Solid lipid nanoparticles (SLN) of tretinoin: potential in topical delivery

The objective of this investigation was to develop solid lipid nanoparticles (SLN) of tretinoin (TRE) with the help of facile and simple emulsification-solvent diffusion (ESD) technique and to evaluate the viability of an SLN based gel in improving topical delivery of TRE. The feasibility of fabricating SLN of TRE by the ESD method was successfully demonstrated in this investigation. The developed SLN were characterized for particle size, polydispersity index, entrapment efficiency of TRE and morphology. Studies were carried out to evaluate the ability of SLN in improving the photostability of TRE as compared to TRE in methanol. Encapsulation of TRE in SLN resulted in a significant improvement in its photostability in comparison to methanolic TRE solution and also prevented its isomerization. Furthermore, the skin irritation studies carried out on rabbits showed that SLN based TRE gel is significantly less irritating to skin as compared to marketed TRE cream and clearly indicated its potential in improving the skin tolerability of TRE. In vitro permeation studies through rat skin indicated that an SLN based TRE gel has permeation profile comparable to that of the marketed TRE cream.     

Solid lipid nanoparticles (SLN) as ocular delivery system for tobramycin

Aim of this study was to evaluate solid lipid nanoparticles (SLN) as carriers for topical ocular delivery of tobramycin (TOB). The SLN were in the colloidal size range (average diameter below 100 nm; polydispersity index below 0.2) and contained 2.5% TOB as ion-pair complex with hexadecyl phosphate. The preocular retention of SLN in rabbit eyes was tested using drug-free, fluorescent SLN (F-SLN): these were retained for longer times on the corneal surface and in the conjunctival sac when compared with an aqueous fluorescent solution. A suspension of TOB-loaded SLN (TOB-SLN) containing 0.3% w/v TOB was administered topically to rabbits, and the aqueous humour concentration of TOB was determined up to six hours. When compared with an equal dose of TOB administered by standard commercial eyedrops, TOB-SLN produced a significantly higher TOB bioavailability in the aqueous humour.     

固脂纳米粒(SLN)药物释放系统的研究进展

目的综述固脂纳米粒作为药物释放系统的最新研究进展。方法依据近年来国内外文献资料 ,将固脂纳米粒的制备方法、药物载入、药物释放、特性分析及其在药学领域的应用情况进行了概括。结果固脂纳米粒的主要制备方法为乳化法和微乳法 ;通过调整制备工艺参数可调整药物的包封率和释药曲线 ;固脂纳米粒可供多途径给药。结论固脂纳米粒在药学领域有广阔的发展前景     

Solid lipid nanoparticles as drug carriers for topical glucocorticoids

Recent investigations both in vitro and in human subjects proved the benefit/risk ratio of prednicarbate (PC) to exceed those of halogenated topical glucocorticoids about 2-fold. To obtain a further highly desired increase by drug targeting to viable epidermis, PC was incorporated into solid lipid nanoparticles (SLN). Keratinocyte and fibroblast monolayer cultures, reconstructed epidermis and excised human skin served to evaluate SLN toxicity and PC absorption. Well-tolerated preparations (e.g. cellular viability 94.5% following 18 h incubation of reconstructed epidermis) were obtained. PC penetration into human skin increased by 30% as compared to PC cream, permeation of reconstructed epidermis increased even 3-fold. The present study shows the great potential of SLN to improve drug absorption by the skin.     

Solid lipid nanoparticles (SLN) for topical drug delivery: incorporation of the lipophilic drugs N,N-diethyl-m-toluamide and vitamin K

Solid lipid nanoparticles (SLN) for topical delivery were prepared by high pressure homogenization using solid lipids. The lipophilic agents DEET (N,N-diethyl-m-toluamide) and vitamin K were used as model drugs. These topical agents were incorporated into SLN which were characterized. Differential scanning calorimetry studies were performed in order to detect probable interactions in the SLN dispersions. Physical stability of SLN in aqueous dispersions and the effect of drug incorporation into SLN were investigated by photon correlation spectroscopy and zeta potential measurements. Characterization and short-term stability studies showedthat DEET and vitamin K are good candidates for topical SLN formulations.     

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for application of ascorbyl palmitate

The aim of this study was to improve the chemical stability of ascorbyl palmitate (AP) in a colloidal lipid carrier for its topical use. For this purpose, AP-loaded solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and for comparison, a nanoemulsion (NE) were prepared employing the high pressure homogenization technique and stored at room temperature (RT), 4 degrees C and 40 degrees C. During 3 months, physical stability of these formulations compared to placebo formulations which were prepared by the same production method, was studied including recrystallization behaviour of the lipid with differential scanning calorimetry (DSC), particle size distribution and storage stability with photon correlation spectroscopy (PCS) and laser diffractometry (LD). After evaluating data indicating excellent physical stability, AP-loaded SLN, NLC and NE were incorporated into a hydrogel by the same production method as the next step. Degradation of AP by HPLC and physical stability in the same manner were investigated at the same storage temperatures during 3 months. As a result, AP was found most stable in both the NLC and SLN stored at 4 degrees C (p > 0.05) indicating the importance of storage temperature. Nondegraded AP content in NLC, SLN and NE was found to be 71.1% +/- 1.4, 67.6% +/- 2.9 and 55.2% +/- 0.3 after 3 months, respectively. Highest degradation was observed with NE at all the storage temperatures indicating even importance of the carrier structure.     

Solid lipid nanoparticles (SLN) for controlled drug delivery II. drug incorporation and physicochemical characterization

Solid lipid nanoparticles (SLN) are a colloidal carrier system for controlled drug delivery. The lipophilic model drugs tetracaine and etomidate were incorporated to study the maximum drug loading, entrapment efficacy, effect of drug incorporation on SLN size, zeta potential (charge) and long-term physical stability. Drug loads of up to 10% could be achieved whilst simultaneously maintaining a physically stable nanoparticle dispersion. Incorporation of drugs showed no or little effect on particle size and zeta potential compared to drug-free SLN. The optimized production parameters previously established for drug-free SLN dispersions can therefore be transferred to drug-loaded systems to facilitate product development.     

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations

Solid lipid nanoparticles (SLN) were developed at the beginning of the 1990 s as an alternative carrier system to emulsions, liposomes and polymeric nanoparticles. The paper reviews advantages-also potential limitations-of SLN for the use in topical cosmetic and pharmaceutical formulations. Features discussed include stabilisation of incorporated compounds, controlled release, occlusivity, film formation on skin including in vivo effects on the skin. As a novel type of lipid nanoparticles with solid matrix, the nanostructured lipid carriers (NLC) are presented, the structural specialties described and improvements discussed, for example, increase in loading capacity, physical and chemical long-term stability, triggered release and potentially supersaturated topical formulations. For both SLN and NLC, the technologies to produce the final topical formulation are described, especially the production of highly concentrated lipid nanoparticle dispersions >30-80% lipid content. Production issues also include clinical batch production, large scale production and regulatory aspects (e. g. status of excipients or proof of physical stability).     

Solid lipid nanoparticles (SLN) for controlled drug delivery. II. Drug incorporation and physicochemical characterization

Solid lipid nanoparticles (SLN) are a colloidal carrier system for controlled drug delivery. The lipophilic model drugs tetracaine and etomidate were incorporated to study the maximum drug loading, entrapment efficacy, effect of drug incorporation on SLN size, zeta potential (charge) and long-term physical stability. Drug loads of up to 10% could be achieved whilst simultaneously maintaining a physically stable nanoparticle dispersion. Incorporation of drugs showed no or little effect on particle size and zeta potential compared to drug-free SLN. The optimized production parameters previously established for drug-free SLN dispersions can therefore be transferred to drug-loaded systems to facilitate product development.     

Solid lipid nanoparticles for topical drug delivery

Solid lipid nanoparticles (SLN) have shown interesting potential as a drug delivery system for the topical delivery of various drugs. However, their performance when applied to the skin has not been fully investigated because of the complexity of their composition and structure. Theoretically, drug can be targeted systemically to the vasculature in the dermis, locally to the skin strata, or superficially to the surface of the skin. Therefore, the topical delivery vehicle should be designed according to the desired therapeutic purposes. To understand drug permeation behavior, it is essential to elucidate the pattern of drug release from the SLN formulations. A number of different drug release patterns have been outlined in the literature, and these patterns have been found to be related to the manufacturing process of the vehicle. In this paper, we summarize the results of SLN-mediated skin penetration data in the literature and illustrate several theoretical mechanisms of SLN-skin interactions that might take place at the site of action. Substantial research dedicated to the development of this promising drug delivery system is still required.     

Utilization of PEGylated cerosomes for effective topical delivery of fenticonazole nitrate: in-vitro characterization,statistical optimization,and in-vivo assessment

In this investigation, we focused on ceramide IIIB, a skin component whose depletion tends to augment multiple skin disorders and fungal infections. Ceramide IIIB was included into PEGylated surfactant-based vesicular phospholipid system to formulate ‘PEGylated cerosomes’ (PCs) loaded with fenticonazole nitrate (FTN). FTN is a potent antifungal agent adopted in the treatment of mixed mycotic and bacterial infections. The ceramide content of the vesicles may provide protective and regenerative skin activity whereas Brij^®; the PEGylated surfactant, can enhance drug deposition and skin hydration. Both components are expected to augment the topical effect of FTN. PCs were prepared by thin-film hydration technique. A 2³ full-factorial design was applied to study the effect of ceramide amount (X₁), Brij type (X₂) and Brij amount (X₃) on the physicochemical properties of the formulated PCs namely; entrapment efficiency (EE%;Y₁), particle size (PS;Y₂), polydispersity index (PDI;Y₃) and zeta potential (ZP;Y₄). The optimal formula was selected for further in-vivo dermatokinetic and histopathological study. The optimal FTN-loaded PC (PC6) showed nanosized cerosomes (551.60 nm) with high EE% (83.00%w/w), and an acceptable ZP value of 20.90 mV. Transmission electron micrographs of the optimal formula illustrated intertwined tubulation form deviated from the conventional spherical vesicles. Finally, the dermatokinetic study of PC6 showed higher drug concentration and localization of FTN in skin layers when compared with FTN suspension and the histopathological study confirmed its safety for topical application. The overall findings of our study verified the effectiveness of utilizing PEGylated cerosomes to augment the activity of FTN as a topical antifungal agent.     

A novel approach based on lipid nanoparticles (SLN) for topical delivery of alpha-lipoic acid

This study describes the development, preparation and characterization of solid lipid nanoparticles (SLN) containing the novel anti-ageing substance alpha-lipoic acid. Lipoic acid is chemically labile, i.e. the degradation products possess an unpleasant odour. Therefore, the active was encapsulated in SLN. A lipid with low melting point (Softisan 601) was selected for preparation of active-loaded SLN after screening the solubility of alpha-lipoic acid in physicochemically different lipids. An entrapment efficiency of 90% (UV analysis) was obtained for all developed formulations using Miranol Ultra C32 as emulsifying agent. Particle size stability was monitored during 3 months storing the samples at 20 degrees C and at 4 degrees C. Results of DSC analysis confirm that these systems are characterized by a solid-like behaviour, although with a very low crystallinity index.     

In-situ gel formulations of econazole nitrate: preparation and in-vitro and in-vivo evaluation

Objectives This study describes the in‐situ gelling of econazole nitrate containing thermosensitive polymers composed of poloxamer 407 and 188 as a novel treatment platform for vaginal candidiasis. Methods Aqueous thermosensitive formulations containing 1% of econazole nitrate and poloxamer 407 and/or 188 were prepared and their rheological, mechanical and drug‐release properties determined at 20 ± 0.1°C and/or 37 ± 0.1°C. Based on their biologically suitable thermorheological properties, formulations containing the mixtures of poloxamer 407 and 188 in ratios of 15:15 (F1), 15:20 (F2) and 20:10 (F3) were chosen for comprehensive analysis. Key findings Formulations based on F3 exhibited typical gel‐type mechanical spectra (G′ > G″) at 37°C whereas formulations based on F1 and F2 exhibited properties akin to weakly cross‐linked gels. Texture profile analysis demonstrated that F3 showed the highest cohesiveness, adhesiveness, hardness and compressibility. No statistically significant differences (P > 0.5) were observed in the release of econazole nitrate from the formulations at pH 4.5, which in all cases followed anomalous diffusion kinetics. Formulations based on 20% poloxamer 407:10% poloxamer 188 were chosen for in‐vivo studies and were shown to be effective for the treatment of the vaginal candidiasis. Histopathologic evaluation also supported the effectiveness of the thermosensitive formulation administered intravaginally. Conclusion By careful engineering of the rheological properties, in‐situ thermosensitive gel formulations of econazole nitrate were prepared and were shown to be efficacious in the treatment of vaginal candidiasis.     

Nanostructured lipid carriers (NLCs) versus solid lipid nanoparticles (SLNs) for topical delivery of meloxicam

Abstract

Objective: The aim of this study was to develop nanostructured lipid carriers (NLCs) as well as solid lipid nanoparticles (SLNs) and evaluate their potential in the topical delivery of meloxicam (MLX).

Materials and methods: The effect of various compositional variations on their physicochemical properties was investigated. Furthermore, MLX-loaded lipid nanoparticles-based hydrogels were formulated and the gels were evaluated as vehicles for topical application.

Results and discussion: The results showed that NLC and SLN dispersions had spherical shapes with an average size between 215 and 430?nm. High entrapment efficiency was obtained ranging from 61.94 to 90.38% with negatively charged zeta potential in the range of ?19.1 to ?25.7?mV. The release profiles of all formulations exhibited sustained release characteristics over 48?h and the release rates increased as the amount of liquid lipid in lipid core increased. Finally, Precirol NLC with 50% Miglyol® 812 and its corresponding SLN were incorporated in hydrogels. The gels showed adequate pH, non-Newtonian flow with shear-thinning behavior and controlled release profiles. The biological evaluation revealed that MLX-loaded NLC gel showed more pronounced effect compared to MLX-loaded SLN gel.

Conclusion: It can be concluded that lipid nanoparticles represent promising particulate carriers for topical application.     

Solid lipid nanoparticles as carriers for oral delivery of hydroxysafflor yellow A

Hydroxysafflor yellow A (HSYA) is the main bioactive flavonoid extracted from the flower of Carthamus tinctorius L., which is widely used in traditional Chinese medicine for the treatment of myocardial ischemia and cerebral ischemia. HSYA has high water solubility but poor intestinal membrane permeability, resulting in low oral bioavailability. Currently, only HSYA sodium chloride injection has been approved for clinical use and oral formulations are urgently needed. In this study, HSYA solid lipid nanoparticles (SLNs) with the structure of w/o/w were prepared by a warm microemulsion process using approved drug excipients for oral delivery to increase the oral absorption of HSYA. The optimized HSYA SLNs are spherical with an average size of 214 nm and the encapsulation efficiency is 55%. HSYA SLNs exhibited little cytotoxicity in Caco-2 and Hela cells, but increased the oral absorption of HSYA about 3.97-fold in rats, compared to HSYA water solution. In addition, cycloheximide pretreatment significantly decreased the oral absorption of HSYA delivered by SLNs. Importantly, the pharmacodynamics evaluation demonstrated that SLNs further decreased the infarct areas in rats. In conclude, SLNs could be a promising delivery system to enhance the oral absorption and pharmacological activities of HSYA.     

Solid lipid microparticles (SLM) containing juniper oil as anti-acne topical carriers: preliminary studies

Solid lipid microparticles (SLM) were used as carriers of juniper oil and proposed for the topical treatment of acne vulgare. The formulations were obtained by the o/w emulsification method. Compritol and Precirol were employed as lipidic materials. Emulsions containing 1.5% (w/w) of lipophilic phase (lipid and oil) and two different lipid to oil ratios (1:1 and 2:1) were prepared. Blank particles were also prepared, as a comparison. The SLM were characterized in terms of encapsulation efficiency, size, and morphology. The particle size stability in aqueous dispersions was monitored over one month. Evaporation of volatile compounds of oil from microparticles by weight loss was investigated. The qualitative composition of Juniper oil before and after the encapsulation process was determined by gas chromatography (GC) and gas chromatography/mass spectrum (GC/MS) analyses. The antimicrobial activity of the oil encapsulated into the lipid microparticles against P. acnes was studied as contact time assay and compared to the activity of the oil not encapsulated. The emulsification method here described was a good technique for the encapsulation of essential oils. Percentage yields of production and encapsulation efficiencies were higher for Compritol preparations than for these prepared using Precirol. All preparations were characterized by similar particle size distributions (dvs about 3-4 microm) regardless of lipid type and lipid to oil ratios. Microscopy observations showed that the microparticles in aqueous dispersions had almost spherical shape, independently from their composition. The scanning electron microscopy (SEM) analyses showed that when the particles were dried, they had an irregular shape and a rough surface. The SLM dispersions based on Compritol revealed particle size stability over the investigated period of 30 days. In contrast, an increase of the mean dimensions in the preparations containing Precirol was observed. A low loss of volatile oil compounds owing to evaporation from dry particles was found in all preparations. This indicated that the microparticles were able to substantially maintain the oil loaded inside their lipidic structure, reducing its volatility. Some modifications of composition were found in the oil encapsulated in SLM with respect to the juniper oil raw material, but these modifications did not decrease the antibacterial activity of the oil. The SLM here described are promising carriers for the development of anti-acne topical formulations containing Juniper oil.     

Preparation, characterization and physico-chemical properties of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC): their benefits as colloidal drug carrier systems

Solid lipid nanoparticles (SLN) have attracted increasing attention by various research groups and companies since the early 1990s. Their advantages over existing traditional carriers have been clearly documented. In addition, modified SLN have been described which are nanostructured lipid carriers (NLC) composed of liquid lipid blended with a solid lipid to form a nanostructured solid particle matrix. NLC combine controlled release characteristics with some advantages over SLN. This paper reviews the production techniques, characterization and physical stability of these systems including destabilizing factors and principles of drug loading, then considers aspects and benefits of SLN and NLC as colloidal drug carriers.     

Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs): recent advances in drug delivery

Solid lipid-based nanoparticles (SLBNs) were developed as potential alternatives to other conventional drug delivery systems such as polymeric nanoparticles, liposomes, and emulsions. In general, SLBNs are divided into two types: solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). SLNs are distinguishable from NLCs by the composition of solid particle matrix. SLBNs can be prepared by several methods including high pressure homogenization, solvent emulsification (or diffusion)-evaporation, and microemulsion technologies. Then, SLBNs can be characterized in terms of particle size distribution, surface charge, morphology, and crystallinity. SLBNs are well-tolerated and efficient carrier systems for parenteral, oral, inhalational, ocular, and dermal applications. This review provides an overview of the preparation and characterization technologies for SLBNs and focuses on recent advances in drug delivery using SLBNs.     

SEDDS of gliclazide: Preparation and characterization by in-vitro,ex-vivo and in-vivo techniques

In the study, self emulsifying drug delivery system (SEDDS) of gliclazide, a poorly soluble drug, was developed and evaluated by in-vitro, ex-vivo and in-vivo techniques. Oil and surfactant were screened out according to their solubilizing capacity. Among the tested components Transcutol HP and Tween-80 showed good solubilizing capacity. These two components were used in different ratios to prepare gliclazide SEDDS. The SEDDS formulations were transparent and clear. Droplet size of the emulsion was determined by Laser Diffraction Technology of Malvern. Formulation F1 containing 1:1 (m/m) mixture of Transcutol HP/Tween-80 showed minimum mean droplet size (50.959 μm). In-vitro drug release from F1 was higher (99% within 20 min) than other formulations. The developed SEDDS was also evaluated for ex-vivo permeability profile by using chicken intestinal sac. Formulation F1 showed optimal drug diffusion. In-vivo performance of SEDDS was evaluated in albino mice using plasma glucose level as a pharmacodynamic marker parameter. The test formulation (F1) showed significant reduction in plasma glucose level, after oral administration. So SEDDS may be an alternative technique for the oral administration of gliclazide.     

Preparation and characterization of n-dodecyl-ferulate-loaded solid lipid nanoparticles (SLN)

Solid lipid nanoparticles (SLN) containing a novel potential sunscreen n-dodecyl-ferulate (ester of ferulic acid) were developed. The preparation and stability parameters of n-dodecyl-ferulate-loaded SLN have been investigated concerning particle size, surface electrical charge (zeta potential) and matrix crystallinity. The chemical stability of n-dodecyl-ferulate at high temperatures was also assessed by thermal gravimetry analysis. For the selection of the appropriated lipid matrix, chemically different lipids were melted with 4% (m/m) of active and lipid nanoparticles were prepared by the so-called high pressure homogenization technique. n-Dodecyl-ferulate-loaded SLN prepared with cetyl palmitate showed the lowest mean particle size and polydispersity index, as well as the highest physical stability during storage time of 21 days at 4, 20 and 40 degrees C. These colloidal dispersions containing the sunscreen also exhibited the common melting behaviour of aqueous SLN dispersions.