In-vivo pharmacokinetic study of ibrutinib-loaded nanostructured lipid carriers in rat plasma by sensitive spectrofluorimetric method using harmonized approach of quality by design and white analytical chemistry.

Ibrutinib, an antineoplastic agent tackling chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's Macroglobulinemia, falls under the category of BCS class II drugs, characterized by a puzzling combination of low solubility and high permeability. Its oral bioavailability remains a perplexing challenge, merely reaching 2.9 % due to formidable first-pass metabolism hurdles. In a bid to surmount this obstacle, researchers embarked on a journey to develop ibrutinib-loaded NLCs (Nanostructured Lipid Carriers) using a methodology steeped in complexity: a Design of Experiments (DoE)-based hot melted ultrasonication approach. Despite a plethora of methods for analyzing ibrutinib in various matrices, the absence of a spectrofluorimetric method for assessing it in rat plasma added to the enigma. Thus emerged a spectrofluorimetric method, embodying principles of white analytical chemistry and analytical quality by design, employing a Placket-Burman design for initial method exploration and a central composite design for subsequent refinement. This method underwent rigorous validation in accordance with ICH guidelines, paving the way for its application in scrutinizing the in-vivo pharmacokinetics of ibrutinib-loaded NLCs, juxtaposed against commercially available formulations. Surprisingly, the optimized NLCs exhibited a striking 1.82-fold boost in oral bioavailability, shedding light on their potential efficacy. The environmental impact of this method was scrutinized using analytical greenness tools, affirming its eco-friendly attributes. In essence, the culmination of these efforts has not only propelled advancements in drug bioavailability but also heralded the dawn of a streamlined and environmentally conscious analytical paradigm.

Treatment of endometriosis with mifepristone mediated by nanostructured lipid carriers.

Mifepristone, a progesterone receptor antagonist, was initially used to terminate early pregnancy. As scientific research advanced, it emerged to be effective in the treatment of various tumors and tumor-like conditions such as endometriosis. Despite the therapeutic potential of mifepristone, its therapeutic effect is still far from ideal because the drug is difficult to dissolve and to accumulate in the target tissue sites. To address this issue, mifepristone-loaded nanostructured lipid carriers (Mif-NLC) were prepared by a simple solvent diffusion method and their anti-endometriosis performance and mechanisms were initially investigated. By optimizing the preparation protocol, we obtained uniform and spheroidal Mif-NLC with an average particle size of 280 nm. The encapsulation rate and drug loading capacity were 64.67% ± 0.15% and 2.7% ± 0.014%, respectively, as measured by UV spectrophotometry. The in vitro release kinetics indicated that mifepristone was released from NLC in a sustained-release manner. Compared with free mifepristone, Mif-NLC exhibited enhanced cellular uptake and inhibition of invasion activity in primary mesenchymal cells of endometriosis. A certain reduction in the size of endometriotic cysts was observed in animals compared to controls. The induction of autophagy via Mif-NLC may serve as the molecular mechanism underlying this effect. Furthermore, observation of uterine structures showed negligible toxic effects. This suggested that mifepristone encapsulated in NLC can improve its bioavailability and anti-endometriosis efficacy, which provided a new strategy for the treatment of endometriosis.

Exploration of Abiraterone acetate loaded Nanostructured lipid carriers for bioavailability improvement and circumvention of fast-fed variability.

Abiraterone acetate (ABA), a biopharmaceutical class IV drug suffers from solubility and permeability pitfalls resulting in limited oral bioavailability and positive food effect, i.e. multi-fold enhancement in drug absorption in the presence of food. This poses difficulties to physicians towards the estimation of dose and dosage regimen required for efficacious therapy of prostate cancer (PCa). Nanostructured lipid carriers (NLC) have demonstrated tremendous outcomes in enhancing the oral bioavailability of various entities along with food effect attenuation. In this study, Quality by design and multivariate analysis was employed for optimization of ABA loaded NLC (ABA NLC). The optimal size, PDI and zeta potential obtained using QbD were 134.6 nm, 0.163 and -15.7 mV respectively. Ex vivo qualitative and quantitative intestinal permeability studies demonstrated improved traversion of NLC through the intestinal segments. In vitro dissolution profile in biorelevant fast and fed gastric and intestinal media revealed minimal differences for ABA NLC compared to ABA. In vivo pharmacokinetics was performed to decipher the efficacy of ABA NLC in mitigating the food effect of ABA. The studies demonstrated 14.51-fold and 1.94-fold improvement in oral bioavailability during fasted and fed state respectively as compared to free ABA. The absorption mechanism of ABA NLC using chylomicron flow blocking approach conveyed lymphatic uptake as the major mechanism. Cmax fast/fed ratio was 0.9758 whereas, AUC fast/fed ratio was 0.9386, which being nearly equivalent, confirmed the food effect attenuation. Therefore, the results of the study demonstrate optimal pharmacokinetics of ABA NLC and its utility in circumventing the fast fed variability.

Nanoparticles and Their Applications in Lipid Signaling.

This chapter provides an overview of the diverse range of applications associated with nanoparticles. The application of nanoparticles in the medical field has garnered considerable attention due to their unique properties and versatile compositions. They have shown promise in the treatment of cancer, fungal and viral infections, and pain management. These systems provide numerous benefits, such as increased drug stability, improved bioavailability, and targeted delivery to specific tissues or cells. The objective of this chapter is to provide a brief analysis of the differences between nanoparticles and lipid particles, focusing particularly on the importance of nanoparticle size and composition in their interactions with lipids. Additionally, the applications of nanoparticles in lipid signaling will be discussed, considering the vital roles lipids play in cellular signaling pathways. Nanoparticles have shown immense potential in the regulation and control of medical pathways. In this case, we will focus on the manufacture of liposomes, a type of nanoparticle composed of lipids. The reason behind the extensive investigation into liposomes as drug delivery vehicles is their remarkable biocompatibility and adaptability. This section will provide insights into the methods and techniques employed for liposome formulation.

Intranasal delivery of doxepin: enhancing brain targeting efficiency utilizing nanostructured lipid carriers for a biopharmaceutics drug disposition classification system class-I drug.

Doxepin, a Class-I Biopharmaceutics Drug Disposition Classification System (BDDCS) drug, exhibits poor bioavailability due to extensive first-pass metabolism. This research focuses on enhancing the delivery of doxepin by formulating nanostructured lipid carriers (NLCs) through the utilization of the Box-Behnken Design methodology. These optimized NLCs are intended for intranasal administration, with the ultimate goal of improving nose-to-brain drug delivery. NLCs were formulated using a high-speed homogenization technique. The optimized batch had a small particle size (75.80 ± 5.48 nm, PDI = 0.286), high entrapment efficiency (94.10 ± 0.16%), and sustained ex vivo release (82.25 ± 4.61% at 24 h). Characterization studies confirmed the conversion of doxepin from a crystalline to an amorphous state with uniform distribution in the lipid matrix. In vivo pharmacokinetic studies in rats showed significantly higher doxepin concentration in the brain tissue (Cmax = 16.77 µg/g, tmax = 30 min) after intranasal administration compared to intravenous administration (Cmax = 2.53 µg/g, tmax = 6 h). High-drug targeting efficiency (DTE = 284.3%) and direct transport percentage (DTP = 64.8%) suggested direct penetration of NLCs in the brain via olfactory and trigeminal pathways. In conclusion, the study highlights the potential of NLCs to improve the bioavailability of doxepin through nose-to-brain delivery and thereby potentially enable the treatment of neurological disorders.

Nanostructured lipid carriers promote percutaneous absorption and hair follicle targeting of tofacitinib for treating alopecia areata.

Alopecia areata affects over 140 million people worldwide and causes severe psychological distress. The Janus kinase (JAK) inhibitor, tofacitinib, shows significant potential in therapeutic applications for treating alopecia areata; however, the systemic adverse effects of oral administration and low absorption rate at the target site limit its application. Hence, to address this issue, we designed topical formulations of tofacitinib-loaded cationic lipid nanoparticles (TFB-cNLPs) with particle sizes of approximately 200 nm. TFB-cNLPs promoted percutaneous absorption and hair follicle targeting in an ex vivo pig ear model. TFB-cNLP decreased IFN-γ-induced alopecia areata symptoms in an in vitro follicle model by blocking the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. It also reduced the number of CD8+NKG2D+T cells in a C3H mouse model of alopecia areata in vivo, thereby inhibiting the progression of alopecia areata and reversing hair loss. These findings suggest that TFB-cNLP enhanced hair follicle targeting and has the potential for topical treatment or prevention of alopecia areata.

On the Structure, Stability, and Cell Uptake of Nanostructured Lipid Carriers for Drug Delivery.

The efficacy of nanostructured lipid carriers (NLC) for drug delivery strongly depends on their stability and cell uptake. Both properties are governed by their compositions and internal structure. To test the effect of the lipid composition of NLC on cell uptake and stability, three kinds of liquid lipids with different degrees of unsaturation are employed. After ensuring homogeneous size distributions, the thermodynamic characteristics, stability, and mixing properties of NLC are characterized. Then the rates and predominant pathways of cell uptake are determined. Although the same surfactant is used in all cases, different uptake rates are observed. This finding contradicts the view that the surface properties of NLC are dominated by the surfactant. Instead, the uptake rates are explained by the structure of the nanocarrier. Depending on the mixing properties, some liquid lipids remain inside the nanocarrier, while other liquid lipids are present on the surface. Nanocarriers with liquid lipids on the surface are taken up more readily by the cells. This shows that the engineering of efficient lipid nanocarriers requires a delicate balance of interactions between all components of the nanocarrier on the molecular level.

Box-Behnken Design-Based Optimization and Evaluation of Lipid-Based Nano Drug Delivery System for Brain Targeting of Bromocriptine.

Bromocriptine (BCR) presents poor bioavailability when administered orally because of its low solubility and prolonged first-pass metabolism. This poses a significant challenge in its utilization as an effective treatment for managing Parkinson's disease (PD). The utilization of lipid nanoparticles can be a promising approach to overcome the limitations of BCR bioavailability. The aim of the research work was to develop and evaluate bromocriptine-loaded solid lipid nanoparticles (BCR-SLN) and bromocriptine-loaded nanostructured lipid carriers (BCR-NLC) employing the Box-Behnken design (BBD). BCR-SLNs and BCR-NLCs were developed using the high-pressure homogenization method. The prepared nanoparticles were characterized for particle size (PS), polydispersity index (PDI), and entrapment efficiency (EE). In vitro drug release, cytotoxicity studies, in vivo plasma pharmacokinetic, and brain distribution studies evaluated the optimized lipid nanoparticles. The optimized BCR-SLN had a PS of 219.21 ± 1.3 nm, PDI of 0.22 ± 0.02, and EE of 72.2 ± 0.5. The PS, PDI, and EE of optimized BCR-NLC formulation were found to be 182.87 ± 2.2, 0.16 ± 0.004, and 83.57 ± 1.8, respectively. The in vitro release profile of BCR-SLN and BCR-NLC showed a biphasic pattern, immediate release, and then trailed due to the sustained release. Furthermore, a pharmacokinetic study indicated that both the optimized BCR-SLN and BCR-NLC formulations improve the plasma and brain bioavailability of the drug compared to the BCR solution. Based on the research findings, it can be concluded that the BCR-loaded lipid nanoparticles could be a promising carrier by enhancing the BBB penetration of the drug and helping in the improvement of the bioavailability and therapeutic efficacy of BCR in the management of PD.

Lipid-Based Nanomedicine for Alzheimer's Disease: A Comprehensive Review of Recent Advances.

BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia and is expected to greatly rise in future, making it a major worldwide health concern with severe impacts on individuals and society. Despite advancements in understanding the cellular and molecular aspects of Alzheimer's disease (AD) in recent decades, it still poses a significant problem. A major problem is accurately delivering drugs to diseased neurons while minimising effects on healthy neurons. This difficulty is worsened by the low water solubility of anti-Alzheimer's disease medicines and the blood-brain barrier (BBB) that hinders the entry of central nervous system pharmaceuticals that are highly lipophilic. OBJECTIVE: The focus of this article is on nanocarriers that are lipid-based. This is one of the more widely accepted methods of treating Alzheimer's disease, as it increases therapeutic efficacy while decreasing side effects related to cooperated neurological disorder payload. METHOD: Searched many databases for papers published under the title (including PubMed, Elsevier, and Google Scholar). RESULTS/CONCLUSION: Nano Lipid Carriers (NLCs) are recognized for their ability to target the brain effectively due to their lipid-loving properties and compatibility with living tissues. They improve the absorption of drugs in the brain while decreasing the accumulation of drugs in unintended organs. This work emphasises the importance of nano lipid carriers, which are lipophilic and biocompatible and have demonstrated exceptional targeting efficiency, making them an ideal carrier system for delivering medications to the brain.

Effect of Cremophor RH40, Hydroxypropyl Methylcellulose, and Mixing Speed on Physicochemical Properties of Films Containing Nanostructured Lipid Carriers Loaded with Furosemide Using the Box-Behnken Design.

This study aimed to examine the characteristics of H-K4M hydroxypropyl methylcellulose (HPMC) films containing nanostructured lipid carriers (NLCs) loaded with furosemide. A hot homogenization technique and an ultrasonic probe were used to prepare and reduce the size of the NLCs. Films were made using the casting technique. This study used a Box-Behnken design to evaluate the influence of three key independent variables, specifically H-K4M concentration (X1), surfactant Cremophor RH40 concentration (X2), and mixing speed (X3), on the physicochemical properties of furosemide-loaded NLCs and films. The furosemide-loaded NLCs had a particle size ranging from 54.67 to 99.13 nm, and a polydispersity index (PDI) ranging from 0.246 to 0.670. All formulations exhibited a negative zeta potential, ranging from -7.05 to -5.61 mV. The prepared films had thicknesses and weights ranging from 0.1240 to 0.2034 mm and 0.0283 to 0.0450 g, respectively. The drug content was over 85%. Film surface wettability was assessed based on the contact angle, ranging from 32.27 to 68.94°. Film tensile strength varied from 1.38 to 7.77 MPa, and their elongation at break varied from 124.19 to 170.72%. The ATR-FTIR analysis confirmed the complete incorporation of the drug in the film matrix. Therefore, the appropriate selection of values for key parameters in the synthesis of HPMC films containing drug-loaded NLCs is important in the effective development of films for medical applications.

Charge-switchable cell-penetrating peptides for rerouting nanoparticles to glioblastoma treatment.

Glioblastoma (GB) is one of the most lethal types of neoplasms with unique anatomic, physiologic, and pathologic features that usually persist after exposure to standard therapeutic modalities. It is biologically aggressive, and the existence of the blood-brain barrier (BBB) limits the efficacy of standard therapies. In this work, we hypothesize the potential of surface-functionalized ultra-small nanostructured lipid carriers (usNLCs) with charge-switchable cell-penetrating peptides (CPPs) to overcome this biological barrier and improve targeted delivery to brain tumor tissues. The big question is: what is the potential of CPPs in directing nanoparticles toward brain tumor tissue? To answer this question, the usNLCs were functionalized with distinct biomolecules [five CPPs, c(RGDfK) and transferrin, Tf] through electrostatic interaction and its ability as a targeting approach to BBB (HBMEC) and glioma cells (U87 cells) evaluated in terms of physicochemical properties, cellular uptake, permeability in a 2D-BBB model, and tumor growth inhibition. Monte Carlo simulations elucidated CPP adsorption patterns. The permeability studies revealed that targeted usNLCs, especially usNLCsTf and usNLCsCPP4, exhibited an increased permeability coefficient compared to the non-targeted usNLCs. Functionalized usNLCs evidenced enhanced uptake in BBB cells, with smaller CPPs showing higher internalization (CPP1 and CPP2). Similarly, functionalized usNLCs exhibited more significant cytotoxicity in glioma cells, with specific CPPs promoting favorable internalization. Analysis of the endocytic pathway indicated that usNLCsCPPs were mainly internalized by direct translocation and caveolae-mediated endocytosis. Optimal usNLCs with dual targeting capabilities to both BBB and GB cells provide a promising therapeutic strategy for GB.

The effect of physical stability and modified gastrointestinal tract behaviour of resveratrol-loaded NLCs encapsulated alginate beads.

Nanostructured lipid carriers (NLC) have low storage and gastrointestinal stability, limiting their applicability. The work aimed to elevate the stability and behaviour of NLC in the alimentary tract by creating an alginate bead. Through the extrusion dropping procedure, Resveratrol (RES)-loaded NLC were efficiently integrated into alginate beads. The incorporation had no significant impact on the particle size, morphology, or inner structure of NLC, as assessed using DLS (Dynamic Light Scattering), SEM (Scanning Electron Microscopy), Differential Scanning Calorimetry (DSC) and FT-IR (Fourier Transform Infra-Red). Incorporating NLC into alginate beads improves its physical stability compared to dispersion of NLC as well as NLC-Sol. An in vitro release investigation found that the NLC-alginate beads released RES more slowly than optimized NLC formulation (RES-NLCs-opt) and NLC-alginate sol. Research on simulated in vitro digestive models revealed that just a small amount of integrated NLC may permeate stomach fluid due to its tiny size. The slow diffusion of NLC from alginate to intestinal fluid prevented aggregation and allowed for gentle hydrolysis of the lipid matrix. Incorporating NLC in alginate beads shows promise for improving stability, modifying gastrointestinal behaviour, and controlling release throughout the process of digestion.

Improvement of lidocaine skin permeation by using passive and active enhancer methods.

Lidocaine is generally recognized and preferred for local anaesthesia, but in addition, studies have described additional benefits of lidocaine in cancer therapy, inflammation reduction, and wound healing. These properties contribute to its increasing importance in dermatological applications, and not only in pain relief but also in other potential therapeutic outcomes. Therefore, the purpose of our study was to enhance lidocaine delivery through the skin. A stable nanostructured lipid carrier (NLC), as a passive permeation enhancer, was developed using a 23 full factorial design. The nanosystems were characterized by crystallinity behaviour, particle size, zeta potential, encapsulation efficiency measurements, and one of them was selected for further investigation. Then, NLC gel was formulated for dermal application and compared to a traditional dermal ointment in terms of physicochemical (rheological behaviour) and biopharmaceutical (qualitative Franz diffusion and quantitative Raman investigations) properties. The study also examined the use of 3D printed solid microneedles as active permeation enhancers for these systems, offering a minimally invasive approach to enhance transdermal drug delivery. By actively facilitating drug permeation through the skin, microneedles can complement the passive transport achieved by NLCs, thereby providing an innovative and synergistic approach to improving lidocaine delivery.

Engineering mannose-functionalized nanostructured lipid carriers by sequential design using hybrid artificial intelligence tools.

Nanostructured lipid carriers (NLCs) hold significant promise as drug delivery systems (DDS) owing to their small size and efficient drug-loading capabilities. Surface functionalization of NLCs can facilitate interaction with specific cell receptors, enabling targeted cell delivery. Mannosylation has emerged as a valuable tool for increasing the ability of nanoparticles to be recognized and internalized by macrophages. Nevertheless, the design and development of functionalized NLC is a complex task that entails the optimization of numerous variables and steps, making the process challenging and time-consuming. Moreover, no previous studies have been focused on evaluating the functionalization efficiency. In this work, hybrid Artificial Intelligence technologies are used to help in the design of mannosylated drug loaded NLCs. Artificial neural networks combined with fuzzy logic or genetic algorithms were employed to understand the particle formation processes and optimize the combinations of variables for the different steps in the functionalization process. Mannose was chemically modified to allow, for the first time, functionalization efficiency quantification and optimization. The proposed sequential methodology has enabled the design of a robust procedure for obtaining stable mannosylated NLCs with a uniform particle size distribution, small particle size (< 100 nm), and a substantial positive zeta potential (> 20mV). The incorporation of mannose on the surfaces of these DDS following the established protocols achieved > 85% of functionalization efficiency. This high effectiveness should enhance NLC recognition and internalization by macrophages, thereby facilitating the treatment of chronic inflammatory diseases.

Novel nanostructured lipid carriers loading Apigenin for anterior segment ocular pathologies.

Dry eye disease (DED) is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction and constitutes one of the most common ocular conditions worldwide. However, its treatment remains unsatisfactory. While artificial tears are commonly used to moisturize the ocular surface, they do not address the underlying causes of DED. Apigenin (APG) is a natural product with anti-inflammatory properties, but its low solubility and bioavailability limit its efficacy. Therefore, a novel formulation of APG loaded into biodegradable and biocompatible nanoparticles (APG-NLC) was developed to overcome the restricted APG stability, improve its therapeutic efficacy, and prolong its retention time on the ocular surface by extending its release. APG-NLC optimization, characterization, biopharmaceutical properties and therapeutic efficacy were evaluated. The optimized APG-NLC exhibited an average particle size below 200 nm, a positive surface charge, and an encapsulation efficiency over 99 %. APG-NLC exhibited sustained release of APG, and stability studies demonstrated that the formulation retained its integrity for over 25 months. In vitro and in vivo ocular tolerance studies indicated that APG-NLC did not cause any irritation, rendering them suitable for ocular topical administration. Furthermore, APG-NLC showed non-toxicity in an epithelial corneal cell line and exhibited fast cell internalization. Therapeutic benefits were demonstrated using an in vivo model of DED, where APG-NLC effectively reversed DED by reducing ocular surface cellular damage and increasing tear volume. Anti-inflammatory assays in vivo also showcased its potential to treat and prevent ocular inflammation, particularly relevant in DED patients. Hence, APG-NLC represent a promising system for the treatment and prevention of DED and its associated inflammation.

Enhanced In Vitro Antiviral Activity of Ivermectin-Loaded Nanostructured Lipid Carriers against Porcine Epidemic Diarrhea Virus via Improved Intracellular Delivery.

Porcine epidemic diarrhea virus (PEDV) is an acute enteric coronavirus, inducing watery diarrhea and high mortality in piglets, leading to huge economic losses in global pig industry. Ivermectin (IVM), an FDA-approved antiparasitic agent, is characterized by high efficacy and wide applicability. However, the poor bioavailability limits its application. Since the virus is parasitized inside the host cells, increasing the intracellular drug uptake can improve antiviral efficacy. Hence, we aimed to develop nanostructured lipid carriers (NLCs) to enhance the antiviral efficacy of IVM. The findings first revealed the capacity of IVM to inhibit the infectivity of PEDV by reducing viral replication with a certain direct inactivation effect. The as-prepared IVM-NLCs possessed hydrodynamic diameter of 153.5 nm with a zeta potential of -31.5 mV and high encapsulation efficiency (95.72%) and drug loading (11.17%). IVM interacted with lipids and was enveloped in lipid carriers with an amorphous state. Furthermore, its encapsulation in NLCs could enhance drug internalization. Meanwhile, IVM-NLCs inhibited PEDV proliferation by up to three orders of magnitude in terms of viral RNA copies, impeding the accumulation of reactive oxygen species and mitigating the mitochondrial dysfunction caused by PEDV infection. Moreover, IVM-NLCs markedly decreased the apoptosis rate of PEDV-induced Vero cells. Hence, IVM-NLCs showed superior inhibitory effect against PEDV compared to free IVM. Together, these results implied that NLCs is an efficient delivery system for IVM to improve its antiviral efficacy against PEDV via enhanced intracellular uptake.

A Novel Approach for Dermal Application of Pranoprofen-Loaded Lipid Nanoparticles for the Treatment of Post-Tattoo Inflammatory Reactions.

Recently, the number of people acquiring tattoos has increased, with tattoos gaining significant popularity in people between 20 and 40 years old. Inflammation is a common reaction associated with tattooing. The purpose of this study was to evaluate a nanostructured lipid carrier loading pranoprofen (PRA-NLC) as a tattoo aftercare formulation to reduce the inflammation associated with tattooing. In this context, the in vitro drug release and the ex vivo permeation-through-human-skin tests using Franz cells were appraised. The tolerance of our formulation on the skin was evaluated by studying the skin's biomechanical properties. In addition, an in vivo anti-inflammatory study was conducted on mice skin to evaluate the efficacy of the formulation applied topically after tattooing the animals. PRA-NLC showed a sustained release up to 72 h, and the amount of pranoprofen retained in the skin was found to be 33.48 µg/g/cm2. The formulation proved to be well tolerated; it increased stratum corneum hydration, and no signs of skin irritation were observed. Furthermore, it was demonstrated to be non-cytotoxic since the cell viability was greater than 80%. Based on these results, we concluded that PRA-NLC represents a suitable drug delivery carrier for the transdermal delivery of pranoprofen to alleviate the local skin inflammation associated with tattooing.

Rheological and Injectability Evaluation of Sterilized Poloxamer-407-Based Hydrogels Containing Docetaxel-Loaded Lipid Nanoparticles.

Nanostructured lipid carriers (NLCs) have the potential to increase the bioavailability and reduce the side effects of docetaxel (DTX). However, only a small fraction of nanoparticles given intravenously can reach a solid tumor. In situ-forming gels combined with nanoparticles facilitate local administration and promote drug retention at the tumor site. Injectable hydrogels based on poloxamer 407 are excellent candidates for this hybrid nanoparticle-hydrogel system because of their thermoresponsive behavior and biocompatibility. Therefore, this work aimed to develop injectable poloxamer hydrogels containing NLCs for intratumoral delivery of DTX. To ensure sterility, the obtained hydrogels were autoclaved (121 °C for 15 min) after preparation. Then, the incorporation of NLCs into the poloxamer hydrogels and the impact of steam sterilization on the nanocomposite hydrogels were evaluated concerning sol-gel transition, injectability, and physicochemical stability. All formulations were extruded through the tested syringe-needle systems with acceptable force (2.2-13.4 N) and work (49.5-317.7 N·mm) of injection. Following steam sterilization, injection became easier in most cases, and the physicochemical properties of all hydrogels remained practically unchanged according to the spectroscopical and thermal analysis. The rheological evaluation revealed that the nanocomposite hydrogels were liquid at 25 °C and underwent rapid gelation at 37 °C. However, their sterilized counterparts gelled at 1-2 °C above body temperature, suggesting that the autoclaving conditions employed had rendered these nanocomposite hydrogels unsuitable for local drug delivery.

Revolutionizing Wound Healing: Unleashing Nanostructured Lipid Carriers Embodied with Herbal Medicinal Plant.

Wound healing is crucial for maintaining skin integrity and preventing complications from external threats. Various plants, such as Achillea millefolium, Aloe vera, Curcuma longa, Calendula officinalis, Camellia sinensis, Azadirachta indica, and Plantago, have demonstrated wound healing capabilities and have been used in herbal medicine for wound care. NLCs are second-generation lipid nanoparticles, blending solid and liquid lipids to improve medication loading and limit leakage. NLCs have been used in various applications, including cosmeceuticals, chemotherapy, gene therapy, and brain targeting. Wound healing is divided into four stages: hemostasis, inflammatory response, proliferation, and remodeling. Factors such as age, gender, chronic disorders, and local agents like infections can affect recovery. These plants' antiinflammatory, antioxidant, and antibacterial activities have demonstrated potential in wound healing. Combining herbal medicinal plants and nanostructured lipid carriers (NLCs) can revolutionise wound treatment and improve overall healthcare outcomes.

Lipid-Based Nanoparticles as Oral Drug Delivery Systems: Overcoming Poor Gastrointestinal Absorption and Enhancing Bioavailability of Peptide and Protein Therapeutics.

Delivery and formulation of oral peptide and protein therapeutics have always been a challenge for the pharmaceutical industry. The oral bioavailability of peptide and protein therapeutics mainly relies on their gastrointestinal solubility and permeability which are affected by their poor membrane penetration, high molecular weight and proteolytic (chemical and enzymatic) degradation resulting in limited delivery and therapeutic efficacy. The present review article highlights the challenges and limitations of oral delivery of peptide and protein therapeutics focusing on the application, potential and importance of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) as lipid-based drug delivery systems (LBDDSs) and their advantages and drawbacks. LBDDSs, due to their lipid-based matrix can encapsulate both lipophilic and hydrophilic drugs, and by reducing the first-pass effect and avoiding proteolytic degradation offer improved drug stability, dissolution rate, absorption, bioavailability and controlled drug release. Furthermore, their small size, high surface area and surface modification increase their mucosal adhesion, tissue-targeted distribution, physiological function and half-life. Properties such as simple preparation, high-scale manufacturing, biodegradability, biocompatibility, prolonged half-life, lower toxicity, lower adverse effects, lipid-based structure, higher drug encapsulation rate and various drug release profile compared to other similar carrier systems makes LBDDSs a promising drug delivery system (DDS). Nevertheless, undesired physicochemical features of peptide and protein drug development and discovery such as plasma stability, membrane permeability and circulation half-life remain a serious challenge which should be addressed in future.