Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have emerged as potential drug delivery systems for various applications that are produced from physiological, biodegradable, and biocompatible lipids. The methods used to produce SLNs and NLCs have been well investigated and reviewed, but solvent injection method provides an alternative means of preparing these drug carriers. The advantages of solvent injection method include a fast production process, easiness of handling, and applicability in many laboratories without requirement of complicated instruments. The effects of formulations and process parameters of this method on the characteristics of the produced SLNs and NLCs have been investigated in several studies. This review describes the methods currently used to prepare SLNs and NLCs with focus on solvent injection method. We summarize recent development in SLNs and NLCs production using this technique. In addition, the effects of solvent injection process parameters on SLNs and NLCs characteristics are discussed.

https://www.mdpi.com/1420-3049/25/20/4781/pdf

Preparation of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Drug Delivery and the Effects of Preparation Parameters of Solvent Injection Method

Neuropsychiatric diseases are one of the main causes of disability, affecting millions of people. Various drugs are used for its treatment, although no effective therapy has been found yet. The blood brain barrier (BBB) significantly complicates drugs delivery to the target cells in the brain tissues. One of the problem-solving methods is the usage of nanocontainer systems. In this review we summarized the data about nanoparticles drug delivery systems and their application for the treatment of neuropsychiatric disorders. Firstly, we described and characterized types of nanocarriers: inorganic nanoparticles, polymeric and lipid nanocarriers, their advantages and disadvantages. We discussed ways to interact with nerve tissue and methods of BBB penetration. We provided a summary of nanotechnology-based pharmacotherapy of schizophrenia, bipolar disorder, depression, anxiety disorder and Alzheimer’s disease, where development of nanocontainer drugs derives the most active. We described various experimental drugs for the treatment of Alzheimer’s disease that include vector nanocontainers targeted on β-amyloid or tau-protein. Integrally, nanoparticles can substantially improve the drug delivery as its implication can increase BBB permeability, the pharmacodynamics and bioavailability of applied drugs. Thus, nanotechnology is anticipated to overcome the limitations of existing pharmacotherapy of psychiatric disorders and to effectively combine various treatment modalities in that direction.

https://www.mdpi.com/1420-3049/25/22/5294/pdf

Nano Carrier Drug Delivery Systems for the Treatment of Neuropsychiatric Disorders: Advantages and Limitations.

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.

https://www.mdpi.com/1999-4923/13/7/1103/pdf

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

Ischemic heart disease (IHD) is the leading cause of disability and mortality worldwide. Reactive oxygen species (ROS) have been shown to play key roles in the progression of diabetes, hypertension, and hypercholesterolemia, which are independent risk factors that lead to atherosclerosis and the development of IHD. Engineered biomaterial‐based nanomedicines are under extensive investigation and exploration, serving as smart and multifunctional nanocarriers for synergistic therapeutic effect. Capitalizing on cell/molecule‐targeting drug delivery, nanomedicines present enhanced specificity and safety with favorable pharmacokinetics and pharmacodynamics. Herein, the roles of ROS in both IHD and its risk factors are discussed, highlighting cardiovascular medications that have antioxidant properties, and summarizing the advantages, properties, and recent achievements of nanomedicines that have ROS scavenging capacity for the treatment of diabetes, hypertension, hypercholesterolemia, atherosclerosis, ischemia/reperfusion, and myocardial infarction. Finally, the current challenges of nanomedicines for ROS‐scavenging treatment of IHD and possible future directions are discussed from a clinical perspective.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/adma.202202169

Reactive Oxygen Species Scavenging Nanomedicine for the Treatment of Ischemic Heart Disease

There has been an increasing demand for the development of nanocarriers targeting multiple diseases with a broad range of properties. Due to their tiny size, giant surface area and feasible targetability, nanocarriers have optimized efficacy, decreased side effects and improved stability over conventional drug dosage forms. There are diverse types of nanocarriers that have been synthesized for drug delivery, including dendrimers, liposomes, solid lipid nanoparticles, polymersomes, polymer–drug conjugates, polymeric nanoparticles, peptide nanoparticles, micelles, nanoemulsions, nanospheres, nanocapsules, nanoshells, carbon nanotubes and gold nanoparticles, etc. Several characterization techniques have been proposed and used over the past few decades to control and predict the behavior of nanocarriers both in vitro and in vivo. In this review, we describe some fundamental in vitro, ex vivo, in situ and in vivo characterization methods for most nanocarriers, emphasizing their advantages and limitations, as well as the safety, regulatory and manufacturing aspects that hinder the transfer of nanocarriers from the laboratory to the clinic. Moreover, integration of artificial intelligence with nanotechnology, as well as the advantages and problems of artificial intelligence in the development and optimization of nanocarriers, are also discussed, along with future perspectives.

/pdf/nanocarrier-drug-delivery-systems-characterization-18whgjgs.pdf

Nanocarrier Drug Delivery Systems: Characterization, Limitations, Future Perspectives and Implementation of Artificial Intelligence

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

Shailaja Patel

Papers

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