Lipid based nanocarriers: Production techniques, concepts, and commercialization aspect

Over the past decade, compared to all other macromolecules lipid-based nanocarriers have proven to be an excellent carrier and delivery system for various pharmaceutical drugs of poor bioavailability. In addition to that, they exhibit exceptional qualities such as minimal toxicity, economical scale-up production, great biocompatibility, and high drug loading efficiency. In this study, we have discussed the various types of lipid nanoparticles, such as liposomes, nanostructured lipid carriers, solid lipid nanoparticles, and lipid polymer hybrid nanoparticles. We have also conferred in detail, the composition, shape and size, methods of preparation, advantages, and certain limitations associated with these lipid-based nanocarriers. Additionally, we have exclusively accounted for several examples of lipid-based nanomedicines that have either been approved and commercialized or are under the different phases of clinical trials. The current review overall focuses on the up-to-date research that has recently been published in view of developing lipid-based nanocarriers for various biological applications, including gene therapy, breast cancer therapy, and vaccine development.Copyright © 2022

Controlled release nanomedicine (CRNM) of aspirin using "biomimetic niosomal nanoparticles (BNNs)”for Covid-19 and cardiovascular treatment: DOE based optimization

Biomimetic strategies can be adopted to improve biopharmaceutical aspects. Subsequently, Biomimetic reconstitutable pegylated amphiphilic lipid nanocarriers have high translational potential for systemic controlled drug delivery;however, such an improvised system for systemic aspirin delivery exploring nanotechnology is not available. Systemic administration of aspirin and its controlled delivery can significantly control blood clotting events, leading to stroke, which has immediate applications in cardiovascular diseases and Covid-19. In this work, we are developing aspirin sustained release pegylated amphiphilic self-assembling nanoparticles to develop reconstitutable aspirin injections by solvent-based co-precipitation method with phase inversion technique that leads to novel "biomimetic niosomal nanoparticles (BNNs).” DOE led optimization is done to develop Design of space for optimized particles. Upon reconstitution of solid powder, the particle size was 144.8 ± 12.90 nm with a surface charge of -29.2 ± 2.24 mV. The entrapment efficiency was found to be 49 ± 0.15%, wherein 96.99 ± 1.57% of the drug was released in 24hr showing super case II transport-based drug release mechanism. The formulation has the least hemolysis while showing significant suppression of platelet aggregation. MTT assay does not show any significant cytotoxicity. This is a potential nanoparticle that can be explored for developing aspirin injection, which is not available.

Controlled Release- Nanomedicine(CRNM) of aspirin using "Biomimetic Niosomal Nanoparticles (BNNs)”for Covid-19 and cardiovascular treatment: DOE based optimization

Biomimetic strategies can be adopted to improve biopharmaceutical aspects. Subsequently, Biomimetic reconstitutable pegylated amphiphilic lipid nanocarriers have high translation potential for systemic controlled drug delivery;however, such an improvised system for systemic aspirin delivery exploring nanotechnology is not available. Systemic administration of aspirin and its controlled delivery can significantly control blood clotting events, leading to stroke, which has applications in cardiovascular diseases and Covid-19. In this work, we are developing aspirin sustained release pegylated amphiphilic self-assembling nanoparticles to develop reconstitutable aspirin injections by solvent-based co-precipitation method with phase inversion technique that leads to novel "biomimetic niosomal nanoparticles (BNNs).” DOE led optimization is done to develop Design of space for optimized particles. Upon reconstitution of solid powder, the particle size was 144.8 ± 12.90 nm with a surface charge of -29.2 ± 2.24mV. The entrapment efficiency was found to be 49 ± 0.15%, wherein 96.99 ± 1.57 % of the drug was released in 24hr showing super case II transport-based drug release mechanism. The formulation has the least hemolysis while showing significant suppression of platelet aggregation. MTT assay does not show any significant cytotoxicity. This is a potential nanoparticle that can be explored for developing aspirin injection, which is not available.

Amikacin-loaded niosome nanoparticles improve amikacin activity against antibiotic-resistant Klebsiella pneumoniae strains.

Amikacin is an aminoglycoside antibiotic used in drug-resistant bacterial infections. The spread of bacterial infections has become a severe concern for the treatment system because of the simultaneous drug resistance bacteria and SARS-CoV-2 hospitalized patients. One of the most common bacteria in the development of drug resistance is Klebsiella strains, which is a severe threat due to the possibility of biofilm production. In this regard, recent nanotechnology studies have proposed using nanocarriers as a practical proposal to improve the performance of antibiotics and combat drug resistance. Among drug nanocarriers, niosomes are considered for their absorption mechanism, drug coverage, and biocompatibility. In this study, niosomal formulations were synthesized by the thin-layer method. After optimizing the synthesized niosomes, their properties were evaluated in terms of stability and drug release rate. The toxicity of the optimal formulation was then analyzed. The effect of free amikacin and amikacin encapsulated in niosome on biofilm inhibition were compared in multi-drug resistant isolated Klebsiella strains, and the mrkD gene expression was calculated. The MIC and MBC were measured for the free drug and amikacin loaded in the noisome. The particle size of synthesized amikacin-loaded niosomes ranged from 175.2 to 248.3 nm. The results showed that the amount of lipid and the molar ratio of tween 60 to span 60 has a positive effect on particle size, while the molar ratio of surfactant to cholesterol has a negative effect. The highest release rate in amikacin-loaded niosomes is visible in the first 8 h, and then a slower release occurs up to 72 h. The cytotoxicity induced by amikacin-loaded niosome is significantly less than the cytotoxicity of free amikacin in HFF cells (***p < 0.001, **p < 0.01). The mrkD mRNA expression level in the studied strains was significantly reduced after treatment with niosome-containing amikacin compared to free amikacin (***p < 0.001). It was confirmed that in the presence of the niosome, the amikacin antibacterial activity increased while the concentration of the drug used decreased, the formation of biofilm inhibited, and reduced antibiotics resistance in MDR Klebsiella strains.

Enhancement of Anti-Inflammatory Activity of Optimized Niosomal Colchicine Loaded into Jojoba Oil-Based Emulgel Using Response Surface Methodology.

Recent progression in investigational studies aiming to integrate natural products and plant oils in developing new dosage forms that would provide optimal therapeutic effect. Therefore, the aim of the present exploration was to inspect the influence of jojoba oil in boosting the anti-inflammatory effect of colchicine natural product. To our knowledge, there is no formulation comprising colchicine and jojoba oil together to form a niosomal emulgel preparation anticipated for topical application. Colchicine is a natural product extracted from Colchicum autumnale that has been evidenced to show respectable anti-inflammatory activity. Owing to its drawbacks and low therapeutic index, it was preferable to be formulated into topical dosage form. The current study inspected colchicine transdermal delivery by developing niosomal preparation as a potential nanocarrier included into emulgel prepared with jojoba oil. Box Behnken design was constructed to develop 17 niosomal emulgel formulations. The optimized colchicine niosomal emulgel was evaluated for its physical characteristics and in vitro release studies. The in vivo anti-inflammatory activity was estimated via carrageenan-induced rat hind paw edema method. The developed colchicine niosomal preparation revealed particle size of 220.7 nm with PDI value 0.22, entrapment efficiency 65.3%. The formulation was found to be stable showing no significant difference in particle size and entrapment efficiency up on storage at 4 °C and 25 °C for 3 months. The optimized colchicine niosomal emulgel exhibited a pH value 6.73, viscosity 4598 cP, and spreadability 38.3 mm. In vitro release study of colchicine from niosomal emulgel formulation was around 52.4% over 6 h. Apparently, the proficient anti-inflammatory activity of colchicine niosomal emulgel was confirmed via carrageenan-induced rat hind paw edema test. Overall, the results recommend the combination of niosomal preparation with jojoba oil-based emulgel that might signify a favorable delivery of anti-inflammatory drug such as colchicine.

Mesenchymal Stem Cells as a Gene Delivery Tool: Promise, Problems, and Prospects.

The cell-based approach in gene therapy arises as a promising strategy to provide safe, targeted, and efficient gene delivery. Owing to their unique features, as homing and tumor-tropism, mesenchymal stem cells (MSCs) have recently been introduced as an encouraging vehicle in gene therapy. Nevertheless, non-viral transfer of nucleic acids into MSCs remains limited due to various factors related to the main stakeholders of the process (e.g., nucleic acids, carriers, or cells). In this review, we have summarized the main types of nucleic acids used to transfect MSCs, the pros and cons, and applications of each. Then, we have emphasized on the most efficient lipid-based carriers for nucleic acids to MSCs, their main features, and some of their applications. While a myriad of studies have demonstrated the therapeutic potential for engineered MSCs therapy in various illnesses, optimization for clinical use is an ongoing challenge. On the way of improvement, genetically modified MSCs have been combined with various novel techniques and tools (e.g., exosomes, spheroids, 3D-Bioprinting, etc.,) aiming for more efficient and safe applications in biomedicine.