Glossary: Nanoparticle Types, Applications & Characterization Parameters
August 2020 | By Dr. Natalia Sannikova, Senior Formulation Scientist at Ascension Sciences
Too often, there are misunderstandings and questioning of results across studies simply because terms are not being used in the same manner to describe the same process. Herein, the Ascension Sciences team has extracted commonly used terms to describe characterization parameters, and defined them in order to establish a baseline from which more detailed discussions can take place.
Biocompatibility
The quality of not having toxic or injurious effects on biological systems [1].
Colloid
A mixture in which one substance of microscopically dispersed insoluble particles is suspended throughout another substance [2].
Cytotoxicity
The quality of being toxic to cells. Cytotoxic compounds can result in loss of cell membrane integrity and rapid death (necrosis), prevent cells from actively growing and dividing (a decrease in cell viability) or activate a genetic program of controlled cell death (apoptosis) [3].
Emulsion
A mixture of two or more liquids that are normally immiscible (unmixable or unblendable); dispersions of oil in water (o/w) or water in oil (w/o).
Ethosomes
Phospholipid nanovesicles with a relative high concentration of ethanol (20-45%), glycols and water used for dermal and transdermal delivery of molecules [4]. They have high penetration of the outermost layer of the skin, which enhances the permeation of encapsulated drugs.
Isotropic mixture
A mixture that has uniform physical properties in every direction.
Lipid Nanoparticles (LNP)
See “Liposomes”.
Liposomes
Artificial nanosized vesicular structures consisting of an aqueous core surrounded with at least one phospholipid layer. The liposome can be used as a vehicle for administration of nutrients and pharmaceutical drugs [5]. Liposomes are classified based on their size and number of lipid bilayers:
- Small unilamellar vesicles (SUV) – 20 – 100 nm; one lipid bilayer
- Large unilamellar vesicles (LUV) – >100 nm; one lipid bilayer
- Multilamellar vesicles (MLV) – >100 nm; multiple lipid bilayers organized in an onion-like structure
- Multivesicular vesicles (MVV) – multiple lipid bilayers; one vesicle contains several smaller vesicles.
Pro’s
- Biocompatible & biodegradable
- Improved systemic exposure
- Possible targeted delivery
- Co-delivery of multiple APIs
- Low immunogenicity
- Protect drug against chemical degradation
Con’s
- Cytotoxicity
- Limited administration routes
- Quick uptake by reticuloendothelial system
- Low encapsulation efficiency
Micelle
A spherical aggregate of amphiphilic molecules in an aqueous solution with particle diameter 5 – 100 nm [6].
Pro’s
- High membrane permeability
- Improved solubility & systemic exposure
Con’s
- Insufficient sustained release
- Potential cytotoxicity due to high surfactant content
Microemulsion
Thermodynamically stable colloidal dispersion consisting of small spheroid particles (comprised of oil, surfactant, and possibly co-surfactant) dispersed within an aqueous medium) [7]. “Thermodynamically stable” here means liquids in the mixture will not become separated; energy of the microemulsion is lower than energies of its components and hence the microemulsion state is more favourable [8].
Nanoemulsion
Thermodynamically unstable transparent or translucent nanosized emulsion stabilized by surfactants having the droplet size 10–100 nm [7]. “Thermodynamically unstable” refers to the fact that liquids in the mixture will become separated eventually [8].
Pro’s
- Increased water-solubility and potency
- Biocompatible and biodegradable
- Ease of preparation
Con’s
- Limited protection against degradation in gastro-intestinal tract or blood stream
- Limited administration routes
Nanoparticle (NP)
Tiny materials with size ranges from 1 to 100 nm, nanoparticles are used to deliver drugs within the body in an analogous way to delivery trucks bringing packages to their recipients. Both are carrier vehicles for their payloads and are meant to protect their contents in order to reach the right destination, at the right time and in a safe manner. Carrier molecules are called excipients and the drug is often called the active pharmaceutical ingredient or API. Excipients are chosen and assembled to give specific properties to the particle such as timed release of the drug or targeted delivery to chosen tissue or cell types.
Furthermore, nanoparticles can provide protection to their APIs that might be sensitive to degradation due to the action of light, exposure to acidic or basic pH, temperature or oxidation over time.
Nanostructured Lipid Carriers (NLC)
Type of solid lipid nanoparticles; a formulation extension of SLNs in which the NLC lipid particle carrier matrix is composed of multiple lipids [9]. The most common type of NLC matrix is a mixture of a solid lipid with chemically different liquid lipids.
Pro’s
- High capacity of drug-loading as compared to SLNs
- Leakage of drug during storage is less than SLNs
Nanoparticle Size
When reported in literature or as a specification, nanoparticle size refers to the average diameter of the particles within the sample of interest. The particle population in a sample is comprised of a distribution of sizes as such, another metric called the polydispersity index (PDI) is often reported along with size.
Nanoparticle size has a number of implications on the performance of the formulation. Varying the size can affect the stability of the particles, the ability of the particles to move through tissues, and the amount of active ingredient contained and subsequently released.
Particle size is most often determined using dynamic light scattering (DLS) where a laser’s transmission and reflection through the sample are measured and then correlated to size. Direct diameters can be measured using transmission electron microscopy (TEM) where a picture of the particles is taken, and size is directly assessed. In both methods, an average size is reported.
Polydispersity Index (PDI)
PDI is used to estimate the average uniformity of a particle population, and larger PDI values correspond to a larger size distribution in the particle sample. PDI can also indicate nanoparticle aggregation along with the consistency and efficiency of particle surface modifications throughout the particle sample [10]. A sample is considered monodisperse when the PDI value is less than 0.1.
A monodisperse population is important in order to have consistent performance from the formulation. In a given formulation, if the PDI is high, the performance of the larger particles will vary from that of the smaller ones in terms of drug delivery, stability or other desired specifications. Although some of the particles might achieve the desired result, it is possible that the effect could be masked by off target or unwanted behaviour from the other particles.
Polymer Nanoparticles (PNP)
Colloidal particles of size range 10 nm – 1 μm and solid in nature. Depending on preparation method, polymeric nanoparticles can form two types of structures: nanosphere and nanocapsule. Nanospheres consist of a matrix system in which the drug is uniformly dispersed whereas in nanocapsules the drug is embedded in a cavity and the cavity is surrounded by a polymeric membrane [11].
Pro’s
- Stable drug release in vivo
- Increased retention time of drug
- Low immunogenicity
- Protect drug against chemical degradation
- Co-delivery of multiple APIs
Con’s
- Initial burst release of drug
- Required removal of non-degradable polymer
- Limit of administration routes
Potency
A measure of drug activity expressed in terms of the amount required to produce an effect of given intensity [12]. A highly potent drug evokes a given response at low concentrations, while a drug of lower potency evokes the same response only at higher concentrations.
Self-Emulsifying Drug Delivery Systems (SEDDS)
Mixtures of oils and surfactants, ideally isotropic, and sometimes containing cosolvents, which emulsify spontaneously to produce fine oil-in-water emulsions when introduced into aqueous phase under gentle agitation, for example in gastro-intestinal tract with mild agitation provided by gastric mobility [13].
Pro’s
- Improved absorption of lipophilic drugs
- Biodegradable and biocompatible
Con’s
- Drug precipitation
- Potential cytotoxicity due to high surfactant concentration
Surfactant
Surfactants are usually organic compounds that are amphiphilic, meaning they contain both hydrophobic groups (oil-soluble) and hydrophilic groups (water-soluble) [14].
Solid Lipid Nanoparticles (SLN)
Lipid nanoparticles are comprised of surfactant-stabilised lipids that are solid at both room and body temperature, typically formulated with a single high-purity lipid as a primary carrier material [15-19].
Pro’s
- Low toxicity
- Prolonged drug release
- Biocompatible and biodegradable
- Superior cellular uptake compared to liposomes and PNPs
- Ease of sterilization and scale up
- Protect drug against chemical degradation
Con’s
- Low space for drug encapsulation leading to poor drug loading capacity
- Chances of drug expulsion following polymeric transition during storage
- Interactions between drug and lipid matrix can affect encapsulation efficiency unpredictably
References
- Keong, L. C. & Halim, A. S. In Vitro Models in Biocompatibility Assessment for Biomedical-Grade Chitosan Derivatives in Wound Management. International Journal of Molecular Sciences 10, 1300–1313 (2009).
- Colloids & Gels. Instrumat Available at: https://instrumat.ch/application/colloids-gels/#:~:text=A colloid is a mixture,colloids with larger particle size.
- Elmore, S. Apoptosis: A Review of Programmed Cell Death. Toxicologic Pathology 35, 495–516 (2007).
- Natsheh, H. & Touitou, E. Phospholipid Vesicles for Dermal/Transdermal and Nasal Administration of Active Molecules: The Effect of Surfactants and Alcohols on the Fluidity of Their Lipid Bilayers and Penetration Enhancement Properties. Molecules 25, 2959 (2020).
- Bozzuto, G. & Molinari, A. Liposomes as nanomedical devices. International Journal of Nanomedicine 975 (2015). doi:10.2147/ijn.s68861
- Micelle. Micelle – an overview | ScienceDirect Topics Available at: https://www.sciencedirect.com/topics/immunology-and-microbiology/micelle.
- Anton, N. & Vandamme, T. F. Nano-emulsions and micro-emulsions: Clarifications of the critical differences. Pharm. Res. 28, 978–985 (2011).
- Mcclements, D. J. Nanoemulsions versus microemulsions: terminology, differences, and similarities. doi:10.1039/c2sm06903b
- Isalomboto Nkanga, C., Murhimalika Bapolisi, A., Ikemefuna Okafor, N. & Werner Maçedo Krause, R. General Perception of Liposomes: Formation, Manufacturing and Applications. in Liposomes – Advances and Perspectives [Working Title] (2019). doi:10.5772/intechopen.84255
- Danaei, M. et al. Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems. Pharmaceutics 10, 57 (2018).
- Singh, R. & Lillard, J. W. Nanoparticle-based targeted drug delivery. Experimental and Molecular Pathology 86, 215–223 (2009).
- Salahudeen, M. S. & Nishtala, P. S. An overview of pharmacodynamic modelling, ligand-binding approach and its application in clinical practice. Saudi Pharmaceutical Journal 25, 165–175 (2017).
- Ganesan, P. & Narayanasamy, D. Lipid nanoparticles: Different preparation techniques, characterization, hurdles, and strategies for the production of solid lipid nanoparticles and nanostructured lipid carriers for oral drug delivery. Sustainable Chemistry and Pharmacy (2017). doi:10.1016/j.scp.2017.07.002
- Nakama, Y. Surfactants. Cosmetic Science and Technology 231–244 (2017). doi:10.1016/b978-0-12-802005-0.00015-x
- Zanchetta, B., Chaud, M. V. & Santana, M. H. A. Self-Emulsifying Drug Delivery Systems (SEDDS) in Pharmaceutical Development. J Adv Chem Eng 5, 3 (2015).
- Pardeike, J., Hommoss, A. & Müller, R. H. Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. Int. J. Pharm. 366, 170–184 (2009).
- Mehnert, W. & Mäder, K. Solid lipid nanoparticles: Production, characterization and applications. Advanced Drug Delivery Reviews (2012). doi:10.1016/j.addr.2012.09.021
- Mishra, V. et al. Solid lipid nanoparticles: Emerging colloidal nano drug delivery systems. Pharmaceutics 10, 1–21 (2018).
- Clayton KN, Salameh JW, Wereley ST, Kinzer-Ursem TL. Physical characterization of nanoparticle size and surface modification using particle scattering diffusometry. Biomicrofluidics 2016 Sep 21;10(5):054107.
About ASI
Employing nanoparticle formulation technology from the cutting edge of genetic medicine, Ascension Sciences is developing cannabinoid nano delivery platforms and techniques for the pharma and nutraceutical industries. Liposomes, nanoemulsions, lipid nanoparticles and polymeric nanoparticles have all shown promise in improving the therapeutic benefits of cannabinoids, but the full potential of these therapies has not yet been unlocked.
Our R&D and formulation development services are an efficient option for research driven firms that require the advantages of nanoparticle delivery for their active ingredients. We work with other passionate researchers in the industry that share a common goal of improving the human condition and bringing novel therapies to those who need them most.
For more information, please visit: https://ascensionsciences.com/
