Solid Lipid Nanoparticles

The physico-chemical properties and in vivo efficacies of two nanoparticulate systems delivering the antiparkinsonian drug bromocriptine (BC) were compared in the present study. Monoolein Aqueous Dispersions (MADs) and Nanostructured Lipid Carriers (NLCs) were produced and characterized. Cryogenic transmission electron microscopy (cryo-TEM) and X-ray diffraction revealed the morphology of MAD and NLC. Dimensional distribution was determined by Photon Correlation Spectroscopy (PCS) and Sedimentation Field Flow Fractionation (SdFFF). In particular, BC was shown to be encapsulated with high entrapment efficiency both in MAD and in NLC, according to SdFFF combined with HPLC. Two behavioral tests specific for akinesia (bar test) or akinesia/bradykinesia (drag test) were used to compare the effects of the different BC formulations on motor disabilities in 6-hydroxydopamine hemilesioned rats in vivo, a model of Parkinson's disease. Both free BC and BC-NLC reduced the immobility time in the bar test and enhanced the number of steps in the drag test, although the effects of encapsulated BC were longer lasting (5 h). Conversely, BC-MAD was ineffective in the bar test and improved stepping activity in the drag test to a much lower degree than those achieved with the other preparations. We conclude that MAD and NLC can encapsulate BC, although only NLC provide long-lasting therapeutic effects possibly extending BC half-life in vivo.

The aim of this work was to characterize lipid nanoparticles from a rheological point of view, intended for drug delivery after parenteral administration. The conditions to obtain a re-dispersible powder using freeze-drying and spray-drying have also been investigated. Lipid nanoparticles (179.9 ± 6.2 nm) were prepared with the high pressure homogenization technique, using previously established optimal conditions (lipid volume fraction of 0.121), though particle size increased (285.9 ± 4.3 nm) in suspensions produced with higher lipid volume fractions (0.255). Rheology evidenced an expected increase of viscosity with the volume fraction and Newtonian behaviour was observed for volume fractions up to 0.161, while higher volume fractions showed shear thinning and shear thickening. In the suspension with a volume fraction of 0.255, a change of the complex modulus was observed at low shear stress. Freeze-drying and nano spray-drying were suitable only when trehalose was employed as an additive. In the former case, particle size was increased by 18% (198.7 ± 1.1 nm) using 20 fold water dilution. With spray-drying, the use of 20 fold dilution in water:ethanol (8:2) led to particle dimensions of 207.7 ±10.0 ( size 20%). In conclusion, cetylpalmitate nanoparticles seem to be suitable for parenteral application, up to volume fractions of 0.16, and pharmaceutical operations, which submit suspensions to shear stress, should not be a critical issue.

Nanospheres containing ketoprofen (Keto) and polymer eudragit RS were prepared using an emulsion solvent evaporation method. The ultrasonic probe (VCX500, vibracell) was used as a tool to disperse oil phase into aqueous phase leading to water/oil emulsion. Nanoparticles were successfully prepared and their morphologies and diameters were confirmed by transmission electron microscope (TEM) and dynamic light scattering (DLS), respectively. The result showed that particles were spherical with submicron size. The particle size was dependent on the RS concentration, emulsification tools and the types of organic solvents. For the encapsulation ability, Keto-loaded RS nanoparticle showed 9.8% of Keto in nanoparticle, which was evaluated by high-performance liquid chromatography (HPLC). Moreover, the drug release behavior of Keto-loaded eudragit RS nanoparticle was also investigated in vitro at pH 7.4 and compared to referential profenid.

The objective of this research is to formulate and evaluate Solid Lipid Nanoparticles containing Acyclovir by various phospholipids and surfactants using hot homogenization technique. Totally nine batches of SLN was formulated by hot homogenization technique and evaluates for PS,ZP,PI,Drug content, Entrapment efficiency, Invitro drug release studies and Invitro release kinetics studies. From the data's, it was concluded that hot homogenization technique method followed by ultrasonication was an optimized technique for the preparation of SLN nanoparticles containing Acyclovir, which lead to better results like high entrapment efficiency, high drug content and SLS was a better choice of surfactant to reduce the particle size and leads to uniform distribution of SLN in its phase. So, SLN will be an alternative drug delivery system for acyclovir to enhance the bioavailability and therapeutic response of drug.

Nanoscale drug delivery systems using liposomes and nanoparticles are emerging technologies for the rational delivery of chemotherapeutic drugs in the treatment of cancer. Their use offers improved pharmacokinetic properties, controlled and sustained release of drugs and, more importantly, lower systemic toxicity. The commercial availability of liposomal Doxil W and albumin-nanoparticle-based Abraxane W has focused attention on this innovative and exciting field. Recent advances in liposome technology offer better treatment of multidrugresistant cancers and lower cardiotoxicity. Nanoparticles offer increased precision in chemotherapeutic targeting of prostate cancer and new avenues for the treatment of breast cancer. Here we review current knowledge on the two technologies and their potential applications to cancer treatment.

Burst release as well as sustained release has been reported for SLN suspensions. For dermal application, both features are of interest. Burst release can be useful to improve the penetration of a drug. Sustained release becomes important with active ingredients that are irritating at high concentrations or to supply the skin over a prolonged period of time with a drug. Glyceryl behenate SLN were loaded with vitamin A and the release profiles were studied. Franz diffusion cells were used to assess the release kinetic over a period of 24 h. Within the first 6 h retinol SLN displayed controlled release. After longer periods (12-24 h) the release rate increased and even exceeded the release rate of comparable nanoemulsions. Pure SLN dispersions are characterised by low viscosity. In contrast to membranous vesicles, SLN can also be stably incorporated in convenient topical dosage forms like hydrogels or creams. In the Franz diffusion cell these preparations showed a controlled release over 12-18 h. Similar to SLN dispersions an increase in release rate over a 24-h period was found. A good correlation between polymorphic transitions and increased drug release was observed in this study. Sustained release was often related to the metastable b9 polymorph. Drug expulsion is explained by a reduction of amorphous regions in the carrier lattice due to a b9→b polymorphic transition. This transformation can be controlled with surfactant mixtures or, in the case i of the hydrogel and oil / water cream, with humectants or gelling agents. Thus, the release rate for the topical route of application is adjustable.

Solid lipid nanoparticles (SLN) introduced in 1991 represent an alternative carrier system to traditional colloidal carriers, such as emulsions, liposomes and polymeric micro-and nanoparticles. SLN combine advantages of the traditional systems but avoid some of their major disadvantages. This paper reviews the present state of the art regarding production techniques for SLN, drug incorporation, loading capacity and drug release, especially focusing on drug release mechanisms. Relevant issues for the introduction of SLN to the pharmaceutical market, such as status of excipients, toxicity/tolerability aspects and sterilization and long-term stability including industrial large scale production are also discussed. The potential of SLN to be exploited for the different administration routes is highlighted. References of the most relevant literature published by various research groups around the world are provided. q

Nanoscale drug delivery systems using liposomes and nanoparticles are emerging technologies for the rational delivery of chemotherapeutic drugs in the treatment of cancer. Their use offers improved pharmacokinetic properties, controlled and sustained release of drugs and, more importantly, lower systemic toxicity. The commercial availability of liposomal Doxil W and albumin-nanoparticle-based Abraxane W has focused attention on this innovative and exciting field. Recent advances in liposome technology offer better treatment of multidrugresistant cancers and lower cardiotoxicity. Nanoparticles offer increased precision in chemotherapeutic targeting of prostate cancer and new avenues for the treatment of breast cancer. Here we review current knowledge on the two technologies and their potential applications to cancer treatment.

tSolid lipid nanoparticles (SLN) composed of long-chain fatty acids (palmitic acid, stearic acid or arachidicacid), Epikuron 200 (purified phosphatidylcholine), and bile salts (cholate, taurocholate or taurodeoxy-cholate) have been prepared by dilution of a microemulsion. A total of five different systems wereprepared, and characterized by photon correlation spectroscopy, transmission electron microscopy,differential scanning calorimetry, and infrared spectroscopy. The SLN formulation showing optimal prop-erties (lowest size and polydispersity index and highest zeta potential) was obtained with stearic acidand taurodeoxycholate as cosurfactant. This formulation was loaded with Calendula officinalis extract, anatural compound used on ophthalmic formulations given its anti-inflammatory, emollient, and woundrepairing activity. Calendula-loaded SLN preparations were characterized in order to determine loadingcapacity and entrapment efficiency. In vitro cytotoxicity and wound healing efficacy of Calendula-loadedSLN compared to that of a free plant extract were evaluated on a conjunctival epithelium cell line WKD.Our results suggest that this SLN formulation is a safe and solvent-free Calendula extract delivery sys-tem which could provide a controlled therapeutic alternative for reducing disease-related symptoms andimproving epithelium repair in ocular surface.

Lipid-based oral drug delivery Lipase activity Lymphatic uptake Bioavailability enhancement Solid dosage form Adsorption Lipid digestion products In vitro lipolytic model In vitro-in vivo correlation Solid lipid nanoparticles a b s t r a c t

Skin is a widely used route of delivery for local and systemic drugs and is potentially a route for their delivery as nanoparticles. The skin provides a natural physical barrier against particle penetration, but there are opportunities to deliver therapeutic nanoparticles, especially in diseased skin and to the openings of hair follicles. Whilst nanoparticle drug delivery has been touted as an enabling technology, its potential in treating local skin and systemic diseases has yet to be realised. Most drug delivery particle technologies are based on lipid carriers, i.e. solid lipid nanoparticles and nanoemulsions of around 300 nm in diameter, which are now considered microparticles. Metal nanoparticles are now recognized for seemingly small drug-like characteristics, i.e. antimicrobial activity and skin cancer prevention. We present our unpublished clinical data on nanoparticle penetration and previously published reports that support the hypothesis that nanoparticles N 10 nm in diameter are unlikely to penetrate through the stratum corneum into viable human skin but will accumulate in the hair follicle openings, especially after massage. However, significant uptake does occur after damage and in certain diseased skin. Current chemistry limits both atom by atom construction of complex particulates and delineating their molecular interactions within biological systems. In this review we discuss the skin as a nanoparticle barrier, recent work in the field of nanoparticle drug delivery to the skin, and future directions currently being explored.

Background: Topical drug administration offers an attractive route with minimal invasiveness. It also avoids limitations of intravenous administration such as the first pass metabolism and presystemic elimination within the gastrointestinal tract. Furthermore, topical drug administration is safe, have few side effects, is easy to apply, and offers a fast onset of action. However, the development of effective topical formulations still represents a challenge for the desired effect to be reached, locally or systemically. Solid lipid nanoparticles and nanos-tructured lipid carriers are particular candidates to overcome the problem of topical drug administration. The nanometric particle size of lipid nanoparticles favors the physical adhesion to the skin or mucosal, what can also be attained with the formation of hybrid (nanoparticles/polymer) systems. Methods: In this review, we discuss the major challenges for lipid nanoparticles formulations for topical application to oral mucosa, skin, and eye, highlighting the strategies to improve the performance of lipid nanoparticles for topical applications. Next, we critically analyzed the in vitro and in vivo approaches used to evaluate lipid nanoparticles performance and toxicity. Conclusion: We addressed some major drawbacks related to lipid nanoparticle topical formulations and concluded the key points that have to be overcome to help them to reach the market in topical formulations to oral mucosa, skin, and eye.

The main aim of pharmaceutical technology research is the design of successful formulations for effective therapy, taking into account several issues including therapeutic requirements and patient compliance. In this regard, several achievements have been reported with colloidal carriers, in particular with lipid nanoparticles, due to their unique physicochemical properties. For several years these carriers have been showing potential success for several administration routes, namely oral, dermal, parenteral, and, more recently, for pulmonary and brain targeting. The present chapter provides a review of the use of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) to modify the release profile and the pharmacokinetic parameters of active pharmaceutical ingredients (APIs) incorporated in these lipid matrices, aiming to modify the API bioavailability, either upwards or downwards depending on the therapeutic requirement. Definitions of the morphological characteristics, surface properties, and polymorphic structures will also be given, emphasizing their influence on the incorporation parameters of the API, such as yield of production, loading capacity, and encapsulation efficiency.

Several scientific hurdles still have to be overcome before gene therapy becomes a reality. One of them is the development of safe and efficient gene delivery system. Here, we have employed factorial design to optimize the production of solid lipid nanoparticles (SLN) for gene delivery. A 2×3 full-factorial experimental design was used for the optimization of SLNs formulations. The variables were defined by the components of the formulation: concentration of stearic acid, DOTAP, and Pluronic F68 at two levels (−1, 1) and 3 central points (0). Different SNL formulations were prepared by varying the amount of components and several properties were tested, including their capacity to accommodate DNA and protection against DNase degradation, colloidal stability, in vitro cytotoxicity, and transfection efficiency in prostate cancer cells. Finally, response Surface Methodology was used to select the most effective formulation for gene delivery to prostate cancer cells in vitro. In conclusion, this study revealed that stearic acid and Pluronic F68 were determinant to SLN size and stability, respectively, while small amounts of DOTAP are essential for a successful transfection.

Solid lipid nanoparticles (SLNs) have attracted increasing attention during recent years. Due to their unique size dependent properties, lipid nanoparticles offer possibilities to develop new therapeutics. The ability to incorporate drugs into nanoparticles offers a new prototype in drug delivery thus realizing the dual goal of both controlled release and site-specific drug delivery. Drug delivery to the skin is widely used for local and systemic delivery and has potential to be improved by application of nanoparticulate formulations. If investigated appropriately, solid lipid nanoparticles may open new opportunities in therapy of complex diseases which is difficult to treat.

Nanotechnology is rapidly expanding research area, encompassing the development of man-made materials in nanometer size range. Nanoscale drug delivery system using various nanomaterials is emerging technology for the rational delivery of many chemotherapeutic agents. Nanoparticles attracted the scientists across many disciplines to engineer many desired properties that might otherwise be incompatible on a single device. Formulation scientists are facing the challenges such as poor solubility and bioavailability of the newly invented drugs. One of the approaches to face the above challenge is to develop the particulate carrier system. Solid lipid nanoparticle or liposphere or nanosphere system is the most feasible particulate carrier system which is an alternative to nanoemulsions, liposomes and polymeric nanoparticles. This system offers added advantages in comparison to other related particulate drug delivery systems. The present review emphasizes on various basic and applied aspects of solid lipid nanoparticles in novel drug delivery system especially techniques involved in their production, characterization and various applications. It also focuses on the drug loading capacity, drug incorporation and factors affecting drug release from this colloidal system.

Solid lipid nanoparticles (SLN) introduced in 1991 represent an alternative carrier system to traditional colloidal carriers, such as emulsions, liposomes and polymeric micro-and nanoparticles. SLN combine advantages of the traditional systems but avoid some of their major disadvantages. This paper reviews the present state of the art regarding production techniques for SLN, drug incorporation, loading capacity and drug release, especially focusing on drug release mechanisms. Relevant issues for the introduction of SLN to the pharmaceutical market, such as status of excipients, toxicity/tolerability aspects and sterilization and long-term stability including industrial large scale production are also discussed. The potential of SLN to be exploited for the different administration routes is highlighted. References of the most relevant literature published by various research groups around the world are provided. q

Solid lipid nanoparticles (SLNs) have been proposed in the 1990s as appropriate drug delivery systems, and ever since they have been applied in a wide variety of cosmetic and pharmaceutical applications. In addition, SLNs are considered suitable alternatives as carriers in gene delivery. Although important advances have been made in this particular field, fundamental knowledge of the underlying mechanisms of SLN-mediated gene delivery is conspicuously lacking, an imperative requirement in efforts aimed at further improving their efficiency. Here, we address recent advances in the use of SLNs as platform for delivery of nucleic acids as therapeutic agents. In addition, we will discuss available technology for conveniently producing SLNs. In particular, we will focus on underlying molecular mechanisms by which SLNs and nucleic acids assemble into complexes and how the nucleic acid cargo may be released intracellularly. In discussing underlying mechanisms, we will, when appropriate, refer to analogous studies carried out with systems based on cationic lipids and polymers, that have proven useful in the assessment of structure–function relationships. Finally, we will give suggestions for improving SLN-based gene delivery systems, by pointing to alternative methods for SLNplex assembly, focusing on the realization of a sustained nucleic acid release.

As drug delivery systems Nanoparticulate widely investigated because of many advantages such as smaller size, controlled drug release potential, targeting ability, enhancement of therapeutic efficacy and reduction of toxicity. So, Solid Lipid Nanoparticles have recently received considerable attention as alternative drug delivery carrier. In this study Solid Lipid Nanoparticles (SLNs) containing tamoxifen, nonsteroidal antiestrogens have been loaded and to be used as breast cancer therapy, were prepared by hot High Pressure Homogenization techniques. Tamoxifen loaded SLNs seem to have dimensional properties useful for parenteral administration. Preliminary study of antiproliferative activity in vitro, carried out on MCF-7 cell line (human breast cancer cells), demonstrated that SLNs, containing tamoxifen showed an antitumoral activity comparable to free drug. Tamoxifen loaded SLNs seem to have dimensional properties useful for parenteral administration. SLN was characterized by Differential Scanning Calorimetery (DSC), Transmission Electron Microscopy (TEM), Zeta Potential and Particle Size. The results of characterization studies strongly support the potential application of Tamoxifen-loaded SLNs as a carrier system. The SLN presented here are well suited for certain drug delivery applications, particularly breast cancer therapy.

Background : The skin is the largest organ of our body and acts as a protective barrier with sensory and immunological functions. Its peculiar structure influences the passage of bioactives and only its modulation can facilitate the drug dermal/transdermal diffusion. In the past few years research in this field has assured better use of this application area. Methods : One of the most promising approaches is the use of drug delivery devices; this review explains the state of the art of drug transport through the skin by means of vesicular (classic liposomes, Transfersomes, niosomes and ethosomes) and particulate systems. Results/conclusion : Colloidal drug delivery systems are important in the field of drug delivery systems as their different characteristics make them suitable for various purposes.

The aim of this study was to develop biocompatible lipid-based nanocarriers for retinyl palmitate (RP) to improve its skin delivery, photostability and biocompatibility, and to avoid undesirable topical side effects. RP loaded nanoemulsions (NEs), liposomes (LPs) and solid lipid nanoparticles (SLNs) were characterized in terms of size, surface electrical charge, pH, drug encapsulation efficiency and morphology. Spherical-shaped nanocarriers with a negatively charged surface (>|40| mV) and mean size lower than 275 nm were produced with adequate skin compatibility. The rheological properties showed that aqueous dispersions of SLNs followed a non-Newtonian behavior, pseudoplastic fluid adjusted to Herschel-Bulkley equation, whereas LPs and NEs exhibited a Newtonian behavior. SLNs offered significantly better photoprotection than LPs and NEs for RP. The cumulative amount of drug permeated through human skin at the end of 38 h was 6.67 AE 1.58 mg, 4.36 AE 0.21 mg and 3.64 AE 0.28 mg for NEs, LPs and SLNs, respectively. NEs flux was significantly higher than SLNs and LPs: NEs (0.37 AE 0.12 mg/h) > LPs (0.15 AE 0.09 mg/h) > SLNs (0.10 AE 0.05 mg/h). LPs offered significant higher skin retention than NEs and SLNs. Finally, even though all developed nanocarriers were found to be biocompatible, according to histological studies, NE was the system that most disrupted the skin. These encouraging findings can guide in proper selection of topical carriers among the diversity of available lipid-based nanocarriers, especially when a dermatologic or cosmetic purpose is desired.

Brain is a delicate organ, isolated from general circulation and characterized by the presence of relatively impermeable endothelial cells with tight junctions, enzymatic activity and the presence of active efflux transporter mechanisms (like P-gp efflux). These formidable obstacles often impede drug delivery to the brain. As a result several promising molecules (showing a good potential in in vitro evaluation) are lost from the market for a mere consequence of lack of in vivo response probably because the molecule cannot reach the brain in a sufficient concentration. The options to tailor make molecules for brain, though open to the medical chemist, are a costly proposition in terms of money, manpower and time (almost 50 years). The premedial existing approaches for brain delivery like superficial and ventricular application of chemical or the application of chemicals to brain parenchyma are invasive and hence are less patient friendly, more laborious and require skill and could also damage the brain permanently. In view of these considerations novel drug delivery systems such as the nanoparticles are presently being explored for their suitability for targeted brain delivery.

Despite the fact that we live in an era of advanced technology and innovation, infectious diseases, like malaria, continue to be one of the greatest health challenges worldwide. The main drawbacks of conventional malaria chemotherapy are the development of multiple drug resistance and the non-specific targeting to intracellular parasites, resulting in high dose requirements and subsequent intolerable toxicity. Nanosized carriers have been receiving special attention with the aim of minimizing the side effects of drug therapy, such as poor bioavailability and the selectivity of drugs. Several nanosized delivery systems have already proved their effectiveness in animal models for the treatment and prophylaxis of malaria. A number of strategies to deliver antimalarials using nanocarriers and the mechanisms that facilitate their targeting to Plasmodium spp.-infected cells are discussed in this review. Taking into account the peculiarities of malaria parasites, the focus is placed particularly on lipid-based (e.g., liposomes, solid lipid nanoparticles and nano and microemulsions) and polymer-based nanocarriers (nanocapsules and nanospheres). This review emphasizes the main requirements for developing new nanotechnology-based carriers as a promising choice in malaria treatment, especially in the case of severe cerebral malaria.

The present review compiles the applications of lipid nanoparticles mainly solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and lipid drug conjugates (LDC) in parenteral delivery of pharmaceutical actives. The attempts to incorporate anticancer agents, imaging agents, antiparasitics, antiarthritics, genes for transfection, agents for liver, cardiovascular and central nervous system targeting have been summarized. The utility of lipid nanoparticles as adjuvant has been discussed separately. A special focus of this review is on toxicity caused by these kinds of lipid nanoparticles with a glance on the fate of lipid nanoparticles after their parenteral delivery in vivo viz the protein adsorption patterns.

Neuroinflammation is a prominent feature of Alzheimer disease (AD) and other chronic neurodegenerative disorders. Intracerebroventricular (ICV) streptozotocin (STZ) induced-cognitive impairment has been widely used as an experimental paradigm of Alzheimer's disease. Sesamol is a potent inhibitor of cytokine production as well as an antioxidant. The present study was designed to evaluate the effectiveness of sesamol in ICV-STZ-induced cognitive deficits in rats by incorporating it into solid lipid nanoparticles (SLNs). ICV-STZ administration produced significant cognitive deficits as assessed by both Morris water maze and elevated plus maze task which is accompanied by significantly enhanced nitrodative stress, altered acetylcholinesterase in rat brain along with significantly increased serum TNFα levels. Chronic treatment with sesamol and sesamol loaded SLNs dose dependently restored cognitive deficits in ICV-STZ rats along with mitigation of nitrodative stress and cytokine release. Effectiveness of SLNs to deliver sesamol to the brain was shown by a significantly better alleviation of the oxidative stress parameters. Our findings demonstrate that loading of sesamol in SLNs is an effective strategy to mitigate ICV-STZ-induced neuronal dysfunction and memory deficits.

Nanotechnology is rapidly expanding research area, encompassing
the development of man-made materials in nanometer size range.
Nanoscale drug delivery system using various nanomaterials is
emerging technology for the rational delivery of many
chemotherapeutic agents. Nanoparticles attracted the scientists
across many disciplines to engineer many desired properties that
might otherwise be incompatible on a single device. Formulation
scientists are facing the challenges such as poor solubility and
bioavailability of the newly invented drugs. One of the approaches
to face the above challenge is to develop the particulate carrier
system. Solid lipid nanoparticle or liposphere or nanosphere
system is the most feasible particulate carrier system which is an
alternative to nanoemulsions, liposomes and polymeric
nanoparticles. This system offers added advantages in comparison
to other related particulate drug delivery systems. The present
review emphasizes on various basic and applied aspects of solid
lipid nanoparticles in novel drug delivery system especially
techniques involved in their production, characterization and
various applications. It also focuses on the drug loading capacity,
drug incorporation and factors affecting drug release from this
colloidal system

To develop and characterize solid lipid nanoparticle (SLN) systems containing dextran sulfate or sodium alginate as anionic polymers for the delivery of clindamycin phosphate as a model hydrophilic cationic drug. Methods: A multi-level factorial design was used for the preparation and optimization of clindamycin SLNs. Polymers (dextran sulfate and sodium alginate), Tween 80, and Pluronic F68 were chosen as the independent variables. The SLNs were prepared using stearic acid as the lipid matrix by an emulsion congealing technique with cold homogenization. Particle size and drug loading were evaluated as the primary responses. The morphology and drug release rate of the selected formulations were also determined.

The aim of this study was to formulate a new delivery system for ecological pesticides by the incorporation of Artemisia arborescens L essential oil into solid lipid nanoparticles (SLN). Two different SLN formulations were prepared following the high-pressure homogenization technique using Compritol 888 ATO as lipid and Poloxamer 188 or Miranol Ultra C32 as surfactants. The SLN formulation particle size was determined using Photon correlation spectroscopy (PCS) and laser diffraction analysis (LD). The change of particle charge was studied by zeta potential (ZP) measurements, while the melting and recrystallization behavior was studied using differential scanning calorimetry (DSC). In vitro release studies of the essential oil were performed at 35°C. Data showed a high physical stability for both formulations at various storage temperatures during 2 months of investigation. In particular, average diameter of Artemisia arborescens L essential oil-loaded SLN did not vary during storage and increased slightly after spraying the SLN dispersions. In vitro release experiments showed that SLN were able to reduce the rapid evaporation of essential oil if compared with the reference emulsions. Therefore, obtained results showed that the studied SLN formulations are suitable carriers in agriculture.

For the development of an optimized oral formulation for cyclosporine A, 2% of this drug has been formulated in solid lipid nanoparticles (SLN TM , mean size 157 nm) and as nanocrystals (mean size 962 nm). The encapsulation rate of SLN was found to be 96.1%. Nanocrystals are composed of 100% of drug. For the assessment of the pharmacokinetic parameters the developed formulations have been administered via oral route to three young pigs. Comparison studies with a commercial Sandimmun Neoral/Optoral ® used as reference have been performed. The blood profiles observed after oral administration of the commercial microemulsion Sandimmun ® revealed a fast absorption of drug leading to the observation of a plasma peak above 1000 ng/ml within the first 2 h. For drug nanocrystals most of the blood concentrations were in the range between 30 and 70 ng/ml over a period of 14 h. These values were very low, showing huge differences between the measuring time points and between the tested animals. On the contrary, administration of cyclosporine-loaded SLN led to a mean plasma profile with almost similarly low variations in comparison to the reference microemulsion, however with no initial blood peak as observed with the Sandimmun Neoral/Optoral ® . Comparing the area under the curves (AUC) obtained with the tested animals it could be stated that the SLN TM formulation avoids side effects by lacking blood concentrations higher than 1000 ng/ml. In this study it has been proved that using SLN TM as a drug carrier for oral administration of cyclosporine A a low variation in bioavailability of the drug and simultaneously avoiding the plasma peak typical of the first Sandimmun ® formulation can be achieved.

Amphotericin B (BCS-Class IV) is the major treatment available against the fatal infection of Visceral
leishmaniasis. Conventional chemotherapy of AMB is challenging because of its severe and potentially
lethal side-effects i.e., nephrotoxicity and hepatotoxicity. Therefore, there is an urgent need
of designing novel, leishmanicidal drug carriers for safe and effective management of VL. Colloidal
carriers like liposomes, niosomes and emulsomes offer better therapeutic efficacy over the conventional
treatment with reduced side effects and toxicity but suffer with the stability problem. Lipid
nanoparticles are stable, biodegradable, biocompatible carrier offering excellent therapeutic efficacy.
Here, an effort has been made to prepare novel nanostructured lipid carriers of AMB to increase
therapeutic efficacy and reduced toxicity with the use of microfluidizer. Different formulations were
prepared and optimized by varying pressure and number of cycles. Formulations were selected
for further studies on the basis of particle size and particle size distribution. The drug entrapment
efficiency was achieved up to 90.1% with particle size 148±2
7 nm of the formulation and zeta
potential of −30±1
8 mv. The optimized formulation was found stable for more than 6 months in
terms of particle size and size distribution. The characterization of the formulation was done using
Scanning Electron Microscopy and Transmission Electron Microscopy. The in vitro release profile
of the AMB loaded NLCs showed 65% drug release within 24 hours. The optimized formulations
were found within the permissible range of haemolysis and cytotoxicity. The findings suggested that
it would be preferable to deliver AMB through nanostructured lipid carriers.
Keywords: Visceral Leishmaniasis, Amphotericin B, Microfluidizer, Lipid Nanoparticles

A B S T R A C T Myricetin-a natural flavonoid-has attracted a great interest due to its antioxidant and free-radical scavenging potential. However, its physicochemical instability critically impairs its dosage form design, evaluation and administration. In an attempt to protect from degradation, MYR was encapsulated into Gelucire-based solid lipid nanoparticles (SLNs). The impact of medium pH, processing temperature and different additives on the drug degradation either in free or nanoencapsulated form was assessed. MYR stability was further monitored in essential biorelevant fluids. Investigations have led to the recommendation that the presence of fat-soluble antioxidant is necessary during SLN preparation to protect the drug at high temperature. Meanwhile, physiological buffers as well as simulated fluids should be supplemented with stabilizers as tween 80 and Poloxamer 407, in addition to water-soluble antioxidant such as sodium sulfite. Interestingly, mucin-containing fluids are suggested to provide better protection to MYR, in contrast, cell culture media do not guarantee MYR stability. The degradation kinetics changed from 1st to 2nd order mechanism after MYR nanoencapsulation. In presence of the aforementioned additives, MYR-SLNs significantly reduced the drug degradation rate constant up to 300-folds and prolonged the half-life time up to 4500-folds compared to free MYR in physiological buffers (One-way ANOVA, p < 0.05). As a proof of concept, in vitro release experiment in presence of phosphate buffer (pH 7.4) supplemented with these additives ensured sustained release of MYR over > 8 h with no signs of degradation. The study emphasizes virtuous guidance regarding appropriate nanoencapsulation conditions and evaluation attributes ensuing MYR physicochemical stability.

The clinical use of ketoconazole has been related to some adverse effects in healthy adults, specially local reactions, such as severe irritation, pruritus and stinging. The purpose of the present work is the assessment of ketoconazole stability in aqueous SLN and NLC dispersions, as well as the physicochemical stability of these lipid nanoparticles, which might be useful for targeting this drug into topical route, minimizing the adverse side effects and providing a controlled release. Lipid particles were prepared using Compritol Õ 888 ATO as solid lipid. The natural antioxidant -tocopherol was selected as liquid lipid compound for the preparation of NLC. Ketoconazole loading capacity was identical for both SLN and NLC systems (5% of particle mass). SLN were physically stable as suspensions during 3 months of storage, but the SLN matrix was not able to protect the chemically labile ketoconazole against degradation under light exposure. In contrast, the NLC were able to stabilize the drug, but the aqueous NLC dispersion showed size increase during storage. Potential topical formulations are light-protected packaged SLN or NLC physically stabilized in a gel formulation.

Delivering chemotherapeutics by nanoparticles into tumor is impeded majorly by two factors: nonspecific targeting and inefficient penetration. Targeted delivery of anti-cancer agents solely to tumor cells introduces a smart strategy because it enhances the therapeutic index compared with untargeted drugs. The present study was performed to investigate the efficiency of adenosine (ADN) to target solid lipid nanoparticles (SLN) to over expressing adenosine receptor cell lines such as human breast cancer and prostate cancer (MCF-7 and DU-145 cells), respectively. SLN were prepared by emulsification and solvent evaporation process using docetaxel (DTX) as drug and were characterized by various techniques like dynamic light scattering, differential scanning calorimeter and transmission electron microscopy. DTX loaded SLNs were surface modified with ADN, an adenosine receptors ligand using carbodiimide coupling. Conjugation was confirmed using infrared spectroscopy and quantified using phenol–sulfuric acid method. Conjugated SLN were shown to have sustained drug release as compared to unconjugated nanoparticles and drug suspension. Compared with free DTX and unconjugated SLN, ADN conjugated SLN showed significantly higher cytotoxicity of loaded DTX, as evidenced by in vitro cell experiments. The IC50 was 0.41mg/ml for native DTX, 0.30mg/ml for unconjugated SLN formulation, and 0.09mg/ml for ADN conjugated SLN formulation in MCF-7 cell lines. Whereas, in DU-145, there was 2 fold change in IC50 of ADN–SLN as compared to DTX. IC50 was found to be 0.44mg/ml for free DTX, 0.39mg/ml for unconjugated SLN and 0.22mg/ml for ADN–SLN. Annexin assay and cell cycle analysis assay further substantiated the cell cytotoxicity. Fluorescent cell uptake and competitive ligand-receptor binding assay corroborated the receptor mediated endocytosis pathway indicated role of adenosine receptors in internalization of conjugated particles. Pharmacokinetic studies of lipidic formulations depicted significant improvement in pharmacokinetic parameters than marketed formulation. ADN conjugated SLN proved to be an efficient drug delivery vehicle. Hence, ADN can be used as a potential ligand to target breast and prostate cancer.Delivering chemotherapeutics by nanoparticles into tumor is impeded majorly by two factors: nonspecific targeting and inefficient penetration. Targeted delivery of anti-cancer agents solely to tumor cells introduces a smart strategy because it enhances the therapeutic index compared with untargeted drugs. The present study was performed to investigate the efficiency of adenosine (ADN) to target solid lipid nanoparticles (SLN) to over expressing adenosine receptor cell lines such as human breast cancer and prostate cancer (MCF-7 and DU-145 cells), respectively. SLN were prepared by emulsification and solvent evaporation process using docetaxel (DTX) as drug and were characterized by various techniques like dynamic light scattering, differential scanning calorimeter and transmission electron microscopy. DTX loaded SLNs were surface modified with ADN, an adenosine receptors ligand using carbodiimide coupling. Conjugation was confirmed using infrared spectroscopy and quantified using phenol–sulfuric acid method. Conjugated SLN were shown to have sustained drug release as compared to unconjugated nanoparticles and drug suspension. Compared with free DTX and unconjugated SLN, ADN conjugated SLN showed significantly higher cytotoxicity of loaded DTX, as evidenced by in vitro cell experiments. The IC50 was 0.41mg/ml for native DTX, 0.30mg/ml for unconjugated SLN formulation, and 0.09mg/ml for ADN conjugated SLN formulation in MCF-7 cell lines. Whereas, in DU-145, there was 2 fold change in IC50 of ADN–SLN as compared to DTX. IC50 was found to be 0.44mg/ml for free DTX, 0.39mg/ml for unconjugated SLN and 0.22mg/ml for ADN–SLN. Annexin assay and cell cycle analysis assay further substantiated the cell cytotoxicity. Fluorescent cell uptake and competitive ligand-receptor binding assay corroborated the receptor mediated endocytosis pathway indicated role of adenosine receptors in internalization of conjugated particles. Pharmacokinetic studies of lipidic formulations depicted significant improvement in pharmacokinetic parameters than marketed formulation. ADN conjugated SLN proved to be an efficient drug delivery vehicle. Hence, ADN can be used as a potential ligand to target breast and prostate cancer.

The present study has been focused on determination and evaluation of three different preparation techniques, i.e., solvent-diffusion, hot homogenization-ultrasonification and microemulsification, applied in fabrication of biocompatible phosphatidylcholine solid lipid nanoparticles ((PC)-SLNs), containing Polawax National Formulary (NF) in the internal lipid phase. The fabricated lipid nanoparticles were loaded with the newly synthesized flavonoid cocrystals, i.e., baicalein–nicotinamide (1:1) (BaiNam), myricetin–piracetam (1:1) (MyrPac) and myricetin–caffeine (1:1) (MyrCaf) cocrystals in relation to the starting flavonoids, differing in solubility and physical state. The assessment of all studied drugs entrapment and availability in aqueous SLN dispersions has been carried out; the size along with size distribution of lipid nanoparticles loaded with the studied flavonoids cocrystals and flavonoids was determined by the DLS technique, while the structural changes—by FT-IR spectroscopy and X-ray powder diffraction (XRPD) of the lipid nanomatrices. XRPD and FT-IR analyses confirmed that parent flavonoids as well as their cocrystals are present in the nanoparticles fabricated with solvent-diffusion method as physical mixtures with the lipid and their crystalline structures at least partially conserved. Summarizing, we designed and fabricated the biocompatible SLN-type nanocarriers of enhanced physical stability and availability for the flavonoids delivery—a vast group of naturally occurring polyphenolic compounds, considered as active pharmaceutical ingredients.

Poor solubility is a well-recognized property of many drug molecules [1]. Unprotected administration of poorly water-soluble drugs is problematic. Aggregation, precipitation, uncontrolled binding, and direct exposure to a harsh biological environment render this process inefficient. The putative 'solution' of using higher drug concentrations narrows the window between a therapeutic success and unwanted side effects such as locally toxic drug levels. It comes as no surprise that the administration of poorly water-soluble drugs can benefit dramatically from using delivery vehicles. Such vehicles can, in principle, be designed not only to encapsulate a drug and protect it from biological defense mechanisms, but also to release the drug in a controlled manner at the target site and then to be recycled through biodegradation. Different types of delivery vehicles are currently being investigated, including microemulsions [2, 3], gels [4], micelles [5, 6], liposomes [7], polymersomes [8], dendrimers [9], and nanopcrystals [10], or lipid nanoparticles [11]. Notably, most of these are self-assembled structures. Self-assembly is an ubiquitous process in cellular systems, most strikingly perhaps in the cell membrane where a matrix (lipids) contains highly specialized functional units (poorly water-soluble proteins). Functionalization is an advantage that is also increasingly integrated into drug delivery vehicles. As an example Drug Delivery Strategies for Poorly Water-Soluble Drugs, First Edition. Edited by Dennis Douroumis and Alfred Fahr.

The present investigation was enthused by the possibility to develop solid lipid nanoparticles (SLNs) of hydrophilic drug acyclovir (ACV) and evaluate their potential as the carrier for dermal delivery. ACV-loaded SLNs (ACV-SLNs) were prepared by the optimized double emulsion process using Compritol 888 ATO as solid lipid. The prepared SLNs were smooth and spherical in shape with average diameter, polydispersity index, and entrapment efficiency of 262 ± 13 nm, 0.280 ± 0.01, and 40.08 ± 4.39% at 10% (w/w) theoretical drug loading with respect to Compritol 888 ATO content. Differential scanning calorimetry and powder X-ray diffraction pattern revealed that ACV was present in the amorphous state inside the SLNs. In vitro skin permeation studies on human cadaver and Sprague–Dawley rat skin revealed 17.65 and 15.17 times higher accumulation of ACV-SLNs in the dermal tissues in comparison to commercially available ACV cream after 24 h. Mechanism of topical permeation and dermal distribution was studied qualitatively using confocal laser scanning microscopy. While free dye (calcein) failed to penetrate skin barrier, the same encapsulated in SLNs penetrated deeply into the dermal tissue suggesting that pilosebaceous route was followed by SLNs for skin penetration. Histological examination and transdermal epidermal water loss measurement suggested that no major morphological changes occurred on rat skin surface due to the application of SLNs. Overall, it was concluded that ACV-loaded SLNs might be beneficial in improving dermal delivery of antiviral agent(s) for the treatment of topical herpes simplex infection.

Bioactive products from snail slime of " Helix " specie have potential applications in preventing and/or treating several human diseases and in cancer diagnosis. However, the poor pharmacokinetics characteristics of these natural compounds limit their use. Nanotechnology offers promising solutions for the enhanced formulation of these molecules through the synthesis of nanosized drug delivery systems. These vectors are characterized by facilitated transport across the biological barriers, enhanced bioavailability, targeted delivery and the capacity to protect sensitive compounds from biological and environmental degradation. Overall, this review focus on the description of bioactive natural substances derived from snails belonging to the genus helix and their successfully combinations with nanosized vectors.

The aim of this study was to assess the application of Eudragit RL PO and RS PO and their combination for production of ibuprofen pellets by extrusion-spheronization. The pellets were prepared based on full factorial design. Independent variables were % ibuprofen (40, 60, 80), the ratio of Eudragit RS to Eudragit RL (1:0, 1:1, 0:1) and % PVP (1, 3, 5). The evaluated responses were mean dissolution time (MDT), crushing strength and elastic modulus of pellets. Surface characteristics, sphericity and aspect ratio of pellets were also evaluated. Linear regression and response surface modeling was used for analyzing results. It was shown that the amount of water required to prepare a proper wet mass was affected by composition of formulations. The required amount of water decreased with increasing drug load and percent of PVP. It was also shown that formulations containing Eudragit RL need more water. Increasing percent of PVP slightly decreased MDT and elastic modulus but had negligible effect on crushing strength. Increasing the percent of ibuprofen up to 60% decreased MDT but beyond that increased MDT. Increasing the percent of ibuprofen also decreased elastic modulus of pellets. Eudragit RL PO compare with Eudragit RS PO resulted in pellets with high crushing strength; however, Eudragit type did not have a significant effect on elastic modulus.