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 (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) 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) 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.     

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)--a novel carrier for UV blockers.

The formulation of safe sunscreen products is of high importance due to their increasing use because of the diminishing ozone layer. Solid lipid nanoparticles (SLN) are introduced as the new generation of carriers for cosmetics, especially for UV blockers for the use on human skin and/or hair and production thereof is described. The crystalline cetylpalmitate SLN particles have the ability of reflecting and scattering UV radiation on their own thus leading to photoprotection without the need for molecular sunscreens. An in vitro assay showed that a placebo cetyl palmitate SLN formulation is twice to three times as potent in absorbing UV radiation as a conventional emulsion. Incorporation of sunscreens into SLN lead to a synergistic photoprotection, i.e. higher than the additive effect of UV scattering caused by the SLN and UV absorption by the sunscreen. The photoprotective effect after incorporation of the molecular sunscreen 2-hydroxy-4-methoxybenzophenone (Eusolex 4360) into the SLN dispersion was observed to be increased threefold compared to a reference emulsion. Further, film formation on the skin was investigated by scanning electron microscopy, showing particle fusion due to water evaporation and formation of a dense film.     

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.     

Solid lipid nanoparticles for ocular drug delivery

Ocular drug delivery remains challenging because of the complex nature and structure of the eye. Conventional systems, such as eye drops and ointments, are inefficient, whereas systemic administration requires high doses resulting in significant toxicity. There is a need to develop novel drug delivery carriers capable of increasing ocular bioavailability and decreasing both local and systemic cytotoxicity. Nanotechnology is expected to revolutionize ocular drug delivery. Many nano-structured systems have been employed for ocular drug delivery and yielded some promising results. Solid lipid nanoparticles (SLNs) have been looked at as a potential drug carrier system since the 1990s. SLNs do not show biotoxicity as they are prepared from physiological lipids. SLNs are especially useful in ocular drug delivery as they can enhance the corneal absorption of drugs and improve the ocular bioavailability of both hydrophilic and lipophilic drugs. SLNs have another advantage of allowing autoclave sterilization, a necessary step towards formulation of ocular preparations. This review outlines in detail the various production, characterization, sterilization, and stabilization techniques for SLNs. In-vitro and in-vivo methods to study the drug release profile of SLNs have been explained. Special attention has been given to the nature of lipids and surfactants commonly used for SLN production. A summary of previous studies involving the use of SLNs in ocular drug delivery is provided, along with a critical evaluation of SLNs as a potential ocular delivery system.     

Solid lipid nanoparticles for parenteral drug delivery

This review describes the use of nanoparticles based on solid lipids for the parenteral application of drugs. Firstly, different types of nanoparticles based on solid lipids such as "solid lipid nanoparticles" (SLN), "nanostructured lipid carriers" (NLC) and "lipid drug conjugate" (LDC) nanoparticles are introduced and structural differences are pointed out. Different production methods including the suitability for large scale production are described. Stability issues and drug incorporation mechanisms into the particles are discussed. In the second part, the biological activity of parenterally applied SLN and biopharmaceutical aspects such as pharmacokinetic profiles as well as toxicity aspects are reviewed.     

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 for targeted brain drug delivery

The present review discusses the potential use of solid lipid nanoparticles for brain drug targeting purposes. The state of the art on surfactant-coated poly(alkylcyanoacrylate) nanoparticles specifically designed for brain targeting is given by emphasizing the transfer of this technology to solid lipid matrices. The available literature on solid lipid nanoparticles and related carriers for brain drug targeting is revised as well. The potential advantages of the use of solid lipid nanoparticles over polymeric nanoparticles are accounted on the bases of a lower cytotoxicity, higher drug loading capacity, and best production scalability. Solid lipid nanoparticles physicochemical characteristics are also particularly regarded in order to address the critical issues related to the development of suitable brain targeting formulations. A critical consideration on the potential application of such technology as related to the current status of brain drug development is also given.     

Solid lipid nanoparticles for applications in gene therapy: a review of the state of the art

Importance of the field: Gene therapy represents a new paradigm in the prevention and treatment of many inherited and acquired diseases, including genetic disorders, such as cystic fibrosis, haemophilia and many somatic diseases, such as tumours, neurodegenerative diseases and viral infections, such as AIDS.

Areas covered in this review: Among a large array of non-viral transfection agents used for in-vitro applications, cationic SLNs are the topic of this review, being recently proposed as an alternative carrier for DNA delivery, due to many technological advantages such as large-scale production from substances generally recognized as safe, good storage stability and possibility of steam sterilization and lyophilisation.

What the reader will gain: The authors give some information on the knowledge of intracellular trafficking and SLNs-DNA complex chemical-physical properties reported until now in the literature.

Take home message: The future success of cationic SLNs for administration of genetic material will depend on their ability to efficiently cross the physiological barriers, selectively targeting a specific cell type in vivo and expressing therapeutic genes.     

Solid lipid nanoparticles as drug delivery systems

For a decade, trials have been made to utilize solid lipid nanoparticles (SLNs) as alternative drug delivery systems to colloidal drug delivery systems such as lipid emulsions, liposomes, and polymeric nanoparticles. Various lipid matrices, surfactants, and other excipients used in formulation, preparation methods, sterilization and lyophilization of SLNs are discussed in this article. Entrapment efficiency of drug carrier and its effect on physical parameters, drug release, and release mechanisms of various compositions are reviewed and discussed. Important points in characterization and stability of SLNs are outlined. Various in vitro studies carried out by different research groups are mentioned in addition to in vivo evaluation. Exploitation potential of SLNs to administer by various routes of administration are covered. Passive and active drug targeting using SLNs are presented.     

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 as a drug delivery system for peptides and proteins

Solid lipid particulate systems such as solid lipid nanoparticles (SLN), lipid microparticles (LM) and lipospheres have been sought as alternative carriers for therapeutic peptides, proteins and antigens. The research work developed in the area confirms that under optimised conditions they can be produced to incorporate hydrophobic or hydrophilic proteins and seem to fulfil the requirements for an optimum particulate carrier system. Proteins and antigens intended for therapeutic purposes may be incorporated or adsorbed onto SLN, and further administered by parenteral routes or by alternative routes such as oral, nasal and pulmonary. Formulation in SLN confers improved protein stability, avoids proteolytic degradation, as well as sustained release of the incorporated molecules. Important peptides such as cyclosporine A, insulin, calcitonin and somatostatin have been incorporated into solid lipid particles and are currently under investigation. Several local or systemic therapeutic applications may be foreseen, such as immunisation with protein antigens, infectious disease treatment, chronic diseases and cancer therapy.     

Cosmetic applications for solid lipid nanoparticles (SLN)

Solid lipid nanoparticles (SLN) are novel delivery systems for pharmaceutical and cosmetic active ingredients. This paper highlights advantages of SLN for cosmetic applications. The dependence of the occlusive effect on the particle size of SLN due to film formation is presented by in vitro data. An in vivo study showed that addition of 4% SLN to a conventional o/w cream lead to an increase of skin hydration of 31% after 4 weeks. The application of SLN as physical sunscreens and as active carriers for molecular sunscreens has also been investigated. The amount of molecular sunscreen could be decreased by 50% while maintaining the protection level compared to a conventional emulsion.     

PLGA nanoparticles in drug delivery: the state of the art

Nanoparticles represent drug delivery systems suitable for most administration routes. Over the years, a variety of natural and synthetic polymers have been explored for the preparation of nanoparticles, of which Poly(lactic acid) (PLA), Poly(glycolic acid) (PGA), and their copolymers (PLGA) have been extensively investigated because of their biocompatibility and biodegradability. Nanoparticles act as potential carries for several classes of drugs such as anticancer agents, antihypertensive agents, immunomodulators, and hormones; and macromolecules such as nucleic acids, proteins, peptides, and antibodies. The options available for preparation have increased with advances in traditional methods, and many novel techniques for preparation of drug-loaded nanoparticles are being developed and refined. The various methods used for preparation of nanoparticles with their advantages and limitations have been discussed. The crux of the problem is the stability of nanoparticles after preparation, which is being addressed by freeze-drying using different classes of lyoprotectants. Nanoparticles can be designed for the site-specific delivery of drugs. The targeting capability of nanoparticles is influenced by particle size, surface charge, surface modification, and hydrophobicity. Finally, the performance of nanoparticles in vivo is influenced by morphological characteristics, surface chemistry, and molecular weight. Careful design of these delivery systems with respect to target and route of administration may solve some of the problems faced by new classes of active molecules.     

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).