Showing papers on "Solid lipid nanoparticle published in 2019"

Application of Solid Lipid Nanoparticles to Improve the Efficiency of Anticancer Drugs

Abstract: Drug delivery systems have opened new avenues to improve the therapeutic effects of already-efficient molecules. Particularly, Solid Lipid Nanoparticles (SLNs) have emerged as promising nanocarriers in cancer therapy. SLNs offer remarkable advantages such as low toxicity, high bioavailability of drugs, versatility of incorporation of hydrophilic and lipophilic drugs, and feasibility of large-scale production. Their molecular structure is crucial to obtain high quality SLN preparations and it is determined by the relationship between the composition and preparation method. Additionally, SLNs allow overcoming several physiological barriers that hinder drug delivery to tumors and are also able to escape multidrug resistance mechanisms, characteristic of cancer cells. Focusing on cell delivery, SLNs can improve drug delivery to target cells by different mechanisms, such as passive mechanisms that take advantage of the tumor microenvironment, active mechanisms by surface modification of SLNs, and codelivery mechanisms. SLNs can incorporate many different drugs and have proven to be effective in different types of tumors (i.e., breast, lung, colon, liver, and brain), corroborating their potential. Finally, it has to be taken into account that there are still some challenges to face in the application of SLNs in anticancer treatments but their possibilities seem to be high.

Brain Delivery of Curcumin Using Solid Lipid Nanoparticles and Nanostructured Lipid Carriers: Preparation, Optimization, and Pharmacokinetic Evaluation.

Abstract: Curcumin is a multitherapeutic agent with great therapeutic potential in central nervous system (CNS) diseases. In the current study, curcumin was encapsulated in solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for the purpose of increasing brain accumulation. The preparation processes have been optimized using experimental design and multiobjective optimization methods. Entrapment efficiency of curcumin in SLNs and NLCs was found to be 82% ± 0.49 and 94% ± 0.74, respectively. The pharmacokinetic studies showed that the amount of curcumin available in the brain was significantly higher in curcumin-loaded NLCs (AUC0-t = 505.76 ng/g h) compared to free curcumin (AUC0-t = 0.00 ng/g h) and curcumin-loaded SLNs (AUC0-t = 116.31 ng/g h) (P < 0.005), after intravenous (IV) administration of 4 mg/kg dose of curcumin in rat. The results of differential scanning calorimetry and X-ray diffraction showed that curcumin has been dispersed as amorphous in the nanocarriers. Scanning electron mic...

Natamycin solid lipid nanoparticles - sustained ocular delivery system of higher corneal penetration against deep fungal keratitis: preparation and optimization.

Abstract: Background Fungal keratitis (FK) is a serious pathogenic condition usually associated with significant ocular morbidity. Natamycin (NAT) is the first-line and only medication approved by the Food and Drug Administration for the treatment of FK. However, NAT suffers from poor corneal penetration, which limits its efficacy for treating deep keratitis. Purpose The objective of this work was to prepare NAT solid lipid nanoparticles (NAT-SLNs) to achieve sustained drug release and increased corneal penetration. Methods NAT-SLNs were prepared using the emulsification-ultrasonication technique. Box- Behnken experimental design was applied to optimize the effects of independent processing variables (lipid concentration [X1], surfactant concentration [X2], and sonication frequency [X3]) on particle size (R1), zeta potential (ZP; R2), and drug entrapment efficiency (EE%) (R3) as responses. Drug release profile, ex vivo corneal permeation, antifungal susceptibility, and cytotoxicity of the optimized formula were evaluated. Results The optimized formula had a mean particle size of 42 r.nm (radius in nanometers), ZP of 26 mV, and EE% reached ~85%. NAT-SLNs showed an extended drug release profile of 10 hours, with enhanced corneal permeation in which the apparent permeability coefficient (Papp) and steady-state flux (Jss) reached 11.59×10-2 cm h-1 and 3.94 mol h-1, respectively, in comparison with 7.28×10-2 cm h-1 and 2.48 mol h-1 for the unformulated drug, respectively. Antifungal activity was significantly improved, as indicated by increases in the inhibition zone of 8 and 6 mm against Aspergillus fumigatus ATCC 1022 and a Candida albicans clinical isolate, respectively, and minimum inhibitory concentration values that were decreased 2.5-times against both of these pathogenic strains. NAT-SLNs were found to be non-irritating to corneal tissue. NAT-SLNs had a prolonged drug release rate, that improved corneal penetration, and increased antifungal activity without cytotoxic effects on corneal tissues. Conclusion Thus, NAT-SLNs represent a promising ocular delivery system for treatment of deep corneal keratitis.

pH‐Responsive PEG‐Shedding and Targeting Peptide‐Modified Nanoparticles for Dual‐Delivery of Irinotecan and microRNA to Enhance Tumor‐Specific Therapy

Abstract: Irinotecan is one of the main chemotherapeutic agents for colorectal cancer (CRC). MicroRNA-200 (miR-200) has been reported to inhibit metastasis in cancer cells. Herein, pH-sensitive and peptide-modified liposomes and solid lipid nanoparticles (SLN) are designed for encapsulation of irinotecan and miR-200, respectively. These peptides include one cell-penetrating peptide, one ligand targeted to tumor neovasculature undergoing angiogenesis, and one mitochondria-targeting peptide. The peptide-modified nanoparticles are further coated with a pH-sensitive PEG-lipid derivative with an imine bond. These specially-designed nanoparticles exhibit pH-responsive release, internalization, and intracellular distribution in acidic pH of colon cancer HCT116 cells. These nanoparticles display low toxicity to blood and noncancerous intestinal cells. Delivery of miR-200 by SLN further increases the cytotoxicity of irinotecan-loaded liposomes against CRC cells by triggering apoptosis and suppressing RAS/β-catenin/ZEB/multiple drug resistance (MDR) pathways. Using CRC-bearing mice, the in vivo results further indicate that irinotecan and miR-200 in pH-responsive targeting nanoparticles exhibit positive therapeutic outcomes by inhibiting colorectal tumor growth and reducing systemic toxicity. Overall, successful delivery of miR and chemotherapy by multifunctional nanoparticles may modulate β-catenin/MDR/apoptosis/metastasis signaling pathways and induce programmed cancer cell death. Thus, these pH-responsive targeting nanoparticles may provide a potential regimen for effective treatment of colorectal cancer.

Potential of Lipid Nanoparticles (SLNs and NLCs) in Enhancing Oral Bioavailability of Drugs with Poor Intestinal Permeability

Abstract: Lipid-based drug delivery systems has become a popular choice for oral delivery of lipophilic drugs with dissolution rate limited oral absorption. Lipids are known to enhance oral bioavailability of poorly water-soluble drugs in multiple ways like facilitating dissolution as micellar solution, enhancing the lymphatic uptake and acting as inhibitors of efflux transporters. Lipid nanoparticles are matrix type lipid-based carrier systems which can effectively encapsulate both lipophilic and hydrophilic drugs. Lipid nanoparticles namely solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) are versatile drug delivery system and can be used for multiple routes of delivery like parenteral, topical, ocular, transdermal, and oral. Lipid nanoparticles are particularly attractive vehicles for peroral delivery of drugs with oral bioavailability problems as they are composed of lipid excipients which are cheap, easily available, and non-toxic; manufacturing technique is simple and readily scalable for large-scale production; the formulations provide controlled release of active components and have no stability issue. A large number of drugs have been incorporated into lipid nanoparticles with the objective of overcoming their poor oral bioavailability. This review tries to assess the potential of lipid nanoparticles for enhancing the oral bioavailability of drugs with permeability limited oral absorption such as drugs belonging to class IV of Biopharmaceutic Classification System (BCS) and protein and peptide drugs and also discusses the mechanism behind the bioavailability enhancement and safety issues related to such delivery systems.

Using Supercritical Fluid Technology as a Green Alternative During the Preparation of Drug Delivery Systems.

Abstract: Micro- and nano-carrier formulations have been developed as drug delivery systems for active pharmaceutical ingredients (APIs) that suffer from poor physico-chemical, pharmacokinetic, and pharmacodynamic properties. Encapsulating the APIs in such systems can help improve their stability by protecting them from harsh conditions such as light, oxygen, temperature, pH, enzymes, and others. Consequently, the API's dissolution rate and bioavailability are tremendously improved. Conventional techniques used in the production of these drug carrier formulations have several drawbacks, including thermal and chemical stability of the APIs, excessive use of organic solvents, high residual solvent levels, difficult particle size control and distributions, drug loading-related challenges, and time and energy consumption. This review illustrates how supercritical fluid (SCF) technologies can be superior in controlling the morphology of API particles and in the production of drug carriers due to SCF's non-toxic, inert, economical, and environmentally friendly properties. The SCF's advantages, benefits, and various preparation methods are discussed. Drug carrier formulations discussed in this review include microparticles, nanoparticles, polymeric membranes, aerogels, microporous foams, solid lipid nanoparticles, and liposomes.

Enhancing Curcumin Oral Bioavailability Through Nanoformulations

Abstract: Curcumin is a promising therapeutic agent that exhibits manifold therapeutic activities. However, it is challenging to study curcumin as it exhibits poor aqueous solubility and low permeability and it is a substrate for P-glycoprotein (P-gp). It is readily metabolized in the body, but many active metabolites of curcumin have been identified that could also be exploited for therapy. Strategies for the oral bioenhancement of curcumin to leverage the potential of curcumin as a therapeutic molecule are discussed here in light of these challenges. A brief discussion of conventional bioenhancement strategies using cyclodextrin complexes, solid dispersions, and solid self-emulsifying drug delivery systems is given. However, the major focus of this review is the application of nano-based approaches to the bioenhancement of curcumin. A description of the main advantages of nanosystems is followed by a detailed review of various nanosystems of curcumin, including nanosuspensions and various carrier-based nanosystems. Each nanosystem considered here is first briefly introduced, and then studies of the nanosystem containing curcumin are discussed. Lipid-based systems including liposomes and solid lipid nanoparticles, microemulsions, self-microemulsifying drug-delivery systems, nanoemulsions, and polymeric nanoparticles—which are widely explored—are dealt with in detail. Other miscellaneous systems discussed include inorganic nanoparticles, micelles, solid nanodispersions, phytosomes, and dendrimers. The possibility of using intact nanoparticles to achieve the targeted oral delivery of curcumin and thus harness the benefits of this wonder nutraceutical is an exciting prospect.

Solid Lipid Nanoparticles: A Promising Nanomaterial in Drug Delivery.

Abstract: The solid lipid nanoparticles (SLNs) usually consists of active drug molecules along with solid lipids, surfactants, and/or co-surfactants. They possess some potential features such as nano-size, surface with a free functional group to attach ligands, and as well they prove safe homing for both lipophilic as well as hydrophilic molecules. As far as synthesis is concerned, SLNs can be prepared by employing various techniques viz., homogenization techniques (e.g., high-pressure, high-speed, cold, or hot homogenization), spray drying technique, ultrasonication, solvent emulsification, double emulsion technique, etc. Apart from this, they are characterized by different methods for determining various parameters like particle-size, polydispersity-index, surface morphology, DSC, XRD, etc. SLNs show good stability as well as the ability for surface tailoring with the specific ligand, which makes them a suitable candidate in the therapy of numerous illnesses, especially in the targeting of the cancers. In spite of this, SLNs have witnessed their application via various routes e.g., oral, parenteral, topical, pulmonary, rectal routes, etc. Eventually, SLNs have also shown great potential for delivery of gene/DNA, vaccines, as well as in cosmeceuticals. Hence, SLNs have emerged as a promising nanomaterial for efficient delivery of various Active Pharmaceutical Ingredients (APIs).

Lipid-Based Nanoparticles for Drug-Delivery Systems

Abstract: The discovery of new drug molecules depends on a number of steps, which limits the development of feasible new drugs for the treatment of disease without any side effects. However, most drugs fail in the clinical stage even though they showed good biological activity in in vitro and in vivo studies. This is may be due to the lack of a physiological environment during the in vitro and in vivo studies. Hence, most research and development is focusing on alternative ways to develop drug molecules that are suitable for treatment without side effects through the formulation of suitable drug-delivery systems. There are a number of processes and techniques developed for drug delivery, and one such technique is lipid-based nanoparticles as carriers for drug delivery. The major advantages of lipids are high biocompatibility and biodegradability. In this chapter, we discuss lipid-based nanocarrier systems such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, and self-emulsification drug-delivery systems. The focus of this chapter is a detailed discussion of the various lipid-based nanocarrier systems, formulations, and characterization techniques. We also briefly discuss the different routes of administration of lipid-based nanoparticles and their application in drug-delivery systems for various kinds of treatment.

Use of Lipid Nanocarriers to Improve Oral Delivery of Vitamins

Abstract: The chemical environment and enzymes in the gastrointestinal (GI) membrane limit the oral absorption of some vitamins. The GI epithelium also contributes to the poor permeability of numerous antioxidant agents. Thus, lipophilic vitamins do not readily dissolve in the GI tract, and therefore they have low bioavailability. Nanomedicine has the potential to improve the delivery efficiency of oral vitamins. In particular, the use of lipid nanocarriers for certain vitamins that are administered orally can provide improved solubility, chemical stability, epithelium permeability and bioavailability, half-life, nidus targeting, and fewer adverse effects. These lipid nanocarriers include self-emulsifying drug delivery systems (SEDDSs), nanoemulsions, microemulsions, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs). The use of nontoxic excipients and sophisticated material engineering of lipid nanosystems allows for control of the physicochemical properties of the nanoparticles and improved GI permeation via mucosal or lymphatic transport. In this review, we highlight recent progress in the development of lipid nanocarriers for vitamin delivery. In addition, the same lipid nanocarriers used for vitamins may also be effective as carriers of vitamin derivatives, and therefore enhance their oral bioavailability. One example is the incorporation of d-α-tocopheryl polyethylene glycol succinate (TPGS) as the emulsifier in lipid nanocarriers to increase the solubility and inhibit P-glycoprotein (P-gp) efflux. We also survey the concepts and discuss the mechanisms of nanomedical techniques that are used to develop vitamin-loaded nanocarriers.

Preparation and evaluation of tacrolimus-loaded thermosensitive solid lipid nanoparticles for improved dermal distribution.

Abstract: Background: Tacrolimus (TCR), also known as FK-506, is a biopharmaceutics classification system (BCS) class II drug that is insoluble in water because of its high log P values. After dermal application, TCR remains in the stratum corneum and passes through the skin layers with difficulty. Purpose: The objectives of this study were to develop and evaluate solid lipid nanoparticles (SLNs) with thermosensitive properties to improve penetration and retention. Methods: We prepared TCR-loaded thermosensitive solid lipid nanoparticles (TCR-SLNs) with different types of surfactants on the shell of the particle, which conferred the advantages of enhancing skin permeation and distribution. We also characterized them from a physic point of view and performed in vitro and in vivo evaluations. Results: The TCR contained in the prepared TCR-SLN was in an amorphous state and entrapped in the particles with a high loading efficiency. The assessment of ex vivo skin penetration using excised rat dorsal skin showed that the TCR-SLNs penetrated to a deeper layer than the reference product (0.1% Protopic®). In addition, the in vivo skin penetration test demonstrated that TCR-SLNs delivered more drug into deeper skin layers than the reference product. FT-IR images also confirmed drug distribution of TCR-SLNs into deeper layers of the skin. Conclusion: These results revealed the potential application of thermosensitive SLNs for the delivery of difficult-to-permeate, poorly water-soluble drugs into deep skin layers.

Lipid-Based Nanoparticles for Drug Delivery Systems

Abstract: Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have opened new horizons in the pharmaceutical industry since they play a fundamental role in the field of drug delivery. Their success is mainly due to their interesting physicochemical behaviors, such as high bioavailability, capability of administration through different routes, large-scale production, inherent ability to cross the blood brain barrier, and the ability to deliver macromolecules like proteins, oligonucleotides, and DNA. The purpose of this review is to provide a brief description of the advantages, disadvantages, and production techniques, as well as their potential in the drug delivery area so far.

Nanocapsules for Drug Delivery: An Updated Review of the Last Decade.

Abstract: Background For the past few decades, there has been considerable research interest in drug delivery strategies using nanoparticulate systems as carriers for a wide range of active pharmaceutical ingredients. Objective It is known that nanoparticulate drug delivery systems comprise a wide variety of dosage forms including nanospheres, micelles, solid lipid nanoparticles, nanoliposomes, dendrimers, magnetic nanoparticles, and nanocapsules. Methods This review describes nanocapsule preparation techniques and their applications for the treatment of several diseases using patents and examples from the literature. Results Nanocapsules are vesicular systems consisting of an inner liquid core (aqueous/oily) surrounded by a polymeric wall that has immense potential as drug carriers because of the many advantages like improving poor aqueous solubility, stabilizing drugs by protecting the molecule from the environment, providing the desired pharmacokinetic profile, allowing controlled release, as well as facilitating oral administration. Conclusion The present study discusses and summarizes patents related to preparation methods of and recent studies from the last 10 years on nanocapsules as drug delivery systems.

Short Term Stability Testing of Efavirenz-Loaded Solid Lipid Nanoparticle (SLN) and Nanostructured Lipid Carrier (NLC) Dispersions

Abstract: The short term stability of efavirenz-loaded solid lipid nanoparticle and nanostructured lipid carrier dispersions was investigated. Hot High Pressure Homogenization with the capability for scale up production was successfully used to manufacture the nanocarriers without the use of toxic organic solvents for the first time. Glyceryl monostearate and Transcutol® HP were used as the solid and liquid lipids. Tween® 80 was used to stabilize the lipid nanocarriers. A Box-Behnken Design was used to identify the optimum operating and production conditions viz., 1100 bar for 3 cycles for the solid lipid nanoparticles and 1500 bar for 5 cycles for nanostructured lipid carriers. The optimized nanocarriers were predicted to exhibit 10% efavirenz loading with 3% and 4% Tween® 80 for solid lipid nanoparticles and nanostructured lipid carriers, respectively. Characterization of the optimized solid lipid nanoparticle and nanostructured lipid carrier formulations in relation to shape, surface morphology, polymorphism, crystallinity and compatibility revealed stable formulations with particle sizes in the nanometer range had been produced. The nanocarriers had excellent efavirenz loading with the encapsulation efficiency >90%. The optimized nanocarriers exhibited biphasic in vitro release patterns with an initial burst release during the initial 0-3 h followed by sustained release over a 24 h period The colloidal systems showed excellent stability in terms of Zeta potential, particle size, polydispersity index and encapsulation efficiency when stored for 8 weeks at 25 °C/60% RH in comparison to when stored at 40 °C/75% RH. The formulations manufactured using the optimized conditions and composition proved to be physically stable as aqueous dispersions.

Role of solid lipid nanoparticles as photoprotective agents in cosmetics.

Abstract: Background Novel drug delivery systems have gained popularity since last two decades because of its advantages over conventional dosage forms. Effect of UV radiation on skin can cause either acute or chronic damage to our skin. Solid lipid nanoparticles (SLNs) were developed as novel carrier over the conventional carrier systems like liposomes and emulsions. The SLNs were selected as a carrier for the formulation because of its ability to protect the labile drug particles, the ability to make the drug release in a controlled manner, and occlusive property of the SLNs. Objective The current review is an attempt to focus on the characteristics of solid lipid nanoparticles, methods for the preparations, and their cosmetic applications along with some future perspectives of the nanodrug delivery systems. Methods A review of the current literature of solid lipid nanoparticles (SLNs) as novel carrier showed better photoprotection in sunscreens. Results and conclusions The disadvantages of conventional sunscreens can be overcome by incorporation of solid lipid nanoparticles. On comparing the lipid nanobased systems with traditional cosmetic products, the occlusion can be achieved without the use of paraffin and other greasy oils. The film formed by lipid nanoparticles will be smooth as compared to the inflexible films formed by the paraffin. Newer approaches may lead to even better results. They also possess excellent UV-blocking activity and showed better photoprotection.

Development, Optimization, and In Vitro/In Vivo Characterization of Enhanced Lipid Nanoparticles for Ocular Delivery of Ofloxacin: the Influence of Pegylation and Chitosan Coating

Abstract: This study aims to investigate whether modification of solid lipid nanoparticles (SLNs) with chitosan (CTS) and polyethylene glycol (PEG) coatings enhances corneal retention time and transcorneal bioavailability. Ofloxacin (OFLOX) was selected as the model drug because of its potential benefits for the treatment of local eye infections. The OFLOX-CTS-PEG-SLN was prepared by a modified emulsion/solvent evaporation technique. A central composite design was implemented to investigate the influence of total lipid/drug ratio, surfactant concentration, PEG stearate concentration in the lipid mixture, and CTS concentration on size, entrapment, transcorneal permeation, and adhesion to the corneal mucosal membrane. The optimized OFLOX-CTS-PEG-SLN was characterized for OFLOX cumulative percentage released in simulated tear fluid and permeated across the excised bovine corneal membrane. Moreover, nanoparticle morphology, eye irritation via histopathological analysis, and OFLOX concentration in the ocular fluids and tissues were determined. A total lipid/drug ratio of 19:1, Tween 80 of 2%, PEG stearate concentration in the lipid mixture (% w/w) of 2.6%, and CTS concentration (% w/v) of 0.23% produced 132.9 nm particles entrapping 74.8% of the total drug added. The particles detached from the corneal membrane at a force of 3700 dyne/cm2. The %OFLOX released from the optimized nanoparticles was 63.3, and 66% of the drug permeated after 24 h. Compared to Oflox® drops, the optimized OFLOX-CTS-PEG-SLN exhibited similar tolerability but two- to threefold higher concentrations in the eyes of rabbits. Coating of SLN with chitosan and PEG augments the ocular bioavailability of OFLOX by increasing transcorneal permeation and enhancing mucoadhesion strength.

Development and Optimization of Alpha-Pinene-Loaded Solid Lipid Nanoparticles (SLN) Using Experimental Factorial Design and Dispersion Analysis

Abstract: The encapsulation of bicyclic monoterpene α-pinene into solid lipid nanoparticles (SLN) is reported using experimental factorial design, followed by high-end dispersion analyzer LUMiSizer®. This equipment allows the characterization of the α-pinene-loaded SLN instability phenomena (e.g., sedimentation, flotation or coagulation), as well as the determination of the velocity distribution in the centrifugal field and the particle size distribution. In this work, SLN were produced by hot high-pressure homogenization technique. The influence of the independent variables, surfactant and lipid ratio on the physicochemical properties of SLN, such as mean particle size (Z-Ave), polydispersity index (PDI) and zeta potential (ZP), was estimated using a 22-factorial design. The Z-Ave and PDI were analyzed by dynamic light scattering, while ZP measurements were recorded by electrophoretic light scattering. Based on the obtained results, the optimal SLN dispersion was composed of 1 wt.% of α-pinene, 4 wt.% of solid lipid (Imwitor® 900 K) and 2.5 wt.% of surfactant (Poloxamer 188), depicting 136.7 nm of Z-Ave, 0.170 of PDI and 0 mV of ZP. Furthermore, LUMISizer® has been successfully used in the stability analysis of α-pinene-loaded SLN.

Lipid-based carriers for the delivery of local anesthetics.

Abstract: Introduction: There is a clinical need for pharmaceutical dosage forms devised to prolong the acting time of local anesthetic (LA) agents or to reduce their toxicity. Encapsulation of LA in drug de...