The application of nanotechnology in drug delivery systems (DDS) has been researched widely and seen an advancement over the past three decades. Since the 1970s, nanoparticles (NP) were primarily utilised in vaccine deliveries and cancer chemotherapy. In more recent years, they have been found to be promising for broader applications such as in proteins and therapeutic gene delivery systems. To date, there have been only a handful of nanocarrier-loaded drugs commercialised into the pharmaceutical market. More research is thus needed to facilitate a breakthrough of these products into the current market. This mini-review mainly focuses on four types of commonly utilised organic nanocarriers including micelles, compact polymerics, solid-lipid nanoparticles and liposomal vesicles and discusses the progress and some challenges associated with these nanoparticles.
The pharmaceutical industry has constantly been evolving in terms of development strategies and base the delivery of their therapeutic agents on two pivotal factors: i) developing medicines to be as selective as possible to the site of action in the body ii) maintaining a constant reproducible right concentration of drug at the right place in the body that reduces dosage frequency (
Nanotechnology is a fairly newly established field in the era of science that engages multi-scientific disciplines including chemistry, biology, engineering and physical sciences (
A well-known lecture “
It is estimated that around 70% of newly discovered drugs are water insoluble and about 40% of the currently used oral immediate-release drugs are also water-insoluble (
Nanocarriers can be utilised to obtain the goal of securing optimal therapeutic effects whilst at the same time minimizing the unwanted side effects (
This mini-review focuses on mainly four types of organic nanocarriers including micelles, compact polymerics, solid-lipid nanoparticles (NP) and liposomal vesicles. This comprises of definitions, classifications, methodologies and evaluation techniques. There is also a special focus on how each component has evolved over the past three decades. Some of the challenges associated with earlier NPs are also discussed.
Since the development of mono-functioning nano-carriers the next generation was introduced as “multi-functional” nano-particulates. This is still a growing field that is being explored. The surface properties of nano-carriers control their function, hence by modifying the surface of carriers in a favourable fashion, one can make them possess simultaneous performances as the name “multi-function” suggests (
1, Conventional active pharmaceutical ingredient (API) loaded nanocarrier. 2, modified nanocarrier surface with targeting agents. 3, addition of magnetic particles into the nanocarrier to induce carrier response to the surrounding magnetic field. 4, attachment of long circulating polymers such as poly (ethylene glycol) (PEG) to enhance drug blood circulation time. 5, attachment of contrast agents for imaging applications. 6, enhancing the nanocarrier cell penetration by attaching cell penetrating peptides onto the surface. 7, complexing negatively charged DNA onto the positively charged surface of nanocarrier. 8, The combination of all 1-7 functions converged on a so called multifunctional nanocarrier (adapted from
Manipulating solids at the atomic level transforms the properties of bulk material (
Some of the reviewed literature accord the prefix “nano” (meaning dwarf) to any matter with the size of less than 100 nm in at least in one dimension (
Pharmaceutical nano-particles can be classified based on distinct categories depending on any of their chemical composition, morphology or their applications.
Classification of nanoparticles (NPs) (adapted from (a)
Micelles are nano-sized vectors that are capable of self-assembly when exposed to aqueous solutions (
Self-assembly of micelles in aqueous solution (adapted from
Structures of a number of nano-carriers in DDS (adapted from
Various types of drugs, mainly sparingly soluble anti-cancer medicines, proteins and genes can be loaded into the hydrophobic core of the amphiphilic block copolymer (
Forster Resonance Ene.g., Transfer Technique (FRET) is an effective technique used to study the stability of polymeric micelles (
Polymeric micelles demonstrate an enhanced drug biodistribution preceded by an increase in the bioavailability of a drug across physiological barriers (
Polymeric nano-carriers (PNCs) are either synthetically or naturally sourced colloidal particles with widespread applications in drug delivery systems (DDS). Examples of naturally existent polymers are protein-based polymers including gelatine, collagen and albumin, or polysaccharides e.g., alginate, chitosan, agarose and hyaluronic acid (HA) (
Structures of a number of synthetic and natural polymers in DDS.
PNCs can be subdivided into two types based on their preparation methodologies: i) nanospheres ii) nanocapsules. Nanospheres are composed of solid matrix that is solid in its total mass (
On the other hand, nanocapsules bearing a vesicular-like structure such as a reservoir containing liquid (oil or water) or semisolid materials in the core that is surrounded by a solid polymeric shell (
From the synthetic polymers utilised in DDS, the most commonly used are saturated poly (α -hydroxy esters) such as poly (glycolic acid) (PGA), poly (lactic acid) (PLA) and poly (lactic-co-glycolic acid) (PLGA) copolymers (
The aforementioned polymers in
For instance, it is worth considering that how stereochemical centre in poly (lactic acid) (PLA) and poly (D, L-lactic-co-glycolic acid) (PLGA) affect polymer degradation rate following the rate of drug liberation.
The asymmetric α-carbon in PLA have laevorotatory (PLLA) and dextrorotatory (PDLA) enantiomers i.e., if all the stereocentres of PLA are L figured is termed PLLA (
There are several ways to categorise PNCs preparation techniques with various terminologies. A number of reviewed papers describe methodologies as i) top-down approach (e.g. media milling, high-pressure homogenisation and lithography), ii) bottom-up approach (e.g. self-assembly and chemical synthesis of nanoparticles) (
The particles size, morphology and polydispersity can be observed by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and photon correlation spectroscopy (PCS) known as dynamic light scattering (DLS) (
The nanoparticles surface charge that is articulated as zeta-potential (ζ) in colloidal research, is commonly measured by a Zetasizer instrument (
In the following, a brief description is given to aid the understanding behind the principles of zeta potential and its importance.
Surface charge of NPs is one of the important factors that has direct effects over toxicity and the extent of cellular uptake of nanoparticles causing their intended biological activity (
The potential of the actual particle surface that is termed Nernst (ψ0) potential is not measurable (
Generally, electrophoretic light scattering is a common method in zeta potential instruments.
From this technique, particles velocity is obtained while applying an electric field and that value is then used to calculate zeta potential through several mathematical equations (
Early research reported that nanoparticle concentration at low levels could directly affect the reproducibility and reliability of data sets obtained from zeta-potential and DLS (for particle size measurements) which can be particularly concerning for those studying NP’s toxicity (
Toxicological experiments are often carried out in small NPs’ concentrations on cell models in order to determine the extents of cytotoxicity effects (
A study concluded that the concentration effects of NPs on zeta-potential and DLS data reproducibility was not the case within a concentration range predicated based upon the nature of the sample in question (
Solid lipid nanocarriers (SLNs) are the first series of formulated lipid-based nanocarriers (
One of the main concerns in the earlier use of lipid particles as nanocarriers was their suitability as prolonged drug release devices in DDS (
There are three models used to incorporate APIs into SLNs (
(a) homogeneous matrix, (b) API-free core and drug-enriched shell, (c) 4 drug-enriched core (adapted from
Liposomes are spherical vesicles composed of amphiphilic bilayered phospholipids that re-arrange themselves in aqueous milieu (
A pictorial representation of types of liposomal surface modification (adapted from
The preparation methods of drug loading into liposomal systems fall into two types of techniques: i) passive loading techniques ii) active loading techniques, that each divide into further types of methods and is extensively covered in (
Over the past years, there have been several successfully marketed nanoparticulate formulations, in particular, liposomal-associated medicines that exhibit superior therapeutic profiles compared to that of their conventional formulations. Nevertheless, the controversial reports on the toxicity aspects of these formulations in literature suggest that further investigations in this field are warranted.
The intravenously administered antibiotic amphotericin B (AB) is often employed as the second or third line of treatment for the vector-born leishmaniasis disease (
However,
In chemotherapy, the anthracycline drug classes such as doxorubicin and daunorubicin have been the first line of effective treatment in broad use for many cancers since the early 1960s (
PEGylated liposomal doxorubicin (PLD) including Doxil® and Caelyx® have also been shown to greatly increase the drug circulation time as a result from the enhanced stability of the drug-loaded liposomal complex (
Nanotechnology has obtained gargantuan volume of researches and developments over the past three decades. A search on PubMed.gov shows around 1, 351 articles published over the applications of nanomedicines in DDS only in 2020. Despite the enormous experimental results from
(
The authors are grateful to the University of Huddersfield.
The authors note no conflicts of interest.