Showing papers on "Solid lipid nanoparticle published in 2021"

Lipid Nanoparticles-From Liposomes to mRNA Vaccine Delivery, a Landscape of Research Diversity and Advancement.

Abstract: Lipid nanoparticles (LNPs) have emerged across the pharmaceutical industry as promising vehicles to deliver a variety of therapeutics. Currently in the spotlight as vital components of the COVID-19 mRNA vaccines, LNPs play a key role in effectively protecting and transporting mRNA to cells. Liposomes, an early version of LNPs, are a versatile nanomedicine delivery platform. A number of liposomal drugs have been approved and applied to medical practice. Subsequent generations of lipid nanocarriers, such as solid lipid nanoparticles, nanostructured lipid carriers, and cationic lipid-nucleic acid complexes, exhibit more complex architectures and enhanced physical stabilities. With their ability to encapsulate and deliver therapeutics to specific locations within the body and to release their contents at a desired time, LNPs provide a valuable platform for treatment of a variety of diseases. Here, we present a landscape of LNP-related scientific publications, including patents and journal articles, based on analysis of the CAS Content Collection, the largest human-curated collection of published scientific knowledge. Rising trends are identified, such as nanostructured lipid carriers and solid lipid nanoparticles becoming the preferred platforms for numerous formulations. Recent advancements in LNP formulations as drug delivery platforms, such as antitumor and nucleic acid therapeutics and vaccine delivery systems, are discussed. Challenges and growth opportunities are also evaluated in other areas, such as medical imaging, cosmetics, nutrition, and agrochemicals. This report is intended to serve as a useful resource for those interested in LNP nanotechnologies, their applications, and the global research effort for their development.

Lipid nanoparticles as carriers for bioactive delivery

Abstract: Nanotechnology has made a great impact on the pharmaceutical, biotechnology, food, and cosmetics industries. More than 40% of the approved drugs are lipophilic and have poor solubility. This is the major rate-limiting step that influences the release profile and bioavailability of drugs. Several approaches have been reported to administer lipophilic drugs with improved solubility and bioavailability. Nanotechnology plays a crucial role in the targeted delivery of poorly soluble drugs. Nanotechnology-based drug delivery systems can be classified as solid lipid nanoparticulate drug delivery systems, emulsion-based nanodrug delivery systems, vesicular drug delivery systems, etc. Nanotechnology presents a new frontier in research and development to conquer the limitations coupled with the conventional drug delivery systems through the formation of specific functionalized particles. This review presents a bird's eye view on various aspects of lipid nanoparticles as carriers of bioactive molecules that is, synthesis, characterization, advantage, disadvantage, toxicity, and application in the medical field. Update on recent development in terms of patents and clinical trials of solid lipid nanoparticles (SLNs) and nanostructure lipid carriers (NLCs) have also been discussed in this article.

Food-Grade Colloidal Systems for the Delivery of Essential Oils

Abstract: This review presents a critical analysis of food-grade delivery systems, which are suitable for the delivery of essential oils (EOs) for food applications. In particular, the main colloidal...

Formulation development of linagliptin solid lipid nanoparticles for oral bioavailability enhancement: role of P-gp inhibition

Abstract: Linagliptin (LGP), a novel anti-diabetic drug, is a DPP-4 inhibitor used in the treatment of type II diabetes. One of the major disadvantages of LGP is its low oral bioavailability (29.5%) due to first-pass metabolism and P-gp efflux. In an attempt to increase the oral bioavailability, LGP solid lipid nanoparticles (LGP-SLNs) were developed with poloxamer 188 and Tween 80 as P-gp inhibitors. LGP-SLNs were formulated using palmitic acid, poloxamer 188 and Tween 80 as lipid, surfactant and co-surfactant, respectively, by hot homogenization ultrasonication method and optimized using 32 full factorial designs. Particle size, entrapment efficiency (%EE) and drug release at 24 h were evaluated as responses. An optimized batch of LGP-SLNs (L12) was evaluated for intestinal transport of LGP by conducting in situ single-pass intestinal perfusion (SPIP), everted gut sac and Caco-2 permeability study. The pharmacokinetic and pharmacodynamic evaluation of L12 was carried out in albino Wistar rats. The mean particle size, polydispersity index, zeta potential and %EE of L12 were found to be 225.96 ± 2.8 nm, 0.180 ± 0.034, − 5.4 ± 1.07 mV and 73.8 ± 1.73%, respectively. %CDR of 80.96 ± 3.13% was observed in 24 h. The permeability values of LGP-SLNs in the absorptive direction were 1.82-, 1.76- and 1.74-folds higher than LGP-solution (LGP-SOL) in SPIP, everted gut sac and Caco-2 permeability studies, respectively. LGP-SLNs exhibited relative bioavailability of 300% and better reduction in glucose levels in comparison with LGP-SOL in rats. The enhanced oral bioavailability exhibited by LGP-SLNs bioavailability may be due to P-gp efflux inhibition and lymphatic targeting. Improved bioabsorption can cause reduction in dose, dose-related side effects and frequency of administration. Thus, LGP-SLNs can be considered promising carriers for oral delivery but clinical studies are required to confirm the proof of concept. Graphical abstract

Clarithromycin Solid Lipid Nanoparticles for Topical Ocular Therapy: Optimization, Evaluation and In Vivo Studies.

Abstract: Solid lipid nanoparticles (SLNs) are being extensively exploited as topical ocular carrier systems to enhance the bioavailability of drugs. This study investigated the prospects of drug-loaded SLNs to increase the ocular permeation and improve the therapeutic potential of clarithromycin in topical ocular therapy. SLNs were formulated by high-speed stirring and the ultra-sonication method. Solubility studies were carried out to select stearic acid as lipid former, Tween 80 as surfactant, and Transcutol P as cosurfactant. Clarithromycin-loaded SLN were optimized by fractional factorial screening and 32 full factorial designs. Optimized SLNs (CL10) were evaluated for stability, morphology, permeation, irritation, and ocular pharmacokinetics in rabbits. Fractional factorial screening design signifies that the sonication time and amount of lipid affect the SLN formulation. A 32 full factorial design established that both factors had significant influences on particle size, percent entrapment efficiency, and percent drug loading of SLNs. The release profile of SLNs (CL9) showed ~80% drug release in 8 h and followed Weibull model kinetics. Optimized SLNs (CL10) showed significantly higher permeation (30.45 μg/cm2/h; p < 0.0001) as compared to control (solution). CL10 showed spherical shape and good stability and was found non-irritant for ocular administration. Pharmacokinetics data demonstrated significant improvement of clarithromycin bioavailability (p < 0.0001) from CL10, as evidenced by a 150% increase in Cmax (~1066 ng/mL) and a 2.8-fold improvement in AUC (5736 ng h/mL) (p < 0.0001) as compared to control solution (Cmax; 655 ng/mL and AUC; 2067 ng h/mL). In summary, the data observed here demonstrate the potential of developed SLNs to improve the ocular permeation and enhance the therapeutic potential of clarithromycin, and hence could be a viable drug delivery approach to treat endophthalmitis.

Design, Preparation, and Characterization of Effective Dermal and Transdermal Lipid Nanoparticles: A Review

Abstract: Limited permeability through the stratum corneum (SC) is a major obstacle for numerous skin care products. One promising approach is to use lipid nanoparticles as they not only facilitate penetration across skin but also avoid the drawbacks of conventional skin formulations. This review focuses on solid lipid nanoparticles (SLNs), nanostructured lipid nanocarriers (NLCs), and nanoemulsions (NEs) developed for topical and transdermal delivery of active compounds. A special emphasis in this review is placed on composition, preparation, modifications, structure and characterization, mechanism of penetration, and recent application of these nanoparticles. The presented data demonstrate the potential of these nanoparticles for dermal and transdermal delivery.

Lipid-Based Nanosystems as a Tool to Overcome Skin Barrier.

Abstract: Skin may be affected by many disorders that can be treated by topical applications of drugs on the action site. With the advent of nanotechnologies, new efficient delivery systems have been developed. Particularly, lipid-based nanosystems such as liposomes, ethosomes, transferosomes, solid lipid nanoparticles, nanostructured lipid carriers, cubosomes, and monoolein aqueous dispersions have been proposed for cutaneous application, reaching in some cases the market or clinical trials. This review aims to provide an overview of the different lipid-based nanosystems, focusing on their use for topical application. Particularly, biocompatible nanosystems able to dissolve lipophilic compounds and to control the release of carried drug, possibly reducing side effects, are described. Notably, the rationale to topically administer antioxidant molecules by lipid nanocarriers is described. Indeed, the structural similarity between the nanosystem lipid matrix and the skin lipids allows the achievement of a transdermal effect. Surely, more research is required to better understand the mechanism of interaction between lipid-based nanosystems and skin. However, this attempt to summarize and highlight the possibilities offered by lipid-based nanosystems could help the scientific community to take advantage of the benefits derived from this kind of nanosystem.

Evaluation and Comparison of Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs) as Vectors to Develop Hydrochlorothiazide Effective and Safe Pediatric Oral Liquid Formulations.

Abstract: The aim of this study was the optimization of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in terms of physicochemical and biopharmaceutical properties, to develop effective and stable aqueous liquid formulations of hydrochlorothiazide, suitable for paediatric therapy, overcoming its low-solubility and poor-stability problems. Based on solubility studies, Precirol® ATO5 and Transcutol® HP were used as solid and liquid lipids, respectively. The effect of different surfactants, also in different combinations and at different amounts, on particle size, homogeneity and surface-charge of nanoparticles was carefully investigated. The best formulations were selected for drug loading, and evaluated also for entrapment efficiency and release behaviour. For both SLN and NLC series, the use of Gelucire® 44/14 as surfactant rather than PluronicF68 or Tween® 80 yielded a marked particle size reduction (95–75 nm compared to around 600–400 nm), and an improvement in entrapment efficiency and drug release rate. NLC showed a better performance than SLN, reaching about 90% entrapped drug (vs. 80%) and more than 90% drug released after 300 min (vs. about 65%). All selected formulations showed good physical stability during 6-month storage at 4 °C, but a higher loss of encapsulated drug was found for SLNs (15%) than for NLCs (<5%). Moreover, all selected formulations revealed the absence of any cytotoxic effect, as assessed by a cell-viability test on Caco-2 cells and are able to pass the intestinal epithelium as suggested by Caco-2 uptake experiments.

Exploiting solid lipid nanoparticles and nanostructured lipid carriers for drug delivery against cutaneous fungal infections

Abstract: Several types of cutaneous fungal infections can affect the population worldwide, such as dermatophytosis, cutaneous candidiasis, onychomycosis, and sporotrichosis. However, oral treatments have pronounced adverse effects, making the topical route an alternative to avoid this disadvantage. On the other hand, currently available pharmaceutical forms designed for topical application, such as gels and creams, do not demonstrate effective retention of biomolecules in the upper layers of the skin. An interesting approach to optimise biomolecules' activity in the skin is the use of nanosystems for drug delivery, especially solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), which in the past decade has shown advantages like increased adhesiveness, great occlusive properties and higher biomolecule deposition in stratum corneum when designed for topical application. Considering the demand for more effective therapeutic alternatives and the promising characteristics of SLN and NLC for topical application, the present study sought to gather studies that investigated the potential of using SLN and NLC for the treatment of cutaneous fungal infections. Studies demonstrated that these nanosystems showed optimisation, mostly, of the effectiveness of biomolecules besides other biopharmaceutical properties, in addition to offering potential occlusion and hydration of the applied region.

Pharmaceutical Formulations with P-Glycoprotein Inhibitory Effect as Promising Approaches for Enhancing Oral Drug Absorption and Bioavailability.

Abstract: P-glycoprotein (P-gp) is crucial in the active transport of various substrates with diverse structures out of cells, resulting in poor intestinal permeation and limited bioavailability following oral administration. P-gp inhibitors, including small molecule drugs, natural constituents, and pharmaceutically inert excipients, have been exploited to overcome P-gp efflux and enhance the oral absorption and bioavailability of many P-gp substrates. The co-administration of small molecule P-gp inhibitors with P-gp substrates can result in drug–drug interactions and increased side effects due to the pharmacological activity of these molecules. On the other hand, pharmaceutically inert excipients, including polymers, surfactants, and lipid-based excipients, are safe, pharmaceutically acceptable, and are not absorbed from the gut. Notably, they can be incorporated in pharmaceutical formulations to enhance drug solubility, absorption, and bioavailability due to the formulation itself and the P-gp inhibitory effects of the excipients. Different formulations with inherent P-gp inhibitory activity have been developed. These include micelles, emulsions, liposomes, solid lipid nanoparticles, polymeric nanoparticles, microspheres, dendrimers, and solid dispersions. They can bypass P-gp by different mechanisms related to their properties. In this review, we briefly introduce P-gp and P-gp inhibitors, and we extensively summarize the current development of oral drug delivery systems that can bypass and inhibit P-gp to improve the oral absorption and bioavailability of P-gp substrates. Since many drugs are limited by P-gp-mediated efflux, this review is helpful for designing suitable formulations of P-gp substrates to enhance their oral absorption and bioavailability.

Development, Characterization, and Evaluation of SLN-Loaded Thermoresponsive Hydrogel System of Topotecan as Biological Macromolecule for Colorectal Delivery.

Abstract: Background. Chemotherapeutic drugs cause severe toxicities if administered unprotected, without proper targeting, and controlled release. In this study, we developed topotecan- (TPT-) loaded solid lipid nanoparticles (SLNs) for their chemotherapeutic effect against colorectal cancer. The TPT-SLNs were further incorporated into a thermoresponsive hydrogel system (TRHS) (TPT-SLNs-TRHS) to ensure control release and reduce toxicity of the drug. Microemulsion technique and cold method were, respectively, used to develop TPT-SLNs and TPT-SLNs-TRHS. Particle size, polydispersive index (PDI), and incorporation efficiency (IE) of the TPT-SLNs were determined. Similarly, gelation time, gel strength, and bioadhesive force studies of the TPT-SLNs-TRHS were performed. Additionally, in vitro release and pharmacokinetic and antitumour evaluations of the formulation were done. Results. TPT-SLNs have uniformly distributed particles with mean size in nanorange (174 nm) and IE of ~90%. TPT-SLNs-TRHS demonstrated suitable gelation properties upon administration into the rat’s rectum. Moreover, drug release was exhibited in a control manner over an extended period of time for the incorporated TPT. Pharmacokinetic studies showed enhanced bioavailability of the TPT with improved plasma concentration and AUC. Further, it showed significantly enhanced antitumour effect in tumour-bearing mice as compared to the test formulations. Conclusion. It can be concluded that SLNs incorporated in TRHS could be a potential source of the antitumour drug delivery with better control of the drug release and no toxicity.

Lipid-Based Nanocarriers for Ophthalmic Administration: Towards Experimental Design Implementation.

Abstract: Nanotherapeutics based on biocompatible lipid matrices allow for enhanced solubility of poorly soluble compounds in the treatment of ophthalmic diseases, overcoming the anatomical and physiological barriers present in the eye, which, despite the ease of access, remains strongly protected Micro-/nanoemulsions, solid lipid nanoparticles (SLN) or nanostructured lipid carriers (NLC) combine liquid and/or solid lipids with surfactants, improving drug stability and ocular bioavailability Current research and development approaches based on try-and-error methodologies are unable to easily fine-tune nanoparticle populations in order to overcome the numerous constraints of ocular administration routes, which is believed to hamper easy approval from regulatory agencies for these systems The predictable quality and specifications of the product can be achieved through quality-by-design (QbD) implementation in both research and industrial environments, in contrast to the current quality-by-testing (QbT) framework Mathematical modelling of the expected final nanoparticle characteristics by variation of operator-controllable variables of the process can be achieved through adequate statistical design-of-experiments (DoE) application This multivariate approach allows for optimisation of drug delivery platforms, reducing research costs and time, while maximising the understanding of the production process This review aims to highlight the latest efforts in implementing the design of experiments to produce optimised lipid-based nanocarriers intended for ophthalmic administration A useful background and an overview of the different possible approaches are presented, serving as a starting point to introduce the design of experiments in current nanoparticle research

Anacardic acid encapsulated solid lipid nanoparticles for Staphylococcus aureus biofilm therapy: chitosan and DNase coating improves antimicrobial activity

Abstract: Biofilm mediated bacterial infections are the key factors in the progression of infectious diseases due to the evolution of antimicrobial resistance. Traditional therapy involving antibiotics is not adequate enough for treatment of such infections due to the increased resistance triggered by biofilm. To overcome this challenge, we developed anacardic acid (Ana) loaded solid lipid nanoparticles (SLNs), further coated with chitosan and DNase (Ana-SLNs-CH-DNase). The DNase coating was hypothesized to degrade the e-DNA, while chitosan was coated to yield positively charged SLNs with additional adhesion to biofilms. The SLNs were developed using homogenization method and further evaluated for particle size, polydispersity index, zeta potential, and entrapment efficiency. Drug excipient compatibility was confirmed by using FT-IR study, while encapsulation of Ana in SLNs was confirmed by X-ray diffraction study. The SLNs demonstrated sustained release for up to 24 h and excellent stability at room temperature for up to 3 months. The developed SLNs were found non-toxic against human immortalized keratinocyte (HaCaT) cells while demonstrated remarkably higher antimicrobial efficacy against Staphylococcus aureus. Excellent effect of the developed SLNs on minimum biofilm inhibition concentration and minimum biofilm eradication concentration further confirmed the superiority of the developed formulation strategy. A significant (p < 0.05) reduction in biofilm thickness and biomass, as confirmed by confocal laser scanning microscopy, was observed in the case of developed SLNs in comparison with control. Cumulatively, the results suggest the enhanced efficacy of the developed formulation strategy to overcome the biofilm-mediated antimicrobial resistance. Graphical abstract.

In Vitro Studies on Nasal Formulations of Nanostructured Lipid Carriers (NLC) and Solid Lipid Nanoparticles (SLN).

Abstract: The nasal route has been used for many years for the local treatment of nasal diseases. More recently, this route has been gaining momentum, due to the possibility of targeting the central nervous system (CNS) from the nasal cavity, avoiding the blood−brain barrier (BBB). In this area, the use of lipid nanoparticles, such as nanostructured lipid carriers (NLC) and solid lipid nanoparticles (SLN), in nasal formulations has shown promising outcomes on a wide array of indications such as brain diseases, including epilepsy, multiple sclerosis, Alzheimer’s disease, Parkinson’s disease and gliomas. Herein, the state of the art of the most recent literature available on in vitro studies with nasal formulations of lipid nanoparticles is discussed. Specific in vitro cell culture models are needed to assess the cytotoxicity of nasal formulations and to explore the underlying mechanism(s) of drug transport and absorption across the nasal mucosa. In addition, different studies with 3D nasal casts are reported, showing their ability to predict the drug deposition in the nasal cavity and evaluating the factors that interfere in this process, such as nasal cavity area, type of administration device and angle of application, inspiratory flow, presence of mucoadhesive agents, among others. Notwithstanding, they do not preclude the use of confirmatory in vivo studies, a significant impact on the 3R (replacement, reduction and refinement) principle within the scope of animal experiments is expected. The use of 3D nasal casts to test nasal formulations of lipid nanoparticles is still totally unexplored, to the authors best knowledge, thus constituting a wide open field of research.

Incorporation of Antibiotics into Solid Lipid Nanoparticles: A Promising Approach to Reduce Antibiotic Resistance Emergence.

Abstract: Antimicrobial resistance is one of the biggest threats to global health as current antibiotics are becoming useless against resistant infectious pathogens. Consequently, new antimicrobial strategies are urgently required. Drug delivery systems represent a potential solution to improve current antibiotic properties and reverse resistance mechanisms. Among different drug delivery systems, solid lipid nanoparticles represent a highly interesting option as they offer many advantages for nontoxic targeted drug delivery. Several publications have demonstrated the capacity of SLNs to significantly improve antibiotic characteristics increasing treatment efficiency. In this review article, antibiotic-loaded solid lipid nanoparticle-related works are analyzed to summarize all information associated with applying these new formulations to tackle the antibiotic resistance problem. The main antimicrobial resistance mechanisms and relevant solid lipid nanoparticle characteristics are presented to later discuss the potential of these nanoparticles to improve current antibiotic treatment characteristics and overcome antimicrobial resistance mechanisms. Moreover, solid lipid nanoparticles also offer new possibilities for other antimicrobial agents that cannot be administrated as free drugs. The advantages and disadvantages of these new formulations are also discussed in this review. Finally, given the progress of the studies carried out to date, future directions are discussed.