Abstract

One cutting-edge method of medication administration is nanostructured lipid carriers, or NLCs. Enhanced bioavailability, controlled release, and targeted administration are just a few of the ways these newer drug delivery systems aim to improve upon older ones. Nanostructured lipid carriers (NLCs) exhibit more flexibility and possess a less ordered molecular arrangement in comparison to Solid Lipid Nanoparticles (SLNs). This is attributed to their composition, which comprises a blend of solid and liquid lipids.
As components of formulations, lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are appealing because they are easy to fabricate, biocompatible, biodegradable, and scalable. The review covers the manufacturing techniques, limits, toxicity, optimisation of formulation, production methods, freeze drying, and drug release for new SLNs and lipid nanocarriers. It also discusses the newer SLNs’ simplicity and scalability. This review delves into the ideas, advantages, and uses of NLCs in the treatment of several illnesses.

Keywords: SLN; NLC; Applications; Mechanism; Advantages; Challenges and Future Perspectives

Introduction

In recent years, researchers have focused on several drug delivery methods, with the development of nanomedicine and nano delivery systems being an intriguing aspect of this [1]. Due to biotoxicity, the field of lipid-based DNA/RNA nanocarriers has been actively developing [2]. Lipid nanoparticles are often made from biodegradable and biocompatible lipids, which means they have minimal toxicity and no adverse effects. When broken down in living organisms, some polymeric nanoparticles cause harm [3]. Improved drug bioavailability, biocompatibility, and physical variety of lipids make them a suitable drug delivery vehicle. Furthermore, there are numerous ways in which lipid preparations can enhance drug absorption. These strategies involve enhancing the drug’s solubility, diluting it in the intestines, blocking Pgp efflux transporters, decreasing the activity of cytochrome P450 enzymes (CYPs), and enhancing membrane permeability affects the speed of lymphatic transportation. There are two primary types of lipid nanoparticles: Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs). NLCs were developed as a solution to address the limitations of SLNs and are therefore considered the next iteration of these nanoscale lipid carriers, with SLNs being the first version. The number 6. My darling, good morning. Like liposomes and nanoemulsions, SLNs are composed of biocompatible adjuvants that are acceptable to the body. Furthermore, matrix materials can produce an enhanced release profile by obtaining transport material by enzymatic degradation and providing maximal flexibility. Emulsion with SLN (HPH) [4,5].

Recent progress in SLNs

Lipid-containing nanospheres exhibiting Photon Correlation Spectra (PCS) ranging from 50 to 1000 nm are referred to as SLNs. The lipid components may consist of a combination of waxes, glycerides, or pure triglycerides; these are substances that are formed when the human body heats up and are then mixed with an appropriate surfactant. Other drug delivery methods include polymer microparticles and nanoparticles, liposomes, or emulsions. SLNs are top-notch lipid products due to several factors: Firstly, the product is composed of biodegradable, non-toxic, and biocompatible components. Secondly, the drug’s encapsulation results in an average particle size ranging from 50 to 1000 nm. Lastly, the procedure is both rapid and inexpensive [6]. New evidence shows that people can take many agents,including anti-cancer medication, and do diagnostic and therapy simultaneously. Researchers Kuangote et al. [7] demonstrated that c(RGDyK)-carrying SLNs are effective vectors for delivering IR780 to carbon dots and cancer cells [6,8,9, 7,10]. The use of quantum dots into contrast-based SLNs has opened up new possibilities for cancer therapy [11]. SLNs can be utilised for the transport of biomacromolecules and tiny medicines, such as peptides and proteins, for specialised applications. The specific drawbacks of SLNs are low loading capacity, polymorphic change leakage, and high dispersion water content [12]. The crystal network, the physical and chemical structural components of solid lipid matrices, the polymorphic state of lipids, and the solubility of medicines in dissolved lipids. Researchers Müller et al. [13] To enhance medication distribution to the location of infection (tissue), antibiotics can be included into SLNs. Two- and three-dimensional cell cultures of the U87MG cell line, as well as sixteen two-dimensional cell models of the human alveolar adenocarcinoma cell line (A549) (SLN preparation), were used to assess the antiviral characteristics of the SLN combinations. Scaling up manufacturing and future nano system standardisation in the biomedical area are both made possible by the usage of microfluidics in this context.

Recent Progress in NLCs [14]

The NLC system was implemented to rectify the issues with SLN.NLC is primarily composed of a matrix that includes both solid and liquid lipids, but it can also include other types of lipid molecules. These, in contrast to SLNs, allow additional drug molecules to enter the matrix by creating structural flaws. At normal temperature, the NLC matrix is solid, even though its lipid composition is liquid. Maintaining a constant NLC is as simple as changing the liquid-to-solid lipid ratio. When it comes to preventing particle agglomeration from the solid matrix, NLC is far superior to emulsions. SLN’s benefits, including biodegradability, chemical resistance to hostile conditions, protection from organic solvents during manufacture, and drug release ibility are also present in NLC. It also has a low toxicity potential. The significance of NLCs in therapy has been highlighted by recent studies. Photodynamic therapy for breast cancer has been associated with the use of multifunctional nanocarriers of CXCR4-targeting NLC encapsulated with IR 780 and coumarin 6 fluorescent dyes. Things that can be photographed [15]. Created NLC [14] with quantum dots and paclitaxel that inhibits tumour cell growth in a mouse model of hepatocellular carcinoma.

Approaches of Preparation [16]

The controlled synthesis of nanoparticles has been investigated using several physical approaches. Among the many benefits offered by these approaches are their low energy consumption, low toxicity, and high efficacy21. Supercritical fluid methods, ultrafiltration, surfactant flocculation, and HPH are all examples of such approaches (Kanwar et al. [17]; Passos et al.; Malik et al. [16]; Lie et al. 2021; Vinchhi et al. 2021).

Lyophilization of Lipid Nanoparticles [17]

One way to make SLNs more physically and chemically stable is to lyophilize them. The colloidal nanoparticle suspension will be weakened by the forces induced throughout the freeze-drying process. The stability of the nanoparticle colloidal system can be compromised if the particles fuse or aggregate irreversibly. To be honest, adding two additional models for conversion will just make things more complicated. As the water evaporates and the sample freezes, the vacuum goes through a significant transformation, going from water dispersion to powder. The impact of freezing, which can alter pH and osmotic pressure, can lead to stability issues with frozen samples. Lipid nanoparticles with their many potential uses and delivery mechanisms Topical, intravenous, ocular, oral, and cerebral delivery are some of the methods of administration that have been discussed in numerous studies when discussing lipid nanoparticle production.

The Topical Route of Administration [18]

Skin-Worldwide, there is controversy surrounding diseases that are related to skin penetration. The main challenge in treating these diseases is the inability of medicine to effectively penetrate the skin due to the presence of the stratum corneum, which acts as a barrier. However, it is possible to overcome this barrier by changing the permeability of the skin from the follicular or transcellular state to the paracellular state. SLN (solid lipid nanoparticles) and NLC (nanostructured lipid carriers) have been developed to enhance skin penetration. It has been observed that lyophilized SLN preparations without cryoprotectants can lead to an increase in the size of SLN particles.

Oral Administration [19]

“Low oral bioavailability due to the significant hepatic firstpass effect and/or partial drug solubility is the primary obstacle in oral medication administration. Drug delivery systems based on nanoparticles are one approach to increasing oral bioavailability. The oral absorption of medications can be improved by incorporating chitosan into nanoparticles (Enayatifard et al. [19]; Tan and Billa, 2021). The extra dose forms of NLC and SLN aid in keeping the plasma levels steady. Additional critical concerns with oral medication administration include the P-glycoprotein efflux pump and enzymatic or chemical degradation. Nanoparticles of lipids improve lymphatic transport and block the first-pass effect in the liver. For instance, baicalin NLC carrier technology may improve bioavailability when taken orally.

Ocular administration [20]

The intricate structure and function of the eye make ocular medication administration difficult. It is common practice to inject medicine into the eye’s frontal lobe. Obstacles such lacrimal tears, corneal epithelium, ocular blood barrier, and conjunctival blood flow can be tough to overcome. Lipid nanoparticles, on the other hand, provide a workaround by regulating medication release, protecting it from enzymes produced by the lacrimal gland, and allowing it to pass through the blood vessels of the eye.

Parenteral Administration [21]

“Lipid nanoparticles can be administered via intramuscular, subcutaneous, intravenous, or targeted injection. While NLC is a suitable alternative, SLN is not an appropriate carrier due to limited drug availability. The NLC formulation with the smallest particle size (98 nm), highest encapsulation efficiency, and narrowest particle size distribution was achieved using surfactants and wax (HLB × 9) as lipids, along with a 5% lipid concentration (Galv et al. [20]).

Pulmonary Delivery [22]

“A non-invasive way to distribute medications locally or to particular areas is through pulmonary delivery systems. Medicines are less expensive and have fewer adverse effects when this strategy is used. Researchers have looked at the potential of lipid nanoparticles containing SLN and NLC to treat pulmonary disorders. When it comes to treating pulmonary artery disease, for example, phosphodiesterase type 5 inhibitors like sildenafil citrate play a crucial role. With an encapsulation effectiveness ranging from 88% to 100%, these nanoparticles have demonstrated a drug release profile that lasts for 24 hours. The drug encapsulation and colloidal stability of SLNs are affected by sterilisation by autoclaving and atomization with a jet nebulizer, suggesting that they have promise as pulmonary delivery methods.

Brain Delivery

Because of the blood-brain barrier, it is very difficult to get medications to the brain. Because they may pass through the reticuloendothelial system (RES), nanoparticles are strong candidates for medication delivery to the brain. Problems with drug reabsorption into circulation and insufficient pharmacological penetration of the blood-brain barrier are two major obstacles to brain medication delivery. Colloidal drug delivery materials including SLNs and NLCs have been used to solve these problems. A new levofloxacin/doxycycline (LEVO/DOX) formulation was developed by filling a solid lipid nanoparticle (SLN) with the medications using a process of high-speed homogenization and ultrasonic emulsification. Pharmacokinetic tests demonstrated that the SLNHPMC gel considerably enhanced brain peak pressure and AUC0360 min compared to intranasal medication without LEVO/DOX, indicating its efficacy in the blood and brain. Nanomedicines have been authorised for medical use. Several nanotechnologies and nanomaterials have been granted regulatory approval, and a subset of them are now undergoing additional examination in clinical trials. The mentioned antibiotics include doxorubicin, cimepilimab, paclitaxel, amphotericin B, ambisome, and natamycin [23,24].

Mechanism of Action [13]

The NLCs enhance drug delivery through various mechanisms:
• Enhanced Bioavailability: Increased solubility of drugs that are poorly soluble in water.
• Controlled Release: Sustained and controlled drug release profiles.
• Targeted Delivery: Ability to modify surface properties for targeted delivery to specific tissues or cells.

Advantages of NLCs [25,26]

• Enhanced Stability: Reduced drug degradation and enhanced shelf life.
• High Drug Loading: Increased capacity for drug incorporation due to the imperfect matrix structure.
• Biocompatibility and Safety: Use of biocompatible and biodegradable lipids reduces toxicity.
Challenges and Future Perspectives [27] • Scale-Up and Manufacturing: Challenges in large-scale production and reproducibility.
• Regulatory Approval: Need for comprehensive clinical trials and regulatory approvals.
• Targeted Delivery: Further research is required to enhance targeted delivery and reduce off-target effects.

Conclusion

“There are a number of advantages to using lipid nanoparticles as a drug delivery vehicle rather than the more conventional colloidal and polymeric nanocarriers. Advantages of lipid carriers include their biodegradability, biocompatibility, simplicity of expansion, and the capacity to give controlled release. Lipid nanoparticles, which may be administered by a variety of methods, fall into two main types: solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). Using various surfactant and lipid combinations at varied doses, many papers evaluate the cytotoxicity of SLN/NLC. The majority of tests indicated minimal levels of cytotoxicity. Take into account the issues related to the inherent fragility of nanoparticles, which frequently result in the formation of unwanted gels or aggregates when utilised in drug administration, posing potential hazards. The reported adverse effects may be caused by the choice of excipient in certain instances. Hence, the crucial criteria for ensuring the safety of SLN and NLC are the careful selection of the optimal quantity of SLN/ NLC and additives. The use of surface modification is also beneficial in mitigating these issues. The PEG nanoparticle layer serves as a protective barrier, preventing the surface from aggregating and being cleared by the reticuloendothelial system (RES), therefore prolonging its activity in the bloodstream. Furthermore, it has been documented that formulations using surfactants to stabilise the product exhibit lower toxicity compared to lipid nanoparticles used alone. The safety of poloxamer 188 and polysorbate 80, which are frequently employed as surfactants in SLN and NLC formulations, has been well proven. SLN and NLC have the drawback of being capable of inducing oxidative stress, which in turn leads to an inflammatory response. Nevertheless, the available data is restricted in scope. SLNs and NLCs are promising options that have the potential to enable the simultaneous delivery of both hydrophilic and hydrophobic medicines. The effective and controlled entry of medications into the body is a crucial aspect of SLN/NLC drug delivery. This approach helps minimise adverse effects and enables treatment that targets the underlying cause of the disease rather than just alleviating its symptoms. Hence, lipid nanoparticles, specifically tiny particles, play a crucial role in the administration of many pharmacological products to proteins and genes.”