Lipid Nanocarriers Research Articles

Improved topical delivery of curcumin by hydrogels formed by composite carriers integrated with cyclodextrin metal-organic frameworks and cyclodextrin nanosponges

Curcumin (CUR) is highly promising for topical therapeutic applications, but water-insolubility is one of the major challenges plaguing its drugability, while conventional lipid nanocarriers are limited by low drug-carrying capacity, many additives, and complex processes. In the current work, we constructed a composite carrier integrated with cyclodextrin metal-organic framework (γ-CD-MOF) and cyclodextrin nanosponge (β-CDNS), in which the γ-CD-MOF had 13.9 % drug loading and 267.1-fold increase in solubility in water for CUR, and the β-CDNS showed bioadhesion and further increasing drug solubility. The composite carrier (γ-CD-MOF@β-CDNS) significantly improved the in vitro release and transdermal permeation of CUR, and its limited water absorption properties and excellent bioadhesion create an advantage in the local administration of the drug for treating diseases with high exudate, which prevents the affected area from deteriorating the condition by counter-absorption of water from the formulation. Thus, this composite carrier contributes a new option to address the local delivery of insoluble drugs and offers a promising strategy for the clinical application of CUR.

Lipid nanocarrier-based bigel of Piper betel oil for analgesic and anti-inflammatory applications

Present study reports analgesic and anti-inflammatory potential of Piper betel (L.) leaf oil loaded lipid nanocarrier (BLNs)-embedded bigel. BLNs were developed by solvent evaporation technique and were characterised by FESEM, Cryo-TEM, mean diameter, zeta potential, loading efficiency, etc. BLNs embedded bigel (BLNs-G) was evaluated for analgesic and anti-inflammatory efficacy in rat model. Data showed spherical BLNs with intact lamellarity, 138.2 ± 1.08 nm mean diameter, 0.182 PDI, −46.6 ± 0.61 mV zeta potential, 76.2 ± 2.1% (w/w) loading efficiency and a sustained release in vitro. BLNs-G was homogenous with satisfied viscosity (40 734 ± 1.7 cps), spreadability (8.3 ± 1.5 g.cm sec−1), extrudability (91.33 ± 1.3% w/w) along with a sustained permeation ex vivo. Significant analgesic and anti-inflammatory action were depicted by BLNs-G (1% w/w) in rat model (p ˂ 0.05) within 30 minutes post topical application. In silico docking study revealed high affinity of major phytoactive components with key analgesic/inflammatory mediators. Further pre-clinical investigations are warranted for futuristic clinical application of BLNs-G.

Charge-Stabilized Nanodiscs as a New Class of Lipid Nanoparticles.

Nanoparticles have the potential to improve disease treatment and diagnosis due to their ability to incorporate drugs, alter pharmacokinetics, and enable tissue targeting. While considerable effort is placed on developing spherical lipid-based nanocarriers, recent evidence suggests that high aspect ratio lipid nanocarriers can exhibit enhanced disease site targeting and altered cellular interactions. However, the assembly of lipid-based nanoparticles into non-spherical morphologies has typically required incorporating additional agents such as synthetic polymers, proteins, lipid-polymer conjugates, or detergents. Here, charged lipid headgroups are used to generate stable discoidal lipid nanoparticles from mixed micelles, which are termed charge-stabilized nanodiscs (CNDs). The ability to generate CNDs in buffers with physiological ionic strength is restricted to lipids with more than one anionic group, whereas monovalent lipids only generate small nanoliposomal assemblies. In mice, the smaller size and anisotropic shape of CNDs promote higher accumulation in subcutaneous tumors than spherical liposomes. Further, the surface chemistry of CNDs can be modified via layer-by-layer (LbL) assembly to improve their tumor-targeting properties over state-of-the-art LbL-liposomes when tested using a metastatic model of ovarian cancer. The application of charge-mediated anisotropy in lipid-based assemblies can aid in the future design of biomaterials and cell-membrane mimetic structures.

In vitro evaluation of lipidic nanocarriers for mebendazole delivery to improve anticancer activity

Objective To enhance the anticancer activity of the repurposed drug mebendazole (MBZ) against A549 cell lines by developing nanostructured lipid carriers (NLCs). Significance MBZ, an anthelmintic drug, exhibits anticancer properties primarily through the inhibition of Ran GTPase and mitotic spindle assembly. Enhancing its delivery and efficacy via NLC could provide a novel and effective approach for lung cancer treatment. Methods NLCs were prepared by mixing different ratios of solid lipid (stearic acid) and liquid lipid (oleic acid) with surfactants and emulsifiers. The NLCs were fully characterized to ensure stability, particle size, zeta potential, and encapsulation efficiency (EE%). The stability of the NLCs was monitored over a 3-week period. The anticancer activity of MBZ-NLCs was evaluated using IC50 assays and in vitro scratch assays. Results The NLCs exhibited an average particle size of 300 ± 10 nm and a zeta potential of −27 ± 0.5 mV, indicating good stability. EE% significantly improved from 40% in conventional liposome formulations to 90.7% in NLCs. The anticancer activity of MBZ-NLCs was markedly enhanced, with an IC50 of 62 nM compared to 581 nM for free MBZ, representing a 10-fold increase in potency. Additionally, in vitro scratch assays revealed that MBZ-NLCs effectively prevented cell–cell contact, further supporting their potential for improved therapeutic efficacy. Conclusion MBZ-NLCs exhibit significantly improved stability, EE%, and anticancer activity compared to free MBZ. These promising results suggest that MBZ-NLCs could be a potent therapeutic approach for lung cancer treatment, warranting further in vivo studies and exploration of different administration routes.

Nanotechnological prospective for enhancing the antibacterial activity of mupirocin and cinnamon essential oil: a combination therapy.

The aim of the current study was to develop a distinctive nanolipid formulation, namely, nanostructured lipid carrier (NLC), which would deliver an antibacterial medication such as mupirocin (MP). Additionally, cinnamon essential oil (CEO), which is reported to exhibit antibacterial activity, was utilized in the development process in an attempt to improve the influence of MP. As a consequence, different MP-NLC formulations were developed using the central composite design (CCD) approach. One optimized formula was selected and incorporated within the pre-formulated gel matrix, providing the MP-NLC-gel formula for efficient topical application. MP-NLC-gel was assessed for its physical characteristics to check its suitability for topical application and evaluated for its in vitro drug release over 6h. Furthermore, it studied the formulation for its stability at different conditions; 25°C ± 2°C and at 4°C ± 3°C for 6 months. Finally, the formulation was examined for its antibacterial performance against gram-positive and -negative bacteria. The developed topical NLC-gel formulation demonstrated pH 5.8, viscosity 14,510cP, and spreadability 58.1mm, which were seemed to be satisfactory properties for successful topical application. The drug was released successfully for over 6h with 52.9%. Additionally, it was stable in both storage conditions for 6months since it displayed non-significant variations in its evaluated characteristics compared to those of fresh preparation. Ultimately, the developed gel formulation could inhibit the growth of different bacterial strains, especially gram-negative strains. To sum up, these findings would demonstrate the efficiency of NLC prepared with CEO and incorporating MP to be a promising antibacterial lipid nanocarrier.

The utilization of Rutin-loaded lipid nanoparticles as promise carriers to enhance the therapeutic efficacy in ovarian cancer: A computational and experimental study

Since natural chemicals can act as multi-targeted agents in the fight against cancer, recently, highly interested in using them to reduce the adverse effects of cancer treatment, therefore, developing novel and efficient therapeutic methods for cancer is paramount. Studies have demonstrated that Ru exhibits widespread pharmacological properties, such as antioxidant, anti-inflammatory, antiangiogenic, pro-apoptotic, and anti-proliferative activities. These qualities can potentially contribute to the prevention and treatment of cancer. This research aims to develop nano-lipid carriers (NLC) that transport the Ru to OV (SK-OV-3), forcing them to undergo apoptosis and ultimately terminate the cancer cell’s life. First, the molecular structure of water, and other materials were constructed using Material Studio software. Then, the structure of the molecules was optimized through the Forcite module in the software. In sequence, to set the temperature of the system the MD simulations were run under the NVT ensemble with velocity scale as a thermostat and total simulation time equal to 100 ps as the initialization step. We applied the hydrophobic-hydrophobic interactions and micellization process method to encapsulate Ru into NLC. The computational studies showed that in the first 30 ps of the simulation, the system was unstable, but after that, the system reached a stable condition. Moreover, we observed that the density of the system rapidly decreased to a stable mean value equal. Also, the characterizations using DLS and TEM imaging showed that the synthesized NPs have a size lower than 100 nm. The hemolysis evaluation showed that the Ru-micelles are hemocompatible and induced lower than 10 % hemolysis in all tested group. The result shows that the synthesized NLC loading efficiency was 73.63 %, and the particle size was 76 ± 3 nm. The Ru release experiment demonstrated that the loaded sample (Ru-NLC) exhibited a steady release effect, with a total release amount of 84.62 ± 1.61 % of the loaded quantity over 48 h. The findings of in vitro results indicate that Ru-NLC substantially impacts the metabolism of SK-OV-3 cells, and ultimately increases the amount of apoptosis protein levels. Because of these alterations, the cell’s capacity for growth is diminished, and it ultimately dies due to intrinsic apoptosis. The results of the Western blotting experiment indicate that Ru-NLC increases the apoptosis in cancer cells. At long last, we have demonstrated that loading Ru into NLC increased the solubility and bioavailability and could increase the therapeutic efficacy.

Liposomes and Their Therapeutic Applications in Enhancing Psoriasis and Breast Cancer Treatments.

Psoriasis and breast cancer are two examples of diseases where associated inflammatory pathways within the body's immune system are implicated. Psoriasis is a complex, chronic and incurable inflammatory skin disorder that is primarily recognized by thick, scaly plaques on the skin. The most noticeable pathophysiological effect of psoriasis is the abnormal proliferation of keratinocytes. Breast cancer is currently the most diagnosed cancer and the leading cause of cancer-related death among women globally. While treatments targeting the primary tumor have significantly improved, preventing metastasis with systemic treatments is less effective. Nanocarriers such as liposomes and lipid nanoparticles have emerged as promising drug delivery systems for drug targeting and specificity. Advances in technologies and drug combinations have emerged to develop more efficient lipid nanocarriers to include more than one drug in combinational therapy to enhance treatment outcomes and/or relief symptoms for better patients' quality of life. Although there are FDA-approved liposomes with anti-cancer drugs for breast cancer, there are still unmet clinical needs to reduce the side effects associated with those nanomedicines. Hence, combinational nano-therapy may eliminate some of the issues and challenges. Furthermore, there are no nanomedicines yet clinically available for psoriasis. Hence, this review will focus on liposomes encapsulated single and/or combinational therapy to augment treatment outcomes with an emphasis on the effectiveness of combinational therapy within liposomal-based nanoparticulate drug delivery systems to tackle psoriasis and breast cancer. This review will also include an overview of both diseases, challenges in delivering drug therapy and the roles of nanomedicines as well as psoriasis and breast cancer models used for testing therapeutic interventions to pave the way for effective in vivo testing prior to the clinical trials.

Nanomaterial-Enhanced Microneedles: Emerging Therapies for Diabetes and Obesity.

Drug delivery systems (DDS) have improved therapeutic agent administration by enhancing efficacy and patient compliance while minimizing side effects. They enable targeted delivery, controlled release, and improved bioavailability. Transdermal drug delivery systems (TDDS) offer non-invasive medication administration and have evolved to include methods such as chemical enhancers, iontophoresis, microneedles (MN), and nanocarriers. MN technology provides innovative solutions for chronic metabolic diseases like diabetes and obesity using various MN types. For diabetes management, MNs enable continuous glucose monitoring, diabetic wound healing, and painless insulin delivery. For obesity treatment, MNs provide sustained transdermal delivery of anti-obesity drugs or nanoparticles (NPs). Hybrid systems integrating wearable sensors and smart materials enhance treatment effectiveness and patient management. Nanotechnology has advanced drug delivery by integrating nano-scaled materials like liposomes and polymeric NPs with MNs. In diabetes management, glucose-responsive NPs facilitate smart insulin delivery. At the same time, lipid nanocarriers in dissolving MNs enable extended release for obesity treatment, enhancing drug stability and absorption for improved metabolic disorder therapies. DDS for obesity and diabetes are advancing toward personalized treatments using smart MN enhanced with nanomaterials. These innovative approaches can enhance patient outcomes through precise drug administration and real-time monitoring. However, widespread implementation faces challenges in ensuring biocompatibility, improving technologies, scaling production, and obtaining regulatory approval. This review will present recent advances in developing and applying nanomaterial-enhanced MNs for diabetes and obesity management while also discussing the challenges, limitations, and future perspectives of these innovative DDS.

Nanostructured Lipid Carrier-based Topical Gels as Novel Drug Delivery System: A Comprehensive Overview.

Nanostructured lipid carriers (NLCs) are lipidic nanocarriers that recover the permanency and capacity of drug payloads. NLCs are well-known as second-generation lipid nanocarriers with an unstructured matrix, presenting potentially advantageous nanocarrier systems with marketable opportunities because of reproducible production methodologies and biocompatible lipidic excipients. These (NLCs) are now recognized as a very promising nanocarrier structure for the efficient delivery of drugs via different administration routes. In recent years, several NLC-based gels have been developed and evaluated for topical delivery of many drugs and other therapeutic agents. This review article presents an overview of NLC-based topical gels investigated to deliver drugs via ocular, dermal, and transdermal routes. In addition, the classification, manufacturing, characterizations, advantages, and disadvantages of NLCs are addressed in this article. We also discussed different evaluations of NLC-based topical gels.

Effects of thermal processing and pH on the physicochemical properties, stability, and structure of taxifolin-loaded nanostructured lipid carriers

In the present study the potential of nanolipid carriers (transfersomes) for improving the oral delivery of taxifolin, a poorly water-soluble bioactive compound with high antioxidant and anti-inflammatory activity was evaluated. Two transfersome formulations were prepared using lecithin, Span®60, and Tween®80, with cholesterol as a stabilizer (FA) and without cholesterol (FB), by the Ethanol Injection Method (EIM). The influences of thermal treatment (60–90 °C) and pH (2, 4, 6, and 8) on physical stability, structure, and taxifolin degradation were evaluated. The transfersomes were physically and chemically stable during heating at lower temperatures (≤70 °C), while thermal treatment at 80–90 °C led to an increase in particle size (an increase of around 200 nm) and a decrease in taxifolin encapsulation. Moreover, there was no significant difference in particle size or polydispersity index (PDI) at high temperatures. The particle sizes of transfersomes FA and FB increased from 128 to 182 nm at pH 7 to 224 and 331 nm at pH 2, respectively. Both transfersome preparations remained relatively stable, with consistent antioxidant activity (IC50 = 0.64 mg ml−1) over four weeks of storage at different temperatures (4, 25, and 40 °C), showing higher stability at lower temperatures. The in vitro digestion experiment indicated physical stability after exposure to the simulated stomach stage. However, the reduction in the nanovesicles' surface charge after incubation with gastric juice, increased particle size. Based on these results, taxifolin-loaded transfersomes can be pasteurized at low temperatures, for incorporation into enriched food and beverage products.

Colloidal Structure Dictates Antimicrobial Efficacy in LL-37 Self-Assemblies With Glycerol Monooleate.

The antimicrobial peptide LL-37 is a promising alternative to conventional antibiotics to combat bacteria in suspension and biofilms. Its self-assembly with polar lipids is suggested to improve its potential for therapeutic applications with higher stability against degradation and bioavailability. This study investigates the self-assembly of LL-37 with glyceryl monooleate (GMO), establishing the link between colloidal structure and antimicrobial activity. Small-angle X-ray scattering, dynamic light scattering and cryogenic transmission electron microscopy show structural transformation from dispersions of inverse bicontinuous structure (cubosomes) to multilamellar vesicles and direct rod-like mixed-micelles upon increasing the content of LL-37 in GMO. In vitro assays against planktonic and biofilm cells demonstrate that 128 µg mL-1 of GMO cubosomes have no impact on Pseudomonas aeruginosa. Still, the cubosomes reduce the Staphylococcus aureus planktonic population by ≈ 1-log after 24 h. Cylindrical micelles formed at LL-37/GMO 9/1 and 8/2 with 128 µg mL-1 LL-37 decrease the Pseudomonas aeruginosa population by 6-log. This activity is gradually abolished when LL-37 is encapsulated in vesicles or cubosomes. They also demonstrate low antibiofilm efficacy and promote the biomass of Staphylococcus aureus biofilms. These results highlight the importance of colloidal structure for therapeutic outcomes, providing insights for advanced lipid nanocarrier designs.

Guiding Therapeutics: Lipid Labyrinths and Nanostructures for Enhanced Drug Delivery

Abstract: Nanostructured lipid carriers (NLCs) offer a breakthrough platform for drug therapy, surpassing traditional limitations and delivering exceptional performance. Among various nanoparticulate systems, lipid nanoparticles stand out as one of the most promising options for medication delivery. NLCs stand out due to their solid matrix at ambient temperatures, setting them apart from conventional lipid-based carriers such as nanoemulsions and solid lipid nanoparticles. This paper thoroughly explores the makeup, classification, components, and various methods of preparing NLCs, based on extensive research findings. It emphasizes their numerous advantages, such as improved stability, minimal toxicity, extended storage capability, increased drug-loading capacity, and compatibility with biological systems. The review provides insights into the advantages and limitations of each method. Exploring the intricacies of drug loading and release, the review also addresses strategies to bolster NLCs’ stability. Moreover, it provides a detailed summary of both laboratory- based and animal studies demonstrating the efficacy of NLCs carrying cytotoxic drugs, particularly emphasizing their promise in targeted drug delivery to the brain. As the next-generation lipid nanocarriers, NLCs are composed of physiological and biocompatible lipids, rendering them novel pharmaceutical formulations. These colloidal drug delivery systems boast a solid lipid matrix with nanosized structures, offering superior drug loading capacity, physical stability, and bioavailability compared to conventional lipid nanoparticles. Several techniques, including high-pressure homogenization, microemulsion, solvent evaporation, and melt emulsification, add to the flexibility of nanostructured lipid carriers. Additionally, their exterior can be altered using coatings such as polyethylene glycol, chitosan, or antibodies to improve targeting ability and stealth characteristics. By elucidating the promising role of NLCs across diverse drug delivery systems, this review stimulates interest in their potential applications. It underscores the significance of understanding the structure, content, multiple formulation procedures, and characterization of NLCs, which are pivotal aspects for establishing stable drug delivery systems.

Age-Related Macular Degeneration (AMD): Pathophysiology, Drug Targeting Approaches, and Recent Developments in Nanotherapeutics

The most prevalent reason for vision impairment in aging inhabitants is age-related macular degeneration (AMD), a posterior ocular disease with a poor understanding of the anatomic, genetic, and pathophysiological progression of the disease. Recently, new insights exploring the role of atrophic changes in the retinal pigment epithelium, extracellular drusen deposits, lysosomal lipofuscin, and various genes have been investigated in the progression of AMD. Hence, this review explores the incidence and risk factors for AMD, such as oxidative stress, inflammation, the complement system, and the involvement of bioactive lipids and their role in angiogenesis. In addition to intravitreal anti-vascular endothelial growth factor (VEGF) therapy and other therapeutic interventions such as oral kinase inhibitors, photodynamic, gene, and antioxidant therapy, as well as their benefits and drawbacks as AMD treatment options, strategic drug delivery methods, including drug delivery routes with a focus on intravitreal pharmacokinetics, are investigated. Further, the recent advancements in nanoformulations such as polymeric and lipid nanocarriers, liposomes, etc., intended for ocular drug delivery with pros and cons are too summarized. Therefore, the purpose of this review is to give new researchers an understanding of AMD pathophysiology, with an emphasis on angiogenesis, inflammation, the function of bioactive lipids, and therapy options. Additionally, drug delivery options that focus on the development of drug delivery system(s) via several routes of delivery can aid in the advancement of therapeutic choices.

Metal Complexation for the Rational Design of Gemcitabine Formulations in Cancer Therapy.

Nanoformulation of chemotherapies represents a promising strategy to enhance outcomes in cancer therapy. Gemcitabine is a chemotherapeutic agent approved by the Food and Drug Administration for the treatment of various solid tumors. Nevertheless, its therapeutic effectiveness is constrained by its poor metabolic stability and pharmacokinetic profile. Nanoformulations of gemcitabine in lipid and polymer nanocarriers usually lead to poor loading capability and an inability to effectively control its release profile due to the physicochemical characteristics of the drug and matrices. Here, we propose metal-gemcitabine complexation with biorelevant metal cations as a strategy to alter the properties of gemcitabine in a noncovalent manner, paving the way for the development of novel nanoformulations. A speciation study on gemcitabine and Mn2+, Zn2+, and Ca2+ was performed with the aim of investigating the extent of the interaction between the drug and the proposed metal cations, and selecting the best conditions of temperature, pH, and drug-to-metal molar ratio that optimize such interactions. Also, a series of density functional theory calculations and spin-polarized ab initio molecular dynamics simulations were carried out to achieve insights on the atomistic modalities of these interactions. Mn2+-gemcitabine species demonstrated the ability to maintain gemcitabine's biological activity in vitro. The scientific relevance of this study lies in its potential to propose metal-gemcitabine as a valuable strategy for developing nanoformulations with optimized quality target product profiles. The work is also clinically relevant because it will lead to improved treatment outcomes, including enhanced efficacy and pharmacokinetics, decreased toxicity, and new clinical possibilities for this potent therapeutic molecule.

Exploring Applications of Flexible Vesicular Systems as Transdermal Drug Delivery.

Deformable lipidic-nano carriers are a category of advanced liposomal formulations. Deformable lipidic-nano carriers have a specific character to transform by rearranging the lipidic backbone to squeeze themself through a pore opening ten times smaller than their diameter when exposed to a variable condition like hydration gradient as these have potentially been used as a non-invasive delivery system to transdermally migrate various therapeutic agents for over three decades. Despite their vast application in transdermal drug delivery system, non-uniformity to express their chemical nature still exist and authors use various terms synonymously and interchangeably with each other. The present study delineates the terminologies used to express different derived deformable vesicular carriers to harmonize the terminological use. It also includes the effectiveness of deformable nanocarriers like Transferosomes, Ethosomes, Menthosomes, Invasomes, and Glycerosomes in skin conditions like basal cell carcinoma, fungal and viral infections, and hyperpigmentation disorders, along with others. Various review and research articles were selected from the 'Pubmed' database. The keywords like Transferosomes, Flexi-vesicular system, ultra-deformable vesicles, and nano-vesicular systems were used to extract the data. The data was reviewed and compiled to categorically classify different flexible vesicular systems. The composition of the different vesicular systems is identified and a report of various pathological conditions where the use of flexible lipid nanocarrier systems was implemented is compiled. The review also offers suggestive approaches where the applicability of these systems can be explored further.

Hyaluronic acid-decorated lipid nanocarriers as novel vehicles for curcumin: Improved stability, cellular absorption, and anti-inflammatory effects

This study aimed to investigate how hyaluronic acid interfacial decoration affects the stability, cellular absorption, and anti-inflammatory effects of curcumin-loaded nanostructured lipid carriers. Nanocarriers were synthesized with an ovalbumin single layer and ovalbumin/hyaluronic acid double, mixed, or conjugated layers. All nanocarriers were spherical (200–300 nm diameter), and their encapsulation efficiency exceeded 95 %. Among the layers, the conjugated one exhibited the highest elastic surface dilatational modulus of approximately 40 mN/m, and the longest curcumin half-life of 186.07 days at 4 °C. Spearman's correlation analysis showed a negative correlation (r = −0.6698) between the recrystallization index and curcumin stability. The layer's mechanical strength improved curcumin stability by preventing crystal transition. Hyaluronic acid decoration enhanced the curcumin uptake of Caco-2 cells by 1.96–2.48 folds. Among the layers, the conjugate one was the most effective because of its strong binding constant with the receptor. Hyaluronic acid decoration improved the anti-inflammatory effects of curcumin.

Formulation and Evaluation of Nano-particles Loaded with Salvia miltiorriza by Homogenization Method

Aims: The aim of the present study is to formulate and evaluate the Salvia miltorrhizaloaded Nano-structured lipid carriers(SM-NLC) in order to enhance the aqueous solubility and bioavailability as the efficacy of Salvia miltiorriza extract has been restricted due to less solubility and low bioavailability. Introduction: Salvia miltiorrhiza is a well-known Chinese herb that belongs to the family Labiatae. The herb has been widely used to treat various kinds of ailments, and its main phytochemical constituents are Tanshinone I, Tanshinone II, Miltirone, and Salvionolic acid, which are mainly found in the extract of roots. These Phytochemical constituents are responsible for several pharmacological activities such as anti-oxidant, anti-microbial, anti-hyperlipidemic, anti-inflammatory, cardiovascular diseases etc. Objective: Nano-lipid carriers are useful in enhancing the solubility of poor water-soluble drugs. The faulty lattice arrangement of Nano-lipid carriers (NLC) provides better entrapment, thus providing more space for the drug to incorporate in the lattice structure of NLC, improving the stability of the formulation and preventing the drug leakage from the matrix. Methods: SM-NLCs were prepared by using oleic acid and stearic acid as liquid and solid lipids, respectively and tween 80 as the surfactant by high-speed homogenization method. The optimization of SM- NLC was performed by applying the Box-Behnken experimental design. The independent variables were chosen as the amount of lipids, surfactant concentration, and sonication time, whereas dependent variables were opted as particle size and entrapment efficiency. The influence of different proportions of the lipids (Stearic acid and Oleic acid) and the surfactant (Tween 80) was analysed on the dependent variables. The optimized formulation was evaluated for Particle size (241.7nm±3), Polydispersity index (.249 ±0.05), Zeta Potential (-14.6±5), and entrapment efficiency (82.49%). Scanning Electron Microscopy (SEM) was performed to identify the surface morphology, and the entrapment of the drug into the nanostructured matrix was verified by Differential Scanning Calorimetry. The interaction between the formulations was confirmed by performing FTIR. The dialysis bag method was performed to calculate the in vitro drug release from the optimized formulation. Additionally, a stability study was performed for 1 month of duration. Result: The SM NLCs were successfully formulated based on the Box-Behnken design. Particle size, PDI, zeta potential, and EE demonstrated less than a 5% difference compared to the predicted value. The formulations did not show any possible interactions with the lipids. The optimized formulations were found stable after one month of stability studies. Conclusion: The above results confirmed that Salvia miltiorrhiza could be effectively formulated in the form of a nanostructured-lipid carrier system. The formulation and evaluation of nanoparticles have been performed successfully using the homogenization method.

Retinol and Oligopeptide-Loaded Lipid Nanocarriers as Effective Raw Material in Anti-Acne and Anti-Aging Therapies

The use of lipid nanocarriers as components of cosmetic formulations may provide an opportunity to fully exploit the beneficial properties of pentapeptide-18 and retinol while reducing the undesirable effects that occur during retinoid therapy. This study aimed to evaluate the effectiveness of semi-solid formulations enriched with retinol and oligopeptide-loaded lipid nanocarriers. Solid lipid nanoparticles were produced using a high-shear homogenization method. The work included physicochemical characterization of the cosmetic products, and evaluation of their stability as well as their efficacy. The resulting semi-solid preparations were determined to be stable regardless of their storage temperature. No effect of the presence of lipid nanoparticles on the shelf-life stability of the cosmetic products was observed. A temperature of 25 °C was considered the recommended storage temperature for the tested semi-solid formulations. Beneficial effects of the cosmetic products were proven (in vivo study on volunteers), i.e., a significant reduction in the level of sebum secretion (anti-acne therapy) and a decrease in the number of facial wrinkles (anti-aging therapy). In addition, the protective properties of the lipid nanoparticles themselves against the skin were confirmed, reducing the irritating effect of retinol that is usually the case with classic retinoid therapies.

Lipid-based Non-viral Vector: Promising Approach for Gene Delivery.

The present review aims to discuss various strategies to overcome intracellular and extracellular barriers involved in gene delivery as well as the advantages, challenges, and mechanisms of gene delivery using non-viral vectors. Additionally, patents, clinical studies, and various formulation approaches related to lipid-based carrier systems are discussed. Data were searched and collected from Google Scholar, ScienceDirect, Pubmed, and Springer. In this review, we have investigated the advantages of non-viral vectors over viral vectors. The advantage of using non-viral vectors are that they seek more attention in different fields. They play an important role in delivering the genetic materials. However, few nonviral vector-based carrier systems have been found in clinical settings. Challenges are developing more stable, site-specific gene delivery and conducting thorough safety assessments to minimize the undesired effects. In comparison to viral vectors, nonviral vector-based lipid nanocarriers have more advantages for gene delivery. Gene therapy research shows promise in addressing health concerns. Lipid-based nanocarriers can overcome intracellular and extracellular barriers, allowing efficient delivery of genetic materials. Non-viral vectors are more attractive due to their biocompatibility, ease of synthesis, and cost-effectiveness. They can deliver various nucleic acids and have improved gene delivery efficacy by avoiding degradation steps. Despite limited clinical use, many patents have been filed for mRNA vaccine delivery using non-viral vectors.

Nebulized, macrophage-targeted, Linezolid-loaded lipid carriers for intracellular treatment of tubercular infections – In vitro/in vivo study

Effective treatment of tuberculosis (TB) demands progression control in line with TB elimination. The objective herein is to formulate nebulized targeted antitubercular - lipid nanocarriers for TB treatment. In this context, mannosylated solid lipid nanoparticles (MN-SLNs) incorporating LNZ (LNZ) were prepared and characterized. Their nebulization efficiency and cytotoxicity were appraised. Potential internalization of LNZ-MN-SLNs in alveolar macrophages (AM) was evaluated. In vivo biodistribution was carried out following orotracheal administration to mice. Susceptibility testing to investigate antitubercular activity of LNZ formulations against Mycobacterium tuberculosis (standard strain and clinical isolates) was performed.MN-SLNs ensured ≈930 nm diameter, 5–54 mV zeta-potential and 19 %w/v LNZ loading in addition to pH-independent sustained release. Jet nebulization showed 51 % nebulization efficiency within 20 min. Viability assay on MH-S cells warranted an IC50 < 0.02 mg/mL, while no harmful effect on A549 cells was noticed. CLSM has proven phagocytosis of labelled carriers by MH-S cells as revealed by the 4-time higher fluorescence for LNZ-MN-SLNs versus LNZ-MN-NLCs. Data support 50 % reduction in MIC for LNZ-MN-SLNs versus free LNZ against standard and clinical M. tuberculosis isolates. H&E staining and bronchoalveolar lavage demonstrated in vivo accumulation of mannosylated nanocarriers in murine AM without significant histopathological/biochemical changes emphasizing their notable biosafety. The formulated nebulization therapy showed in vitro/in vivo macrophage targeting, and privileged susceptibility against TB giving promises for reduced dose and dosing frequency, evading LNZ life-threatening adverse consequences.