previously unknown form of tridecanedioic acid was determined.

MOLECULAR PHARMACEUTICS (2022)

No Data Available