Elsevier

Pharmacological Reports

Volume 71, Issue 1, February 2019, Pages 156-166
Pharmacological Reports

Review article
Nanostructured lipid carriers: A potential use for skin drug delivery systems

https://doi.org/10.1016/j.pharep.2018.10.008Get rights and content

Abstract

Skin application of pharmaceutical products is one of the methods used for drug administration. The problem of limited drug penetration via topical application makes searching for safe drug carriers that will provide an expected therapeutic effect of utmost importance. Research into safe drug carriers began with liposome structures, paving the way for work with nanocarriers, which currently play a large role as drug vehicles. Nanostructured lipid carriers (NLC) consist of blended solid and liquid lipids (oils) dispersed in an aqueous solution containing a surfactant. These carriers have many advantages: good biocompatibility, low cytotoxicity, high drug content; they enhance a drug’s stability and have many possibilities of application (oral, intravenous, pulmonary, ocular, dermal). The following article presents properties, methods of preparation and tests to assess the quality and toxicity of NLC. This analysis indicates the possibility of using NLC for dermal and transdermal drug application.

Introduction

The oral route is the most important and conventional method of drug administration. Unfortunately, oral drug delivery systems have many significant limitations, such as drug degradation in the gastrointestinal track (by enzymes, pH), pre-systemic metabolism or toxic side effects. One of the methods which could overcome problems associated with the oral route is transdermal drug delivery (TDD) [1,2]. Application of drugs in the liquid, semisolid or solid form to treat skin diseases has been used since the beginning of humanity. Later, the next goal was to use skin for transdermal drug delivery to provide the systemic therapy. The first transdermal therapeutic system was developed in 1981 in the form of a patch with scopolamine (Transdermal Scop®) for the treatment of motion sickness. Today, there is a great variety of transdermal products for drugs such as nitroglycerin, clonidine, fentanyl, nicotine, oestradiol, testosterone or diclofenac [3,4].

TDD has obvious advantages over other routes of delivery. It can improve compliance, especially for patients who do not tolerate oral dosage forms, including people who are unconscious or those with swallowing problems. It also allows for pain-free and safe administration of drugs, in addition to reducing the frequency of their application. Another advantage of TDD is assurance of more consistent serum drug levels, elimination of hepatic first-pass metabolism, avoidance of drug degradation in the gastrointestinal tract and reduction of side effects (e.g. gastrointestinal upsets) [1,5,6]. The main disadvantage of transdermal drug delivery concerns low permeability of skin, which limits drug penetration. Furthermore, some drugs and excipients used in transdermal formulations can cause skin irritation (erythema, itching, edema) or allergic reaction [7,8].

Section snippets

Problems with dermal and transdermal drug administration

Skin is the largest multilayered organ of the body, with a surface area of 1.7 - 2.0 m2. Microscopically, skin consists of three layers: the epidermis (outer layer), the dermis (middle layer) and subcutaneous tissue (inner layer). The epidermis is a stratified and squamous membrane composed of several cell layers and it can be divided into the non-viable epidermis (stratum corneum, SC) and the viable epidermis. The SC consists of keratin-filled corneocytes that are anchored in a lipophilic

Lipid-based formulations as effective dermal vehicles for drugs

Nanotechnology is a modern and rapidly evolving trend in dermal and transdermal drug delivery which includes several forms of nanocarriers such as liposomes, nanoemulsions, nanocrystals, polymeric nanoparticles, lipid nanocarriers and dendrimers. Lipid nanocarriers show essential advantages over conventional drug forms and they are formulated with biodegradable, non-toxic and non-irritant lipids. The small size (from 40 to 800 nm) of lipid nanocarriers allows to adhere them to the lipid film of

Conclusions

Applying drugs to the skin has become an evolutive method for treatment of local and systemic diseases. Replacing conventional dermatological drug forms (ointments, gels) with nanolipids has the main aim of obtaining small particle size and increased penetration of drugs through the skin. The modern form of lipid nanocarriers are nanostructured lipid carriers (NLC). NLC are used particularly for drugs that dissolve poorly in water. The process of obtaining an effective form of NLC requires

Financial support

This article was supported by Medical University of Bialystok grant (No. N/ST/ZB/18/001/2215).

Conflict of interest

The authors declare no conflicts of interest.

References (149)

  • C.C. Chen et al.

    Effects of lipophilic emulsifiers on the oral administration of lovastatin from nanostructured lipid carriers: physicochemical characterization and pharmacokinetics

    Eur J Pharm Biopharm

    (2010)
  • R.R. Patlolla et al.

    Formulation, characterization and pulmonary deposition of nebulized celecoxib encapsulated nanostructured lipid carriers

    J Control Release

    (2010)
  • C. Zhao et al.

    Preparation, macrophages targeting delivery and anti-inflammatory study of pentapeptide grafted nanostructured lipid carriers

    Int J Pharm

    (2013)
  • J. Pardeike et al.

    Development of an itraconazole-loaded nanostructured lipid carrier (NLC) formulation for pulmonary application

    Int J Pharm

    (2011)
  • A. Patil-Gadhe et al.

    Montelukast-loaded nanostructured lipid carriers. Part I: oral bioavailability improvement

    Eur J Pharm Biopharm

    (2014)
  • J. Shen et al.

    Mucoadhesive effect of thiolated PEG stearate and its modified NLC for ocular drug delivery

    J Control Release

    (2009)
  • J. Shen et al.

    Thiolated nanostructured lipid carriers as a potential ocular drug delivery system for cyclosporine A: improving in vivo ocular distribution

    Int J Pharm

    (2010)
  • B. Tian et al.

    Novel surface-modified nanostructured lipid carriers with partially deacetylated water-soluble chitosan for efficient ocular delivery

    J Pharm Sci

    (2012)
  • E. Gonzalez-Mira et al.

    Improved and safe transcorneal delivery of flurbiprofen by NLC and NLC-based hydrogels

    J Pharm Sci

    (2012)
  • X. Li et al.

    A controlled-release ocular delivery system for ibuprofen based on nanostructured lipid carriers

    Int J Pharm

    (2008)
  • N. Ustündağ-Okur et al.

    Preparation and in vitro-in vivo evaluation of ofloxacin loaded ophthalmic nano structured lipid carriers modified with chitosan oligosaccharide lactate for the treatment of bacterial keratitis

    Eur J Pharm Sci

    (2014)
  • P.O. Nnamani et al.

    Development of artemether-loaded nanostructured lipid carrier (NLC) formulation for topical application

    Int J Pharm

    (2014)
  • C. Puglia et al.

    Development, characterization, and in vitro and in vivo evaluation of benzocaine- and lidocaine-loaded nanostructrured lipid carriers

    J Pharm Sci

    (2011)
  • S.B. Lohan et al.

    Ultra-small lipid nanoparticles promote the penetration of coenzyme Q10 in skin cells and counteract oxidative stress

    Eur J Pharm Biopharm

    (2015)
  • M.F. Pinto et al.

    A new topical formulation for psoriasis: development of methotrexate-loaded nanostructured lipid carriers

    Int J Pharm

    (2014)
  • G. Chen-yu et al.

    Development of a quercetin-loaded nanostructured lipid carrier formulation for topical delivery

    Int J Pharm

    (2012)
  • E. Esposito et al.

    Progesterone lipid nanoparticles: scaling up and in vivo human study

    Eur J Pharm Biopharm

    (2017)
  • F. Eiras et al.

    Characterization and biocompatibility evaluation of cutaneous formulations containing lipid nanoparticles

    Int J Pharm

    (2017)
  • W.J. Lin et al.

    Nanostructured lipid carriers for transdermal delivery of acid labile lansoprazole

    Eur J Pharm Biopharm

    (2016)
  • C. Vitorino et al.

    Passive and active strategies for transdermal delivery using co-encapsulating nanostructured lipid carriers: in vitro vs. In vivo studies

    Eur J Pharm Biopharm

    (2014)
  • S.J. Park et al.

    Development of nanostructured lipid carriers for the encapsulation and controlled release of vitamin D3

    Food Chem

    (2017)
  • P. Severino et al.

    Optimizing SLN and NLC by 2(2) full factorial design: effect of homogenization technique

    Mater Sci Eng C

    (2012)
  • M.L. Kääriäinen et al.

    Nitrogen doping in atomic layer deposition grown titanium dioxide films by using ammonium hydroxide

    Thin Solid Films

    (2012)
  • A.Z. Alkilani et al.

    Transdermal drug delivery: innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum

    Pharmaceutics

    (2015)
  • J.L. Bolognia et al.

    Dermatology

    (2012)
  • Food and drug administration: approved drug products with therapeutic equivalence evaluations

    (2018)
  • M.R. Prausnitz et al.

    Transdermal drug delivery

    Nat Biotech

    (2008)
  • P.D. Gavin et al.

    Tocopheryl phosphate mixture (TPM) as a novel lipid-based transdermal drug delivery carrier: formulation and evaluation

    Drug Deliv Transl Res

    (2017)
  • H. Lee et al.

    Device-assisted transdermal drug delivery

    Adv Drug Deliv Rev

    (2017)
  • S. Sharma et al.

    A review on transdermal drug delivery

    IJAPBC

    (2012)
  • A.S. Kadam et al.

    Transdermal drug delivery: an overview

    Int J Res Dev Pharm L Sci

    (2014)
  • W. Montagna et al.

    The structure and function of skin

    (1974)
  • L. Bartosova et al.

    Transdermal drug delivery in vitro using diffusion cells

    Curr Med Chem

    (2012)
  • C.J. Mbah et al.

    Perspective on transdermal drug delivery

    J Chem Pharm Res

    (2011)
  • H. Tanwar et al.

    Transdermal drug delivery system: a review

    IJPSR

    (2016)
  • H. Todo et al.

    Permeation pathway of macromolecules and nanospheres through skin

    Biol Pharm Bull

    (2010)
  • C.M. Schoellhammer et al.

    Skin permeabilization for transdermal drug delivery: recent advances and future prospects

    Expert Opin Drug Deliv

    (2014)
  • A.D. Sezer

    Application of Nanotechnology in Drug Delivery

    (2014)
  • A. Ahad et al.

    Transdermal drug delivery: the inherent challenges and technological advancements

    Asian J Pharm Sci

    (2010)
  • K. Rehman et al.

    Recent advances in gel technologies for topical and transdermal drug delivery

    Drug Dev Ind Pharm

    (2013)
  • Cited by (83)

    • Transdermal formulations and strategies for the treatment of osteoporosis

      2022, Journal of Drug Delivery Science and Technology
    View all citing articles on Scopus
    View full text