Figure 6 - uploaded by Kopparam Manjunath
Content may be subject to copyright.
Mean nitrendipine concentration-time profiles in organs after i.v. administration of NDP-Susp, NDP-TP, NDP-TP-DCP and NDP-TP-SA (10 mg kg 21 ) to mice (n ¼ 3): (a) Serum, (b) Heart, (c) Brain, (d) Liver, (e) Spleen and (f) Kidney.
Source publication
The aim of this research was to study whether the bioavailability of nitrendipine (NDP) could be improved by administering nitrendipine solid lipid nanoparticles (SLN) duodenally to rats.
Nitrendipine was incorporated into SLN prepared by hot homogenization followed by ultrasonication method. SLN were produced using various triglycerides (trimyrist...
Contexts in source publication
Context 1
... standard curves having nitrendipine concentrations ranging from 0.1 to 2.4 mg gm 21 exhibited good linearity and correlation co-efficients over this concentration range were 0.9957 to 0.9995 (n ¼ 3), for all measured organs. Figure 6(a -f) show the concentrations of nitrendipine (in serum, heart, brain, liver, spleen and kidney, respectively) vs. time curves after i.v. administration of three kinds of NDP-SLNs and suspension. ...
Context 2
... showed enhanced brain concentrations of nitrendipine and maintained high drug levels for 6 h ( Figure 6(c)) whereas the drug levels were maintained for 3 h only with NDP-Susp. Compared to the NDP- Susp, C max (highest brain concentration) of SLNs increased by 3.2, 7.3 and 9.1 times for NDP-TP, NDP-TP-DCP and NDP-TP-SA, respectively. ...
Citations
... Dopamine levels were found to be higher, particularly in the animal brains, indicating successful brain targeting and fewer off-target effects. Nitrendipine-loaded solid-lipid nanoparticles (SLNs) were created by Manjunath and Venkateswarlu to treat dementia brought on by Huntington's disease (Manjunath and Venkateswarlu, 2006). Compared to the free drug, the SLNs that had been properly produced showed increased drug-brain uptake and decreased dementia occurrences. ...
... A study was conducted in which SLNs of nitrendipine were prepared, and a comparison of the uptake of nano-formulation and the bulk drug was carried out. According to the findings, the drug was taken in at a higher rate when it was encapsulated in SLNs [235]. ...
The neurodegenerative condition known as Parkinson’s disease (PD) is brought on by the depletion of dopaminergic neurons in the basal ganglia, which is the brain region that controls body movement. PD occurs due to many factors, from which one of the acknowledged effects of oxidative stress is pathogenic pathways that play a role in the development of Parkinson’s disease. Antioxidants, including flavonoids, vitamins E and C, and polyphenolic substances, help to reduce the oxidative stress brought on by free radicals. Consequently, this lowers the risk of neurodegenerative disorders in the long term. Although there is currently no cure for neurodegenerative illnesses, these conditions can be controlled. The treatment of this disease lessens its symptoms, which helps to preserve the patient’s quality of life. Therefore, the use of naturally occurring antioxidants, such as polyphenols, which may be obtained through food or nutritional supplements and have a variety of positive effects, has emerged as an appealing alternative management strategy. This article will examine the extent of knowledge about antioxidants in the treatment of neurodegenerative illnesses, as well as future directions for research. Additionally, an evaluation of the value of antioxidants as neuroprotective agents will be provided.
Keywords: neurodegeneration; antioxidants; phytoconstituents; polyphenols; Parkinson’s disease
... A study was conducted in which SLNs of nitrendipine were prepared, and a comparison of the uptake of nano-formulation and the bulk drug was carried out. According to the findings, the drug was taken in at a higher rate when it was encapsulated in SLNs [235]. ...
The neurodegenerative condition known as Parkinson’s disease (PD) is brought on by the depletion of dopaminergic neurons in the basal ganglia, which is the brain region that controls body movement. PD occurs due to many factors, from which one of the acknowledged effects of oxidative stress is pathogenic pathways that play a role in the development of Parkinson’s disease. Antioxidants, including flavonoids, vitamins E and C, and polyphenolic substances, help to reduce the oxidative stress brought on by free radicals. Consequently, this lowers the risk of neurodegenerative disorders in the long term. Although there is currently no cure for neurodegenerative illnesses, these conditions can be controlled. The treatment of this disease lessens its symptoms, which helps to preserve the patient’s quality of life. Therefore, the use of naturally occurring antioxidants, such as polyphenols, which may be obtained through food or nutritional supplements and have a variety of positive effects, has emerged as an appealing alternative management strategy. This article will examine the extent of knowledge about antioxidants in the treatment of neurodegenerative illnesses, as well as future directions for research. Additionally, an evaluation of the value of antioxidants as neuroprotective agents will be provided.
... It also brings new opportunities for various excipients that are emerging as bioactive recently in the last decade [76]. Further, excipients such as Cremophor EL and pluronic polymers have been shown to decrease chylomicron production and reduce the P-gp efflux transport of drug molecules [77,78]. One of the versatile excipients in this category is tween 80 which has been found as excellent solubilizer, inhibitor of P-gp efflux and increase chylomicron production [76,79]. ...
The drug administered by an oral route has to withstand a harsh environment of gastrointestinal media, absorb through intestinal epithelium and circumvent first-pass metabolism in liver before reaching portal blood circulation. Moreover, hydrophobic drug molecules offer challenges for formulation with respect to their solubility and hence bioavailability. Various approaches have been developed to overcome this barrier. One of them is the use of lipids in formulation. Incorporation of the drug in lipids can result in increased solubility, absorption and thereby enhanced bioavailability. Intestinal lymphatic route of absorption has also been explored for increasing bioavailability of hydrophobic drug moieties. In this chapter, we have discussed the pathway of lipid digestion in the human body as well as the mechanism of lipid particles upon oral administration. The various lipid formulations developed and the excipients used in the formulations have also been described. The importance of lipid chain length and the effect of food in increasing the bioavailability of drug is discussed. The lymphatic pathway of lipid carriers has also been discussed.
... To obtain target-specific delivery of medications across the BBB, the technique described above has been utilised for the encapsulation of a wide variety of pharmaceuticals. After intravenous and intraduodenal injection, it has been shown that sterylamine-based SLNs carrying clozapine, an antipsychotic medicine, can effectively deliver the pharmaceutical into the brain [265]. Additional examples of drug-laden SLNs are atazanavir-packed SLNs for the treatment of HIV encephalitis and quercetin-loaded SLNs for the treatment of Alzheimer's disease [266,267]. ...
Artificial, de-novo manufactured materials (with controlled nano-sized characteristics) have been progressively used by neuroscientists during the last several decades. The introduction of novel implantable bioelectronics interfaces that are better suited to their biological targets is one example of an innovation that has emerged as a result of advanced nanostructures and implantable bioelectronics interfaces, which has increased the potential of prostheses and neural interfaces. The unique physical–chemical properties of nanoparticles have also facilitated the development of novel imaging instruments for advanced laboratory systems, as well as intelligently manufactured scaffolds and microelectrodes and other technologies designed to increase our understanding of neural tissue processes. The incorporation of nanotechnology into physiology and cell biology enables the tailoring of molecular interactions. This involves unique interactions with neurons and glial cells in neuroscience. Technology solutions intended to effectively interact with neuronal cells, improved molecular-based diagnostic techniques, biomaterials and hybridized compounds utilized for neural regeneration, neuroprotection, and targeted delivery of medicines as well as small chemicals across the blood–brain barrier are all purposes of the present article.
... One other disadvantage of solid NPs is their relatively low drug loading efficiency [34] and problems with drug expulsion, making controlled release challenging with these NPs [35]. Prior studies revealed that 2-7% of intravenously injected solid lipid NPs, with a formulation similar to that used in this study, pass into the brain parenchyma, although this percentage varies depending on the properties of the prepared lipid NPs [36,37]. Lipid NPs pass through the BBB via passive diffusion, active transport, endocytosis and the paracellular pathway [36,38,39]. ...
... Prior studies revealed that 2-7% of intravenously injected solid lipid NPs, with a formulation similar to that used in this study, pass into the brain parenchyma, although this percentage varies depending on the properties of the prepared lipid NPs [36,37]. Lipid NPs pass through the BBB via passive diffusion, active transport, endocytosis and the paracellular pathway [36,38,39]. Active targeting of NPs can also be achieved by conjugating them with various ligands, such as cationic bovine serum albumin, thereby enabling transcytosis through the BBB [40]. ...
Background: A requirement for nanoparticle (NP) research is visualization of particles within cells and tissues. Limitations of electron microscopy and low yields of NP fluorescent tagging warrant the identification of alternative imaging techniques. Method: Confocal reflectance microscopy (CRM) in combination with fluorescence imaging was assessed for visualizing rhodamine B-conjugated silver and fluorescein isothiocyanate-conjugated lipid core-stearylamine NP uptake in vitro and in vivo. Results: CRM successfully identified cellular uptake and blood–brain barrier penetration of NPs owing to their distinguishing refractive indices. NP-dependent reflectance signals in vitro were dose and incubation time dependent. Finally, CRM facilitated the distinction between nonspecific fluorescence signals and NPs. Conclusion: These findings demonstrate the value of CRM for NP visualization in tissues, which can be performed with a standard confocal microscope.
... Some of the previous studies performed to enhance the oral bioavailability of drugusing SLNs are listed in Table 1. [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] In a recent study, SLNs were prepared through acoustic cavitation assisted hot melt mixing technique for controlled release and enhanced the oral bioavailability of fenofibrate, ibuprofen, ketoprofen, and nabumetone. The prepared tristearin based SLNs were of less than 350 nm particle size having high entrapment efficiency (>80%). ...
To date, the oral route is considered as a proffered route for drug delivery having high patient compliance. However, the therapeutic efficacy of the drug given through the oral route is hampered by its low solubility, low bioavailability, and stability issues in the harsh gastric environment. Solid lipid nanoparticles (SLNs) have emerged as a potential system that can overcome the oral bioavailability issues associated with poorly water-soluble drugs. The SLNs have both properties of lipid emulsion and polymeric nanoparticles and thus offer various benefits, such as high biocompatibility, biodegradability, protect the drug from degradation, improved drug stability in gastrointestinal tract, controlled drug release, avoid organic solvents, and ease of manufacturing. This review discussed the recent advancements in SLNs with regards to the oral bioavailability of poorly water-soluble drugs. The key components and methods of preparation of SLNs were also discussed. To conclude, studies performed to date have shown promising results with SLNs in enhancing the oral bioavailability of poorly water-soluble drugs with a high degree of biocompatibility.
... In the context of HD treatment, Manjunath and Venkateswarlu prepared SLNs loaded with nitrendipine, and their pharmacokinetics and bioavailability were assessed after intravenous and intraduodenal administration to male Wistar rats [433]. SLNs were composed of various triglycerides (trimyristin, tripalmitin and tristearin), soy PC 95%, poloxamer 188, and charge modifiers (dicetyl phosphate and stearylamine). ...
... Z-potential values were found to be highly negative in the absence of charge modifiers or in the presence of the dicetyl phosphate as lipid. On the contrary, the use of stearylamine gave, in all cases, a net positive surface charge [433]. Compared to the nitrendipine suspension, which presented an elevated drug concentration in the brain over 3 h, nitrendipine-loaded SLNs showed a high drug amount for at least 6 h. ...
... Compared to the nitrendipine suspension, which presented an elevated drug concentration in the brain over 3 h, nitrendipine-loaded SLNs showed a high drug amount for at least 6 h. In particular, after intraduodenal administration, positively charged SLNs improved the bioavailability of nitrendipine from 3to 5-fold, independently from the specific triglyceride used [433]. When compared with nitrendipine suspension, SLNs were better taken up by brain and moderately taken up by heart, liver, and spleen after intravenous administration. ...
Neurodegenerative diseases (NDs) represent a heterogeneous group of aging-related disorders featured by progressive impairment of motor and/or cognitive functions, often accompanied by psychiatric disorders. NDs are denoted as ‘protein misfolding’ diseases or proteinopathies, and are classified according to their known genetic mechanisms and/or the main protein involved in disease onset and progression. Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD) are included under this nosographic umbrella, sharing histopathologically salient features, including deposition of insoluble proteins, activation of glial cells, loss of neuronal cells and synaptic connectivity. To date, there are no effective cures or disease-modifying therapies for these NDs. Several compounds have not shown efficacy in clinical trials, since they generally fail to cross the blood-brain barrier (BBB), a tightly packed layer of endothelial cells that greatly limits the brain internalization of endogenous substances. By engineering materials of a size usually within 1–100 nm, nanotechnology offers an alternative approach for promising and innovative therapeutic solutions in NDs. Nanoparticles can cross the BBB and release active molecules at target sites in the brain, minimizing side effects. This review focuses on the state-of-the-art of nanoengineered delivery systems for brain targeting in the treatment of AD, PD and HD.
... For example, polymeric nanoparticles, liposomes, and regular oil-in-water (o/w) emulsions have advantages that lipid nanoparticles (SLNs and NLCs) do not have. Particles with diameters between 120 and 200 nm are seldom cleared by RES cells, preventing liver and spleen filtration [92], and various release profiles may be obtained since the API is inserted into the lipid matrix [94][95][96]. Particles with longer circulation times and hence greater ability to target the site of interest should be 120-200 nm in diameter and have a hydrophilic surface (external hydrophilic polymer corona) in order to reduce the clearance by macrophages. ...
Polymeric lipid hybrid nanoparticles (PLNs) are core–shell nanoparticles made up of a polymeric kernel and lipid/lipid–PEG shells that have the physical stability and biocompatibility of both polymeric nanoparticles and liposomes. PLNs have emerged as a highly potent and promising nanocarrier for a variety of biomedical uses, including drug delivery and biomedical imaging, owing to recent developments in nanomedicine. In contrast with other forms of drug delivery systems, PLNs have been regarded as seamless and stable because they are simple to prepare and exhibit excellent stability. Natural, semi-synthetic, and synthetic polymers have been used to make these nanocarriers. Due to their small scale, PLNs can be used in a number of applications, including anticancer therapy, gene delivery, vaccine delivery, and bioimaging. These nanoparticles are also self-assembled in a reproducible and predictable manner using a single or two-step nanoprecipitation process, making them significantly scalable. All of these positive attributes therefore make PLNs an attractive nanocarrier to study. This review delves into the fundamentals and applications of PLNs as well as their formulation parameters, several drug delivery strategies, and recent advancements in clinical trials, giving a comprehensive insight into the pharmacokinetic and biopharmaceutical aspects of these hybrid nanoparticles.
... The permeability of the drug molecules to the brain site can be improved by BBB-active drug efflux transporters based on the efflux mechanism. Manjunath and Venkateswarlu [76] tried to improve the bioavailability of the antipsychotic drugs clozapine and nitrendipine through their various SLN formulations, using PEG and Tween 80. 5-fluoro-2′-deoxyuridine (FUdR) to the brain, 3′,5′-dioctanoyl-5-fluoro-2′-deoxyuridine (DO-FUdR) incorporated into solid lipid nanoparticles (DO-FUdR-SLN), has shown good brain-targeting efficacy for CNS disorders, shown in the studies by Wang et al. [77]. The mechanism behind the enhanced drug bioavailability could be explained by: ...
The blood-brain barrier (BBB) plays a vital role in the protection and maintenance of homeostasis in the brain. In this way, it is an interesting target as an interface for various types of drug delivery, specifically in the context of the treatment of several neuropathological conditions where the therapeutic agents cannot cross the BBB. Drug toxicity and on-target specificity are among some of the limitations associated with current neurotherapeutics. In recent years, advances in nanodrug delivery have enabled the carrier system containing the active therapeutic drug to target the signaling pathways and pathophysiology that are closely linked to central nervous system (CNS) disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Hunting-ton's disease (HD), multiple sclerosis (MS), brain tumor, epilepsy, ischemic stroke, and neuro-degeneration. At present, among the nano formulations, solid lipid nanoparticles (SLNs) have emerged as a putative drug carrier system that can deliver the active therapeutics (drug-loaded SLNs) across the BBB at the target site of the brain, offering a novel approach with controlled drug delivery, longer circulation time, target specificity, and higher efficacy, and more importantly, reducing toxicity in a biomimetic way. This paper highlights the synthesis and application of SLNs as a novel nontoxic formulation strategy to carry CNS drugs across the BBB to improve the use of therapeutics agents in treating major neurological disorders in future clinics.
