Nanostructured lipid carriers as a drug delivery system: A comprehensive review with therapeutic applications

Abstract

Recent advances in nanotechnology have enabled significant developments in health through innovative drug delivery systems. Nanostructured lipid carriers (NLCs) have emerged as a key technology in this field, offering enhanced drug stability, improved loading capacity, and reduced drug leakage compared to traditional solid lipid nanoparticles (SLNs). NLCs, such as ARM-NLC and PIO-loaded NLCs are specifically designed to optimize drug delivery and efficacy. Unlike other nanocarriers, NLCs provide controlled release and targeted delivery, making them highly effective for treating a range of diseases. Their applications include the treatment of skin cancer, Parkinson’s disease, Alzheimer’s disease, and breast cancer. The use of surface-engineered nanolayer coatings in NLCs has demonstrated significant improvements in targeting and delivering medications and bioactive substances to infection sites. Both in vitro and in vivo studies have shown promising results regarding the safety and efficacy of these NLC-based drug delivery systems.

Introduction

Nanotechnology is used in many fields, including environmental science, medicine, cosmetics, and nutraceutical research [1]. Nanotechnology has become a powerful tool in recent years for tackling the limitations of traditional drug delivery methods [2]. Nanocarriers are colloidal systems with an average diameter of less than 1 micron [3]. Since they have special qualities, such as a high surface-to-volume ratio and nanoscale size, nanoparticles can be employed for medicinal purposes [4]. Their decreased size compared to biological macromolecular medicines or standard chemotherapeutic agents allows them to be coupled with several support components and pharmaceutically active chemicals [5]. These components enable stimulus-based activation, imaging, targeting, and degradation resistance. However, the body processes nanoparticles differently than it does conventional medications [6].

Nanoparticles have distinct biodistribution profiles and hydrodynamic characteristics. It is noteworthy that interactions occurring at the nanobiological level have the potential to be used for better drug delivery [7]. The encapsulating moieties of nanocarriers can be altered to improve their pharmacokinetic and biodistribution characteristics, decrease toxicity, regulate release, improve solubility and stability, and deliver their payload to targeted sites [8]. The physiochemical characteristics of nanocarriers, such as their surface, composition, and shape, can be altered to improve their activities with fewer side effects. Nanostructured lipid carriers (NLCs) present promising advancements in drug delivery systems, yet they face several challenges that hinder their clinical application. These challenges include formulation complexities, stability issues, and biological barriers [9].Polymeric, lipidic, inorganic nanoparticles, liposomes, nanotubes, nanocomplexes, niosomes, and several other forms are examples of nanocarriers (figure 1) [10].

Nanocarriers’ surface characteristics have a major impact on their bioavailability, stability, cellular absorption, and biodistribution [11]. The surface charge expressed by the zeta potential influences the aggregation tendencies of the nanocarrier units, suggests potential electrostatic interactions between them, and helps in the selection of suitable coating materials [12]. There are several biological aspects that are influenced by the shape and aggregation behavior of nanocarriers, such as their half-life, targeting effectiveness, and toxicity [13]. Numerous non-spherical shapes, such as cubes, cones, hemispheres, cylinders, and other complex shapes, have a significant impact on those biological functions [14]. Triglycerides, partial glycerides, fatty acids, and waxes are the constituents of lipid nanoparticles, which are combined with various surfactant combinations [15]. Lipid nanoparticles exhibit effective and targeted drug delivery since their particle size is typically less than 1 μm [16]. Polymer nanoparticles, made of biodegradable and biocompatible polymers, are used in the synthesis of nanosized carriers [17]. Due to their capacity to carry large amounts of pharmaceuticals and to release drugs slowly while preventing their deterioration, their biodegradable nature has drawn much attention as potentially appropriate systems for drug administration [18]. Drug adsorption efficiency and surface quality are enhanced by the introduction of polymer nanoparticles [19].

Polymeric micelles are self-assembling block copolymer carriers made up of a core-shell structure. The essential micelle concentration of polymeric micelles, as well as their size and form, may be controlled by the structural and physical properties of copolymers [20]. The inorganic nanocarriers are gold nanoparticles, carbon nanotubes, quantum dots, mesoporous silicon, and magnetic nanocarriers. Inorganic nanocarriers are used for novel purposes such as cell labeling, imaging, biosensing, targeting, and diagnosis [21].

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Table 2. NLC for the management of different diseases

Drug	Excipient	Conclusion
Ribociclib	Labrafil, Labrasol, Campritol, Precirol, Gellucire, Stearic acid, Apifil, and Glycerol monostearate, Poloxamer and CremophorSpan-20, Span-60, Tween-20 and Tween-80	The NLCs were able to release RCB under control for up to 24 hours. Ex-vivo experiments shown a considerable increase in the skin's ability to retain the material compared to a conventional gel formulation. The encapsulation of RCB into NLCs appears to be a promising technique for the management of skin cancer.
Silymarin	Sefsol 218, Geleol, ethanol, Cremophor RH40, bile salt, carbopol 934, triethanolamine	Topically applied silymarin in the form of NLC gel significantly improves its capacity to protect skin from UVB-induced damage. The anticancer study's findings, which used an albino mouse skin cancer model as a paradigm, showed that animals given silymarin-NLC gel had superior tumor burden prevention.
5-fluorouracil and Resveratrol	Labrasol, emulcire™ 61 WL 2659, Tween® 80, methanol, ethanol, acetonitrile, Carbopol 934, polyethylene glycol-400, triethanolamine	Exhibited better penetration profile and higher drug entrapment than the conventional formulation. Higher flux and permeability coefficient of optimized formulation demonstrated that the lipid-nanosystem crossed the barrier and reached into the epidermis and dermis layer of skin. The linogel exceeded the conventional formulation in an in vitro effectiveness testing, exhibiting the lowest IC50 on the A431 cell line.
Docetaxel and Lidocaine	Myristyl myristate, Miglyol 812, chitosan, xanthan	Physical, biochemical, and histological metrics all demonstrated no adverse reactions from treatment with the hybrid hydrogel. A viable and alternative biocompatible formulation for the treatment of melanoma could involve docetaxel loaded by NLC combined with lidocaine-in-hydrogel.
Quercetin and Resveratrol	Labrafil M 2125, Labrafil M 2130, Cremophor RH40, Carbopol 934, triethanolamine	Through their distinct molecular mechanisms of action, quercetin and resveratrol show synergistic effect and overcome drawbacks associated with using single medicines to treat skin cancer.
Topotecan	Stearic acid, oleic acid, lecithin, taurodeoxycholate, trehalose, chitosan, acetic acid, triethanolamine	In comparison to their respective formulations containing unloaded TPT, hydrogels containing TPT-NLC considerably enhanced skin permeability. Lower dosages of TPT were used to increase cytotoxicity in vitro against melanoma cells (the IC50 of TPT-NLC is lower than the IC50 of TPT).
Donepezil and Embelin	Stearic acid, Oleic acid, Black seed oil, Castor oil, Tween 80, Tween 20 Compritol 888 ATO, Precirol ATO5, Gelucire, Geleole, Thymoquinone, Capryol 90, Cremophore, Poloxamer 407	Cell line research established a synergistic approach to drug combination. Ex vivo permeation showed that improved NLCs more effectively penetrated the goat nasal mucosa. The developed DPL and EMB-loaded NLC showed promising qualities and could be applied to intranasal AD treatment.
Pioglitazone	Tripalmitin, MCM, tween 80, pluronic F68, methanol, acetonitrile and ammonium acetate, Dimethyl sulphoxide	It was discovered that the formulation considerably increased PIO's permeability into the nasal mucosa. The safety of the produced formulation for in vivo administration has been established by a toxicity investigation. The IN-NLC showed direct nasal to brain drug transport, which greatly increased the medication's in vivo brain concentration. The current experiment illustrated the usefulness of IN-NLC for reusing PIO in AD management.
Curcumin	cetyl palmitate, Tween®80, Cholesterol	The effectiveness of curcumin's neuroprotective effects on an animal model of AD was examined, with a focus on its restricted size distribution (<120 nm) and high entrapment efficiency. Cur-NLC treatment of AD rats reduced the amount of amyloid plaques, thereby improving the disease's symptoms.
Astaxanthin	Glyceryl palmitostearate, Poloxamer 188, Polysorbate 80, oleic acid, Methanol,	AST-NLCs delivered via nose-brain delivery to AD-like rats demonstrated anti-amyloidogenic, anti-cholinesterase, antioxidant, anti-neuroinflammatory, and anti-apoptotic effects.
Entacapone	Glycerol monostearate, Oleic acid, and Tween 80, Hydrogenated palm oil, Olive oil, ethanol, methanol, and trimethylamine	Orally administered Entacapone NLCs improved the AUC in the plasma drug concentration profile, indicating improved bioavailability. The nanoscale particle size, improved solubilization, inhibition of extensive metabolism, and increased efficiency, help in dosage reduction and improve overall therapy.
Ropinirole	Propylene glycol monocaprylate, tripalmitin, polyoxyethylene sorbitan monolaurate, EDTA, Poloxamer 188	In comparison to control formulations, PK tests revealed 2.1 and 2.7-fold increases from oral administration of RP-SLN and RP-NLC, and 3.0 and 3.3-fold enhancements from topical administration of RP-SLN-C and RP-NLC-C.
Selegiline	Stearylamine, tween 80, olive oil, Pluronic F68	The produced formulation was found to have good loading capacity and entrapment efficiency. Using a nasal delivery system to provide a selegiline HCl-loaded nanolipid carrier may have benefits for Parkinson's disease treatment.
Idebenone	Precirol ATO 5, Miglyol 840, methanol and 2-propanol, Tween 80 and Labrasol	IDE NLCs increase the drug's bioavailability by 4.6 times in plasma and 2.8 times in the brain compartment compared to ordinary drug-loaded aqueous dispersions. IDE lipid-based nanostructured carrier system evidenced the potential for drug delivery and transport to brain over the conventional formulations.
Kaempferol	Compritol, Miglyol, poloxamer, chitosan oligosaccharides	An adjuvant paclitaxel co-therapy with kaempferol-loaded NLCs can result in a more effective treatment for breast cancer.
Doxorubicin and Cisplatin	Stearic acid, Precirol ATO, dimethyldioctadecylammonium bromide, triethylamine, soybean phosphatidylcholine, acetone, ethanol	In a breast cancer model, the in vivo study shows the highest anti-tumor activity. The produced NLCs may be utilized to co-deliver CDDP and DOX as part of a treatment for breast cancer.
Thymoquinone	Olive oil, lecithin, phospholipid, Polysorbate 80	TQ-NLC demonstrated a high drug loading capacity and encapsulation efficiency. TQ-NLC has the potential to be developed into a drug for treatment of breast cancer.
Resveratrol	stearic acid, oleic acid, folic acid, Poloxamer 188, Phospholipon 90 G	RSV-FANLCs provided encouraging prospects with regard to solubility, sustained release, and targeting potential.

Jyotiraditya Mall, Nazish Naseem, Md. Faheem Haider, Md Azizur Rahman, Sara Khan, Sana Naaz Siddiqui,

Nanostructured lipid carriers as a drug delivery system: A comprehensive review with therapeutic applications,
Intelligent Pharmacy, 2024, ISSN 2949-866X, https://doi.org/10.1016/j.ipha.2024.09.005.