Lipid-based Delivery Systems Research Articles

Computational approaches to lipid-based nucleic acid delivery systems

Nucleic acid-based therapies have shown enormous effectiveness as vaccines against the recent COVID19 pandemics and hold great promises in the fight of a broad spectrum of diseases ranging from viral infections to cancer up to genetically transmitted pathologies. Due to their highly degradable polyanionic nature, nucleic acids need to be packed in sophisticate delivery vehicles which compact them up, protect them from early degradation and help delivery them to the right tissue/cells. Lipid-based nanoparticles (LNP) represent, at present, the main solution for nucleic acid delivery. They are made of a mixture of lipids whose key ingredient is an ionizable cationic lipid. Indeed, the interactions between the polyanionic nucleic acids and the ionizable cationic lipids, and their pH-dependent regulation in the life cycle of the nanoparticle, from production to cargo delivery, mostly determine the effectiveness of the therapeutic approach. Notwithstanding the large improvements in the delivery efficiency of LNPs in the last two decades, it is estimated that only a small fraction of the cargo is actually delivered, stimulating further research for the design of more effective LNP formulations. A rationally driven design would profit from the knowledge of the precise molecular structure of these materials, which is however still either missing or characterized by poor spatial resolution. Computational approaches have often been used as a molecular microscope either to enrich the available experimental data and provide a molecular-level picture of the LNPs or even simulate specific processes involving the formation and/or the molecular mechanisms of action of the LNP. Here, I review the recent literature in the field.

Evaluation of extraction and entrapment efficiency of black seed oil-containing emulsion as a delivery system for thymoquinone

Black seed oil (BSO) or Nigella sativa contains numerous bioactive components, in which thymoquinone (TQ) becomes a functional key compound and serves as an analytical marker. With its non-polar characteristic, lipid-based delivery systems can be a solution to improve the solubility of BSO. Thus, it is necessary to have a valid basis for TQ quantification, especially in the emulsion as the delivery system of BSO. This study aimed to validate a Gas Chromatography-Flame Ionization Detector (GC-FID) method for quantifying TQ, and subsequently employ the method to evaluate TQ extraction from BSO and BSO-containing emulsion and determine the entrapment efficiency of the emulsion. The method indicated a linearity between 10 and 1280 µg/ml with detection and quantification limits of 13,59 and 41,19 µg/ml, respectively. The extraction of TQ with the sample:methanol ratio of 1:9 and 30-min centrifugation yielded the maximum TQ recovery from BSO and BSO-containing emulsion. The entrapment efficiency in emulsion reached 64,83% obtained with the density-changing centrifugation method. Overall, this validated GC-FID method demonstrated that the selected condition in the methanol extraction could effectively separate TQ from both BSO and its emulsion matrices and support the determination of the entrapment efficiency of the BSO-containing emulsion.

Evaluating human milk as a drug delivery vehicle for clofazimine to premature infants

Human milk is proposed as a drug delivery vehicle suitable for use in neonatal patients. Clofazimine, traditionally used for the treatment of leprosy and tuberculosis, is emerging as a treatment for cryptosporidiosis in infants, however its poor aqueous solubility has led to its commercial formulation as a waxy lipid formulation in a capsule, a format that is not suitable for infants. In this study, the evaluation of pasteurised human milk for the delivery of clofazimine was investigated using an in vitro lipolysis model to simulate gastric and intestinal digestion. The total lipid composition of the human milk was characterised alongside the liberated fatty acid species following digestion for comparison to alternative lipid-based delivery systems. Small-angle X-ray scattering was used to measure the presence of crystalline clofazimine during digestion and hence the extent of drug solubilisation. High-performance liquid chromatography was used to quantify the mass of clofazimine solubilised per gram of human milk fat (drug-to-fat ratio) in digested and undigested human milk. The digestion process was essential for the solubilisation of clofazimine, with digested human milk solubilising a sufficient dose of clofazimine for treatment of a premature infant. Human milk solubilised the clofazimine to a greater extent than bovine milk and infant formula during digestion, most likely as a result of differing lipid composition and increased long-chain fatty acid concentrations. These findings show that human milk enhances the solubility of clofazimine as a model drug and may be a suitable drug delivery vehicle for infant populations requiring therapeutic treatment.

Phytoconstituents Loaded Liposomes Fabricated Based on Box Behnken Design for Metabolic Syndrome: <i>In Vitro</i> and <i>In Vivo</i> Characterization

The global use of secondary metabolites like flavonoids, plant sterols, and alkaloids has been increasing due to their therapeutic benefits and fewer side effects compared to modern medicines. However, despite promising in vitro results, many herbal drugs and extracts demonstrate limited effectiveness in vivo due to their low lipid solubility and poor bioavailability. To address this issue, novel formulation strategies, particularly lipid-based delivery systems, are being proposed as carriers to enhance their bioavailability. This study focuses on the pharmaceutical development of liposomes that encapsulate three phytoconstituents, namely quercetin, berberine, and phytosterol, using the Quality by Design (QbD) concept. The Ishikawa diagram was utilized to identify the key factors affecting formulation quality, and the statistical experiment design concept was employed to optimize these factors. The liposomes were designed using the screening with the Placket-Burman approach and further optimized using the Box-Behnken method. The optimized liposomes exhibited an ideal size and achieved high entrapment efficiencies of 80.6%, 81.3%, and 80.35% for quercetin, berberine, and phytosterol, respectively. These liposomes were prepared using Phospholipon 90 G and cholesterol through the thin film hydration method. The resulting liposomes were thoroughly characterized and evaluated for morphology, % drug release, pharmacodynamic investigation, and stability studies.

A Comprehensive Literature Review of Lipids Used in the Formulation of Lipid Nanoparticles

Abstract: Lipid nanocarriers are reaching new heights in the field of drug delivery. The core of this technology resides in simple molecules, i.e., lipids. Solid and liquid lipids of biocompatible and generally recognized as safe (GRAS) status are employed for the development of lipid nanoparticles along with surfactant(s), solvents, and drug molecules. Researchers have practiced a variety of solid and liquid lipids with acceptable profiles in the formulation of lipid nanoparticles. Solid lipids like triglycerides, fatty acids, fatty alcohols, waxes, and butter have been used in designing lipid nanocarriers. The potential of various plant-based oils has also been tested in designing nanostructured lipid carriers (NLC). With the exponential advancement in lipid-based delivery systems, there exists a need for an appropriate lipid system to obtain an effective product. This review gives a brief insight into lipids, which have been exploited by researchers for designing solid lipid nanoparticles (SLN) and nanostructured lipid carriers. A tabular presentation of important key points of past studies exploiting these lipids for preparing SLN/NLC is the highlight of the article.

Synergistic Amplification of Ferroptosis with Liposomal Oxidation Catalyst and Gpx4 Inhibitor for Enhanced Cancer Therapy.

As a distinctly different way from apoptosis, ferroptosis can cause cell death through excessive accumulation of lipid peroxide (LPO) and show great potential for cancer therapy. However, efficient strategies for ferroptosis therapy are still facing great challenges, mainly due to insufficient endogenous H2 O2 or relatively high pH value for Fenton reaction-dependent ferroptosis, and the high redox level of tumor cells attenuates the oxidation therapy. Herein, an efficient lipid-based delivery system to load oxidation catalyst and glutathione peroxidase 4 (Gpx4) inhibitor is orchestrated, intending to amplify Fenton reaction-independent ferroptosis by bidirectional regulation of LPO accumulation. Ferric ammonium citrate (FAC), Gpx4 inhibitor sorafenib (SF), and unsaturated lipids are constructed into mPEG2K -DSPE-modified liposomes (Lip@SF&FAC). Influenced by the high level of intratumoral glutathione, FAC can be converted into Fe2+ , and subsequently the formed iron redox pair (Fe2+ /Fe3+ ) catalyzes unsaturated phospholipids of liposomes into LPO via a Fenton reaction-independent manner. Meanwhile, SF can downregulate LPO reduction by inhibiting Gpx4 activation. In vitro and in vivo antitumor experiments show that Lip@SF&FAC induces massive LPO accumulation in tumor cells and ultimately exhibits strong tumor-killing ability with negligible side effect. Consequently, this two-pronged approach provides a new ferroptosis strategy for predominant LPO accumulation and enhanced cancer therapy.

Lipid-Based Delivery Systems for Flavonoids and Flavonolignans: Liposomes, Nanoemulsions, and Solid Lipid Nanoparticles.

Herbal chemicals with a long history in medicine have attracted a lot of attention. Flavonolignans and flavonoids are considered as two classes of the above-mentioned compounds with different functional groups which exhibit several therapeutic capabilities such as antimicrobial, anti-inflammatory, antioxidant, antidiabetic, and anticancer activities. Based on the studies, high hydrophobic properties of the aforementioned compounds limit their bioavailability inside the human body and restrict their wide application. Nanoscale formulations such as solid lipid nanoparticles, liposomes, and other types of lipid-based delivery systems have been introduced to overcome the above-mentioned challenges. This approach allows the aforementioned hydrophobic therapeutic compounds to be encapsulated between hydrophobic structures, resulting in improving their bioavailability. The above-mentioned enhanced delivery system improves delivery to the targeted sites and reduces the daily required dosage. Lowering the required daily dose improves the performance of the drug by diminishing its side effects on non-targeted tissues. The present study aims to highlight the recent improvements in implementing lipid-based nanocarriers to deliver flavonolignans and flavonoids.

Breakthroughs and bottlenecks of psoriasis therapy: Emerging trends and advances in lipid based nano-drug delivery platforms for dermal and transdermal drug delivery

Psoriasis is a chronic autoimmune skin disease characterised by abnormal epidermal keratinocytes, hyperproliferation, and inflammatory infiltration. The main challenges that make treating psoriasis difficult are the complex aetiology, frequency of administration, and multiple side effects of traditional therapeutics. Clinicians often face difficulties while treating serious wounds caused by psoriasis. The therapeutic advantages of existing molecules can be maximised by administering them at the correct place for an extended period. Over the past two to three decades, there has been an increase in the availability of lipid-based nanocarriers for cosmetic and skin-care applications. However, there is still significant room for the development of additional lipid-based nanocarriers that are both highly biocompatible and capable of stimulating skin regeneration processes. This review discusses the contemporary trends and latest progress in research on various lipid-based nanodrug delivery systems employed for the effective management of psoriasis. Here, we first recapitulated skin structure and its function. Second, we discussed an overview of pathophysiology of psoriasis and challenges of existing therapies in psoriasis treatment. We outlined skin delivery through various lipid-based nano-drug delivery systems like liposomes, transferosomes, niosomes, ethosomes, transethosomes, phytosomes, solid lipid nanoparticles, cerosomes, glyceroethosomes, and spanlastics for the effective management of psoriasis. Finally, we outlined in vitro assays and models for anti-psoriatic activity assessment. It will assist clinicians and formulation scientists in treating skin diseases, particularly psoriasis.

Milk phospholipids and buttermilk based composite nanosystems for enhanced stability and bioaccessibility of β-carotene

Bioaccessibility of lipophilic β-carotene is often compromised and lipid-based colloidal delivery systems (CDS) are considered effective to overcome this issue. In this study, milk phospholipid (MPL), buttermilk powder (BMP) and MPL:BMP composite-nanosystems were developed with encapsulation-efficiency of 91 ± 2.7%. Scanning electron microscopy showed spherical morphology of MPL and MPL:BMP nanosystems; slightly irregular morphology was observed in BMP nanosystems. Dynamic light scattering (DLS) for size (172±5–217 ± 2 nm) and polydispersity-index (0.24–0.37) analyses were performed. Fourier-transform infrared spectroscopy confirmed β-carotene incorporated through weak electrostatic interaction in nanosystems. The lipid peroxidation inhibition capacity of β-carotene by thiobarbituric reactive substances (TBARS) assay revealed that MPL, BMP and MPL:BMP nanosystems effectively inhibited TBARS (20.6 ± 2.9–50 ± 4.5%) formation. In vitro digestion revealed chemical stability was 82 ± 2.4% while bioaccessibility and effective-bioaccessibility was 94.8 ± 5% and 70.5 ± 3.2% in MPL:BMP nanosystems, respectively. Thus, milk-ingredients-based CDS can provide rational design for nutraceuticals application with enhanced bioaccessibility of β-carotene.

Emerging Trends in Lipid-Based Vaccine Delivery: A Special Focus on Developmental Strategies, Fabrication Methods, and Applications

Lipid-based vaccine delivery systems such as the conventional liposomes, virosomes, bilosomes, vesosomes, pH-fusogenic liposomes, transferosomes, immuno-liposomes, ethosomes, and lipid nanoparticles have gained a remarkable interest in vaccine delivery due to their ability to render antigens in vesicular structures, that in turn prevents its enzymatic degradation in vivo. The particulate form of lipid-based nanocarriers confers immunostimulatory potential, making them ideal antigen carriers. Facilitation in the uptake of antigen-loaded nanocarriers, by the antigen-presenting cells and its subsequent presentation through the major histocompatibility complex molecules, leads to the activation of a cascade of immune responses. Further, such nanocarriers can be tailored to achieve the desired characteristics such as charge, size, size distribution, entrapment, and site-specificity through modifications in the composition of lipids and the selection of the appropriate method of preparation. This ultimately adds to its versatility as an effective vaccine delivery carrier. The current review focuses on the various lipid-based carriers that have been investigated to date as potential vaccine delivery systems, the factors that affect their efficacy, and their various methods of preparation. The emerging trends in lipid-based mRNA vaccines and lipid-based DNA vaccines have also been summarized.

Influence of 1,3-diacylglycerol on physicochemical and digestion properties of nanoemulsions and its enhancement of encapsulation and bioaccessibility of hydrophobic nobiletin.

Lipid-based delivery systems are commonly used to encapsulate hydrophobic bioactive compounds for enhancing their bioaccessibility and bioavailability, especially for triacylglycerol (TAG) oil-based delivery systems. However, studies on the development of 1,3-diacylglycerol (DAG) oil-based delivery systems are rather limited. Herein, the influence of 1,3-DAG oil as a carrier oil on the properties of nanoemulsions and the bioaccessibility of encapsulated hydrophobic nobiletin (NOB) were investigated. High-purity 1,3-DAG (over 93% pure) was prepared by a combination of enzymatic esterification and ethanol crystallization. 1,3-DAG oil as a carrier oil could be used to formulate nanoemulsions with smaller droplet size, narrower size distribution and similar stability compared to TAG oil. Importantly, 1,3-DAG oil could efficiently encapsulate high-loading NOB (1.45 mg g-1) in nanoemulsions and significantly improve the bioaccessibility of NOB (above 80%), which is attributable to its massive lipolysis and higher encapsulation capacity than TAG oil. Moreover, the addition of the 1,3-DAG component in TAG oil significantly improved the properties of nanoemulsions and the loading and bioaccessibility of NOB, especially as the 1,3-DAG content was not less than 50%. The structure of lipids (DAG versus TAG) influenced the nanoemulsion properties and the bioaccessibility of encapsulated NOB. Based on the good properties of 1,3-DAG oil coupled with its health benefits, 1,3-DAG oil-based nanoemulsion delivery systems have great prospects for improving and extending emulsion properties and bioactivity as well as bioaccessibility enhancement.

Administration methods of lipid-based nanoparticle delivery systems for cancer treatment.

As nano medications have developed in the recent four decades, nano-delivery systems have been applied in treating various diseases and are especially common in cancer treatment. Nano-delivery systems could target cancer-associated cells, enhance the accuracy and efficacy of treatment, and reduce systemic side effects. Among the many drugs on nano-carriers, the load system of lipid-based nanoparticles has the brightest prospect due to the high level of biocompatibility, biodegradability, loading capability, and immunogenicity. Previous reviews have comprehensively introduced their effects and progress. However, most of them did not provide great attention to practical applications. This article will focus on different intake methods, which decide the biological process of drugs. This suggests that we can modify lipid-based nano-delivery systems according to how they are capable of prolonging the half-life span and magnifying therapy effects in treating cancer. Besides, we put forth the problems that should be further studied in the future and their probable solutions.

PREFORMULATION STUDY OF CEFTRIAXONE AND CIPROFLOXACIN FOR LIPID BASED DRUG DELIVERY SYSTEMS

Several tests should be performed to rule out any potential physical or chemical interactions between the active pharmaceutical ingredient and the various excipients that might be utilized in the manufacturing of the drug formula. Fourier Transform infrared spectroscopy is a simple technique for the detection of changes within excipient-drug mixtures. In addition to speeding up the aging process of drugs and their possible interactions with excipients, isothermal stress testing was achieved. In this study, Ceftriaxone sodium (CTX), and Ciprofloxacin hydrochloride (CIPRO) as active ingredients were subjected to several tests to exclude any interaction with the excipients that could be used in the formulation of lipid base biodegradable antibiotic for prevention of post-operative infection. The compatibility was tested by using Fourier Transform infrared spectroscopy (FT-IR) and isothermal stability testing (IST). As a result, the IR spectral interpretation showed that the spectra obtained from the binary mixtures match the original spectra of API. Generally, there was no obvious and influential change of any characteristic peaks which confirms the absence of chemical interaction between the CTX or CIPRO and excipients. In the IST, the API – excipient mixture shows no significant change in physical properties. There was no change in color, gas formation, and liquefaction of the mixture stored under stress conditions. There was no significant change in the amount of API after storage in stressed conditions at statistical significance (p = 0.05). In conclusion, there are no notable interactions between API and the various excipients that could be employed to create biodegradable lipid-based delivery systems that are effective at preventing post-operative infection.

Lipid-Based Delivery Systems in Development of Genetic and Subunit Vaccines.

Lipidic carriers are composed of natural, synthetic, or physiological lipid/phospholipid materials. The flexibility of lipid-based delivery systems for transferring a variety of molecules such as immunomodulators, antigens, and drugs play a key role in design of effective vaccination and therapeutic strategies against infectious and non-infectious diseases. Genetic and subunit vaccines are two major groups of promising vaccines that have the potential for improving the protective potency against different diseases. These vaccine strategies rely greatly on delivery systems with various functions, including cargo protection, targeted delivery, high bioavailability, controlled release of antigens, selective induction of antigen-specific humoral or cellular immune responses, and low side effects. Lipidic carriers play a key role in local tissue distribution, retention, trafficking, uptake and processing by antigen-presenting cells. Moreover, lipid nanoparticles have successfully achieved to the clinic for the delivery of mRNA. Their broad potential was shown by the recent approval of COVID-19 mRNA vaccines. However, size, charge, architecture, and composition need to be characterized to develop a standard lipidic carrier. Regarding the major roles of lipid-based delivery systems in increasing the efficiency and safety of vaccine strategies against different diseases, this review concentrates on their recent advancements in preclinical and clinical trials.

Silibinin-Loaded Nanostructured Lipid Carriers for Growth Inhibition of Cisplatin-Resistant Ovarian Cancer Cells.

Cisplatin is the most often used chemotherapy in the treatment of ovarian cancer (OC), however long-term usage leads to drug resistance and treatment failure. Silibinin is a sparingly water-soluble natural compound with well-known anticancer effects. The use of lipid-based delivery systems is a potential approach for enhancing silibinin's water solubility. In this study, nanostructured lipid carriers (NLCs) containing silibinin were prepared and their inhibitory effects were tested in combination with cisplatin against sensitive/resistant A2780 OC cells. Silibinin-loaded NLCs (silibinin-NLCs) were prepared by the hot homogenization method, and their size, shape, zeta potential (ZP), and encapsulation efficiency (EE), as well as their inhibitory effects, were examined in combination with cisplatin against sensitive/resistant A2780 OC cells. Formulation of silibinin-NLCs using cocoa butter led to spherical-shaped NLCs with a size of 95 nm and EE of 98%. The ZP and the dispersion index of the silibinin-NLCs were -27.12 ± 0.13 mv and 0.12 ± 0.04, respectively. The release kinetics of silibinin-NLCs was best fitted with the zero-order model. The combination of cisplatin and silibinin-NLCs sensitized the cisplatin-resistant A2780 OC cells and exhibited a more synergistic inhibitory effect on A2780 cells as compared with the combination of cisplatin and plain silibinin. The optimized silibinin-NLCs can be considered a suitable drug delivery system for the inhibition of cisplatin-resistant OC cells.

Novel Self-Nanoemulsifying Drug Delivery System of Single Bulb Garlic: Stability, Toxicity, and Antiinflammation in 3T3-L1 Cells

Single bulb garlic (SBG) has the potential as an immunomodulator; however, it has low solubility and bioavailability. A lipid-based delivery system, that is, the self-nanoemulsifying drug delivery system (SNEDDS), offers a novel opportunity in drug delivery. SBG can be a suitable candidate for SNEDDS development. This research aims to describe the physical stability, toxicity test of the SNEDDS, and SNEDDS SBG potential as antiinflammation in 3T3-L1 cells. The SNEDDS is made with various ratios of concentrations of carrier oil, surfactants, and cosurfactants, namely, 0.50: 3.45: 0.96, and added with SBG extract (SBGE) of 20 mg/mL. The results of the response test of SNEDDS SBGE formulation indicate an average and standard deviation of emulsification time of 16.38±3.01 (second), pH 7.21±0.08, and transmittance of 98.40±0.23(%). The average nanoemulsion size is 14.333±0.416 nm, polydispersion index of 0.213±0.056, and zeta potential of -14.67±0.72 mV. The results of the physical stability test indicate no segregation, deposition, cracking, or creaming in all nanoemulsion samples and SNEDDS SBG. The MTT test in a dose of 62.5, 125, 250, 500, 100, 2000, and 4000 µg/mL suggests that the highest viability of the 3T3-L1 cells is at a dose of 2000 µg/mL, which is 97.83%±1.55%. Therefore, SNEDDS SBGE can be a potential candidate for oral preparation by increasing bioavailability and reducing toxicity in the 3T3-L1 cells. An antiinflammatory test on the TNF-𝛼 and IL-1𝛽 expressions influences the 3T3-L1 cells. the SNEDDS of SBGE has the potential to reduce the expression of TNF-𝛼 and IL-1𝛽 and increase IL-10 expression in the methylglyoxal-induced 3T3-L1 cells.

Incorporation of curcumin-loaded lipid-based nano delivery systems into food: Release behavior in food simulants and a case study of application in a beverage

Curcumin-loaded lipid-based nano delivery systems (nanoemulsions-NE, solid lipid nanoparticles-SLN and nanostructured lipid carriers-NLC) were subjected to different food simulants to evaluate curcumin’s in vitro release kinetics and particlés stability. The nano delivery systems were also incorporated into a model beverage and their physicochemical properties were evaluated during storing period. Curcumin’s bioaccessibility of beverages containing nano delivery systems were assessed through an in vitro digestion process. All nano delivery systems showed a higher curcumin’s release and lower particle stability at 50 % ethanol (lipophilic food simulant) comparatively to hydrophilic food simulants. NLC and SLN showed a good particle’s stability within the beverage during storing period, while NE presented high instability immediately after incorporation in the beverage. NLC and SLN did not affect beverage’s stability relatively to pH, however the beverage with NLC was slightly more stable regarding color. Beverage with SLN presented higher curcumin bioaccessibility compared to the beverage with NLC, however it showed lower curcumin’s stability.

Physical characterization of clove oil based self Nano-emulsifying formulations of cefpodoxime proxetil: Assessment of dissolution rate, antioxidant & antibacterial activity

Cefpodoxime proxetil (CPD) is a broad-spectrum cephalosporin widely indicated in respiratory tract infections like pneumonia. CPD is a BCS class IV drug with the constraint of low bioavailability attributable to its poor aqueous solubility (10µg/ml) and impaired permeability. Clove oil (CO) acts as a lipophilic additive for lipid-based delivery systems designed to facilitate dissolution characteristics of poorly soluble drugs, modulating drug permeability as well as stability against oxidation. The present work aims to improve CPD solubilization by developing CO-based fully dilutable self nano emulsifying formulation (SNF), and assessment of its antibacterial and antioxidant potential. The existence of nanoemulsion domains was tracked from ternary phase diagrams plotted between CO, Tween 20/PEG400 to act as oil phase, surfactant/co-surfactant (Smix) respectively at weight ratios 1:1, 1:2, and 2:1 whereas aqueous phase acted its tertiary component. Two subsets of SNF formulations coded as (DAO1-DAO5) and (DAM1-DAM3) were prepared and assessed for antioxidant and antibacterial activities respectively, along with their naive CO-counterparts (AO1-AO5) and (AM1- AM5) respectively. Physical characterization revealed SNFs were droplet size range 35-170nm, conductivities in the range 200-500uS/cm, and RI values in 1.361-1.429. The dilution-induced microstructure transition effect was observed in SNF with the addition of an aqueous phase as its oil-continuous domain transformed into water-continuous via bi-continuous structure formation as interpreted from conductivity and refractive index data. In-vitro dissolution characterization of SNF formulation exhibits a quick CPD release pattern in comparison to control in phosphate buffer at pH 6.8 and HCl buffer at pH3.0. SNF produced significant differences in the CPD release characteristics measured at different pH conditions in comparison to controls. These observations are plausible in terms of drug solubilization effect since SNFs possess a high proportion of surfactant and produce interfacial action on CO and CPD. Antioxidant activities in DAO and AO at CO 20, 40 & 100µg/ml levels were significantly different from controls as measured using the DPPH method. Comparison of antibacterial activity of DAMs against E. coli, B. subtilis, Enterobacter species, and S. aureus (scheme-II) vs CPD suspension or its coarse emulsion or even naive CO counterpart were statistically different and minimum inhibitory concentration of CPD was reduced in SNF formulations. These differences were well corroborated in the data exhibited in zones of inhibition studies. CO-based SNFs produced significantly improved dissolution characteristics of poorly soluble drugs like CPD and potentiated the antibacterial and antioxidant activities. Developed SNFs could be employed as Self nano emulsifying drug delivery systems (SNEDDS) for BCS class IV drugs.

Hiroshi Shiku, MD, PhD: In Memoriam (1943–2022)

Hiroshi Shiku, MD, PhD: In Memoriam (1943–2022)

Lipid-based nucleic acid therapeutics with in vivo efficacy.

Synthetic vectors for therapeutic nucleic acid delivery are currently competing significantly with their viral counter parts due to their reduced immunogenicity, large payload capacity, and ease of manufacture under GMP-compliant norms. The approval of Onpattro, a lipid-based siRNA therapeutic, and the proven clinical success of two lipid-based COVID-19 vaccines from Pfizer-BioNTech, and Moderna heralded the specific advantages of lipid-based systems among all other synthetic nucleic acid carriers. Lipid-based systems with diverse payloads-plasmid DNA (pDNA), antisense oligonucleotide (ASO), small interfering RNA (siRNA), microRNA (miRNA), small activating RNA (saRNA), and messenger RNA (mRNA)-are now becoming a mature technology, with growing impact in the clinic. Research over four decades identified the key factors determining the therapeutic success of these multi-component systems. Here, we discuss the main nucleic acid-based technologies, presenting their mechanism of action, delivery barriers facing them, the structural properties of the payload as well as the component lipids that regulate physicochemical properties, pharmacokinetics and biodistribution, efficacy, and toxicity of the resultant nanoparticles. We further detail on the formulation parameters, evolution of the manufacturing techniques that generate reproducible and scalable outputs, and key manufacturing aspects that enable control over physicochemical properties of the resultant particles. Preclinical applications of some of these formulations that were successfully translated from in vitro studies to animal models are subsequently discussed. Finally, clinical success and failure of these systems starting from 1993 to present are highlighted, in a holistic literature review focused on lipid-based nucleic acid delivery systems. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.