Editorial For reprint orders, please contact: [email protected]

Solid lipid nanoparticle-incorporated gel: the future treatment for skin infections? “Why is there such an increased interest in solid lipid nanoparticles? What makes

the solid lipid nanoparticulate system promising for the treatment of skin infections? The answer lies in the advantages that solid lipid nanoparticles possess over other lipidic or nonlipidic drug delivery systems.” KEYWORDS: gel n skin targeting n solid lipid nanoparticle n topical application

Abhinesh Kumar Solid lipid nanoparticles (SLNs) are promising lipid-based nanoparticulate carriers owing to their versatility, regulatory acceptance, scalability, commercialization potential and ability to incorporate all types of drugs for all routes of administration. SLNs are gaining popularity as drug carriers and cosmetics for topical application owing to their ability to prolong contact time, skin adhesion and skin targeting. At this rate, it would not be out of context to envisage that SLN-based formulations will be the backbone of treatment for skin infections in the near future. SLNs are novel drug carrier systems consisting of a solid matrix composed of a lipid that is solid at both room and body temperatures [1]. Why is there such an increased interest in SLNs? What makes the solid lipid nanoparticulate system promising for the treatment of skin infections? The answer lies in the advantages that SLNs possess over other lipidic or nonlipidic drug delivery systems. SLNs hold the combined advantages of emulsions, liposomes and solid particles [2]. These advantages include: improved drug stability, enhanced bioavailability, high inclusion rate for lipophilic substances, the ability to incorporate drugs with different physicochemical properties, small particle size allowing close contact with biological membranes, and targeting potential. SLNs also minimize drug leakage, degradation and provide flexibility in modulating its release. Skin-specific advantages include local acceptability, increased surface area, increased adhesive properties, formation of occlusive film leading to increased skin hydration, increased skin penetration and close interaction with the skin lipids. Since SLNs are composed of skincompatible lipids, they are devoid of skin irritation or sensitization issues [3]. Another advantage

of this system is regulatory compliance. SLNs can be prepared using the majority of excipients such as a wide range of lipids, polymers and surfactants that are currently being used in topical/dermal products. SLNs can be prepared by various methods, such as high pressure homogenization (hot or cold), solvent emulsification–evaporation, emulsification–diffusion and phase inversion, out of which high pressure homogenization is easily scalable from laboratory to industry and can be further incorporated in gel [4]. Drug release from SLNs is often found to be biphasic with an initial burst release and subsequent sustained release. Burst release is higher when SLNs are produced by a hot homogenization technique and can be minimized by using low surfactant concentration. For a topical gel containing SLNs, all excipients used in marketed topical cosmetics and dermal pharmaceutical products can be used. The SLN dispersion can be incorporated into commonly used dermal formulations, such as hydrogels or creams, to get a topical dosage with the desired semisolid consistency [5,6]. After topical application of a SLN-based gel, a lipidic film forms over the skin, which has an occlusive effect with affinity for the stratum corneum, which increases drug penetration or water content in the upper epidermis layers. This makes sustained release from these carriers possible, which is an important tool when it is necessary to supply the drug over an extended period of time [7,8]. Occlusion favors the drug penetration into the skin while an increase in water content of the skin decreases the symptoms of atopic eczema and improves the appearance as healthy human skin [9,10]. Due to the high affinity of SLNs to the stratum corneum, the bioavailability of the entrapped material in the skin is augmented.

10.2217/NNM.13.171 © 2013 Future Medicine Ltd

Nanomedicine (2013) 8(12), 1901–1903

Drug Delivery Research Laboratory, TIFAC Center of Relevance & Excellence in NDDS, Shri G H Patel Pharmacy Building, Pharmacy Department, The Maharaja Sayajirao University of Baroda, Fatehgunj, Vadodara 390002, Gujarat, India

Krutika K Sawant

Author for correspondence: Drug Delivery Research Laboratory, TIFAC Center of Relevance & Excellence in NDDS, Shri G H Patel Pharmacy Building, Pharmacy Department, The Maharaja Sayajirao University of Baroda, Fatehgunj, Vadodara 390002, Gujarat, India Tel.: +91 265 2794051 Fax: +91 265 2423898/2418927 [email protected]

part of

ISSN 1743-5889

1901

Editorial

Kumar & Sawant

SLNs enhance the penetration and transport of active substances, particularly lipophilic agents, intensifying their skin concentration [2,11,12]. This should be confirmed by ex vivo drug penetration studies with the intention to assess the risk of using SLNs in topical products. In the treatment of skin infections, the goal is to maximize drug retention in skin while minimizing its absorption in the systemic circulation. It is important that SLN-incorporated gel should target the active molecule to the skin, sufficiently penetrating into the skin layers but not too deep so as to result in systemic absorption of the active ingredient. Factors affecting the degree of penetration include the interaction of lipids/surfactants (present in SLNs) with skin lipids, film formation properties and resulting hydration of skin. Maia et al. reported optimization of SLN compositions in order to obtain drug enrichment in the upper layers of skin, thus minimizing its systemic availability [13].

“…the promising in vitro and ex vivo findings by a large number of researchers need to be substantiated by clinical studies before this treatment modality can be made commercially available.”

SLNs have proven to be most proficient in promoting penetration into the stratum corneum. However, a topically applied SLN dispersion is not able to remain on the skin for a long period owing to its low viscosity. Moreover, SLNs are significantly less stable in dispersion form and have been shown to undergo aggregation, polymorphic transitions and drug leakage. Hence, it is necessary to incorporate the SLNs in a semisolid vehicle. Of the various bases used, gels are preferred due to their elegance, transparency, ability to take up large quantities of water and nongreasy nature. When SLNs are incorporated into gel, the residence time increases, particle aggregation reduces and, furthermore, the gel network hampers the polymorphic transitions of the lipids, thus enhancing the stability of SLNs [14]. Recently, we developed terbinafine hydrochloride-loaded SLNs and the SLN-incorporated carbopol gel reduced the fungal burden in rats in a shorter duration of time compared with the marketed formulation (Daskil®; Novartis Pharma) [15]. The SLNincorporated carbopol gel was found to be more effective because of improved contact, adhesion, occlusion and sustained release. Furthermore, our clinical study demonstrated the promising role of acitrecin-loaded nanostructured lipid 1902

Nanomedicine (2013) 8(12)

carriers (NLCs) incorporated into carbopol gel for psoriasis treatment [16]. The therapeutic response was improved and adverse effects of therapy were reduced compared with the conventional treatment. Thus, by targeting the drug to the skin, SLNs can reduce the systemic access of drugs and, thus, reduce systemic side effects.

Difficulties & challenges Although SLNs have demonstrated several beneficial properties, they still need to overcome a number of limitations. These include limited loading of hydrophilic drugs, changes in drug release profile upon storage and lipid polymorphisms leading to drug leakage during storage. Hence, NLCs produced using blends of solid and liquid lipids have been developed as a second generation of SLNs and are attracting attention as alternatives to SLNs. However, despite many claims, the superiority of NLCs over SLNs is yet to be verified because of contradictory results by some researchers [17–19]. In a nutshell, the major challenge is to ensure that these nanocarriers clear the hurdles of safety, efficacy, regulatory approval and patient compliance before their clinical use. Conclusion & future perspective SLN-incorporated gel is an attractive carrier system for the treatment of skin infections. It is rapidly developing into a next-generation drug delivery system as an alternative to existing oral therapy and conventional semisolid formulations for the treatment of skin infections. How these SLNs modify and interact with the skin lipids leading to drug penetration needs to be better understood. Potential systemic effects after dermal application of SLN-incorporated gel should be considered in order to formulate it as a safe dermal product for skin targeting. Visualization of SLNs is important after application of the gel to evaluate their interaction with cutaneous skin structures. Additional efforts are vital to ensure dermal localization of the drug/formulation for a better pharmaceutical effect. In recent years, lipid nanoparticulate-based topical formulations have appeared in the market (Cutanova Nanorepair Q10 and Nanobase as an anti­aging cream and moisturizer, respectively) for cosmetic use. This may be considered as a positive step towards the introduction of similar products into the pharmaceutical market, provided quality standards can be incorporated in their large-scale production. Finally, the promising in vitro and ex vivo findings by a large number of researchers need to be substantiated by clinical future science group

Solid lipid nanoparticle-incorporated gel: the future treatment for skin infections?

studies before this treatment modality can be made commercially available. SLN-incorporated gel for treatment of skin infection enables researchers to study a potential delivery system for skin targeting of drugs. SLN-incorporated gel holds the advantages of liposomes, emulsions, solid particles and gel. Such an innovative reformulation of a drug could extend its patent life and could lead to reduced side effects, achieving a more effective therapy. However, current findings are not enough to make it a successful formulation on the market. Further preclinical and clinical

References 1

2

3

4

5

6

Müller RH, Mehnert W, Lucks JS et al. Solid lipid nanoparticles (SLN) – an alternative colloidal carrier system for controlled drug delivery. Eur. J. Pharm. Biopharm. 41(1), 62–69 (1995). Müller RH, Radtke M, Wissing SA. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv. Drug Deliv. Rev. 54(Suppl. 1), S131–S155 (2002). Pople PV, Singh KK. Development and evaluation of topical formulation containing solid lipid nanoparticles of vitamin A. AAPS PharmSciTech 7(4), E63–E69 (2006). Shegokar R, Singh KK, Müller RH. Production and stability of stavudine solid lipid nanoparticles – from lab to industrial scale. Int. J. Pharm. 416(2), 461–470 (2011). Bhalekar MR, Pokharkar V, Madgulkar A, Patil N. Preparation and evaluation of miconazole nitrate-loaded solid lipid nanoparticles for topical delivery. AAPS PharmSciTech 10(1), 289–296 (2009). Montenegro L, Sinico C, Castangia I, Carbone C, Puglisi G. Idebenone-loaded solid lipid nanoparticles for drug delivery to the skin: in vitro evaluation. Int. J. Pharm. 434 (1–2), 169–174 (2012).

future science group

7

Editorial

studies are needed to validate the therapeutic potential of this drug delivery system. Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

Müller RH, Mäder K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery – a review of the state of the art. Eur. J. Pharm. Biopharm. 50(1), 161–177 (2000).

8

Wissing S, Müller R. Solid lipid nanoparticles (SLN) – a novel carrier for UV blockers. Pharmazie 56(10), 783–786 (2001).

9

de Vringer T, de Ronde HA. Preparation and structure of a water-in-oil cream containing lipid nanoparticles. J. Pharm. Sci. 84(4), 466–472 (1995).

10 Mei Z, Chen H, Weng T, Yang Y, Yang X.

Solid lipid nanoparticle and microemulsion for topical delivery of triptolide. Eur. J. Pharm. Biopharm. 56(2), 189–196 (2003). 11 Padois K, Cantieni C, Bertholle V, Bardel C,

Pirot F, Falson F. Solid lipid nanoparticles suspension versus commercial solutions for dermal delivery of minoxidil. Int. J. Pharm. 416(1), 300–304 (2011). 12 Wissing SA, Müller RH. The influence of

solid lipid nanoparticles on skin hydration and viscoelasticity – in vivo study. Eur. J. Pharm. Biopharm. 56(1), 67–72 (2003). 13 Maia CS, Mehnert W, Schäfer-Korting M.

Solid lipid nanoparticles as drug carriers for topical glucocorticoids. Int. J. Pharm. 196(2), 165–167 (2000). 14 Jenning V, Schäfer-Korting M, Gohla S.

Vitamin A-loaded solid lipid nanoparticles

www.futuremedicine.com

for topical use: drug release properties. J. Control Release 66(2–3), 115–126 (2000). 15 Vaghasiya H, Kumar A, Sawant K.

Development of solid lipid nanoparticles based controlled release system for topical delivery of terbinafine hydrochloride. Eur. J. Pharm. Sci. 49(2), 311–322 (2013). 16 Agrawal Y, Petkar K, Sawant K.

Development, evaluation and clinical studies of Acitretin loaded nanostructured lipid carriers for topical treatment of psoriasis. Int. J. Pharm. 401(1–2), 93–102 (2010). 17 Kovacevic A, Savic S, Vuleta G, Müller RH,

Keck CM. Polyhydroxy surfactants for the formulation of lipid nanoparticles (SLN and NLC): effects on size, physical stability and particle matrix structure. Int. J. Pharm. 406(1–2), 163–172 (2011). 18 Souza LG, Silva EJ, Martins AL et al.

Development of topotecan loaded lipid nanoparticles for chemical stabilization and prolonged release. Eur. J. Pharm. Biopharm. 79(1), 189–196 (2011). 19 Tiwari R, Pathak K. Nanostructured lipid

carrier versus solid lipid nanoparticles of simvastatin: comparative analysis of characteristics, pharmacokinetics and tissue uptake. Int. J. Pharm. 415(1–2), 232–243 (2011).

1903

Solid lipid nanoparticle-incorporated gel: the future treatment for skin infections?

Solid lipid nanoparticle-incorporated gel: the future treatment for skin infections? - PDF Download Free
720KB Sizes 0 Downloads 0 Views