Nanostructured lipid carriers (NLCs) as drug delivery platform: Advances in formulation and delivery strategies

NLCs have provoked the incessant impulsion for the development of safe and valuable drug delivery systems owing to their exceptional physicochemical and then biocompatible characteristics. Throughout the earlier period, a lot of studies recounting NLCs based formulations have been noticeably increased. They are binary system which contains both solid and liquid lipids aiming to produce less ordered lipidic core.

Their constituents particularly influence the physicochemical properties and effectiveness of the final product. NLCs can be fabricated by different techniques which are classified according to consumed energy. More utilization NLCs is essential due to overcome barriers surrounded by the technological procedure of lipid-based nanocarriers’ formulation and increased information of the core mechanisms of their transport via various routes of administration. They can be used in different applications and by different routes such as oral, cutaneous, ocular and pulmonary.

This review article seeks to present an overview on the existing situation of the art of NLCs for future clinics through exposition of their applications which shall foster their lucid use. The reported records evidently demonstrate the promise of NLCs for innovate therapeutic applications in the future.

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Introduction

Nanoparticulate systems present potential platform for drug therapy that can improve its performance and rise above its limitations. Among the different investigated nano-systems, lipid nanoparticles keep immense promise in the area of drug delivery. Historically, Müller and Gasco around 1990s were firstly developed and nominated solid lipid nanoparticles (SLN) for the sake of avoiding organic solvents involved in preparation of polymeric nanoparticles (H. Muller, Shegokar, and M. Keck 2011). SLN became one of the most emerging systems as it provided better stability than liposomes (previously developed), solidified at body temperature which controlled drug release and deprived from toxic effects associated with organic solvent involvement (Teeranachaideekul, Müller, and Junyaprasert 2007). As its lipid content represented only by solid lipid, low drug payload is the major challenge for applicability owing to internal rearrangement of crystal lattice and then drug expulsion. In order to increase drug loading, the second generation lipid nanoparticles; nanostructured lipid carriers (NLCs) was developed. NLCs are binary system which contains both solid and liquid lipids which in turn produced less ordered lipidic core (Muller, Radtke, and Wissing 2004)^,(Radtke, Souto, and Müller 2005). This imperfection of internal arrangement aids more drug accommodation. So, NLCs overweigh SLN (Figure 1) as the former can encapsulate higher drug amounts, contains lower water content and improves drug entrapment with minimized leakage during storage (Mehnert and Mäder 2012). They also since then, researchers paid attention to NLCs and discovered different applications.

In this review paper, we have tried to present an inclusive elucidation of the following features: a) a concise overview of NLCs’ components and their integration to technological aspects of the formulations; b) the current art in development of NLCs together with their different categories; c) major applications and current challenges for the development of NLCs as delivery systems by different routes of administration.

Table 1. Commonly used liquid lipids and solid lipids for preparation of NLCs:

Component	Name	Purpose and reference(s)
Liquid lipids	Oleic Acids	Enhancement of oral bioavailability of simvastatin (Tiwari and Pathak 2011) and carbamazepine (Mohammed Elmowafy et al. 2018).
		Topical delivery of spironolactone for treatment of acne vulgaris (Kelidari et al. 2016).
	Caprylic/Capric triglycerides (Miglyol 812)®	Enhancement of oral bioavailability of thymoquinone (M. Elmowafy et al. 2016) and vinpocetine (Zhuang et al. 2010).
	α-tocopherol/ Vitamin E	Improvement of Quercetin anti-breast cancer activities in vitro (Sun et al. 2014).
	Soy bean oil	Pulmonary delivery of itraconazole (Pardeike et al. 2011).
	Black cumin oil	Produces synergistic effect with marigold/carrot extract in inhibition of reactive free radicals(Lacatusu et al. 2020).
	Caraway  essential oil	Accelerates wound healing of the infected excision wounds(Tazehjani, Farahpour, and Hamishehkar 2021).
	Olive oil	Produces oleuropein loaded NLCs with suitable physico-chemical stability and reduces the possible cytotoxicity effect of residual surfactants(Huguet-Casquero et al. 2020).
	Sweet almond oil	Improves the protection and stability of Cinnamon essential oil loaded NLCs(Bashiri et al. 2020).
	Squalene	Topical delivery of calcipotriol and Methotrexate combination (Y.-K. Lin et al. 2010) and psoralen (Fang et al. 2008).
		Enhancement of oral bioavailability of Lovastatin (C.-C. Chen et al. 2010).
	Capmul MCM C8	Improvement of Tacrolimus bioavailability and lymphatic distribution (S. Khan et al. 2016).
		Sustained release of Raloxifene hydrochloride with improvement in bioavailability (Shah et al. 2016).
Solid lipids	Compritol 888 ATO	Skin permeating of fluocinolone acetonide for treatment of psoriasis (Pradhan et al. 2015) and clobetasol propionate in topical gel (Nagaich and Gulati 2016).
		Enhancement of oral bioavailability of fenofibrate (Tran et al. 2014).
	Precirol ATO 5	Skin delivery of dapsone (Mohammed Elmowafy et al. 2019).
		Improvement of wound healing efficacy of rhEGF in a porcine full-thickness excisional wound model (Gainza et al. 2015).
	Stearic Acid	Topical delivery of tretenoin (Ghate et al. 2016).
		Controlled release and acid protection of progesterone (M. Elmowafy et al. 2018).
	Glyceryl Monostearate	Enhancement of oral bioavailability Omega-3 fatty acids (Muchow et al. 2009) and raloxifene (Shah et al. 2016).
	Cetyl palmitate	Topical delivery of coenzyme Q10 (Teeranachaideekul et al. 2007).
	Gelucire®	Improving miconazole local delivery to the oral mucosa and antifungal activity (A. I. Mendes et al. 2013).
		Improving in vivo ocular bioavailability of mangiferin (Liu et al. 2012).

Article information: Mohammed Elmowafy, Mohammad M. Al-Sanea, Nanostructured lipid carriers (NLCs) as drug delivery platform: Advances in formulation and delivery strategies, Saudi Pharmaceutical Journal, 2021. https://doi.org/10.1016/j.jsps.2021.07.015.