Search Results (20)

The efficient oral delivery of therapeutic proteins and peptides poses a tremendous challenge due to their inherent instability, large molecular size, and susceptibility to enzymatic degradation. Several nanocarrier systems, such as liposomes, solid lipid nanoparticles, and polymeric nanoparticles, have been explored to overcome these problems. Liposomes and other lipid-based nanocarriers show excellent biocompatibility and the ability to encapsulate hydrophobic and hydrophilic drugs; however, they often suffer from poor structural stability, premature leakage of the loaded drugs, and poor encapsulation efficiency for macromolecular peptides and proteins. On the other hand, polymeric nanoparticles are more stable and allow better control over drug release; nevertheless, they usually lack the necessary biocompatibility and cellular uptake efficiency. Recently, lipid-polymer hybrid nanoparticles (LPHNs) have emerged as an advanced solution combining the structural stability of polymers and the biocompatibility and surface functionalities of lipids to enhance the controlled release, stability, and bioavailability of protein and peptide drugs. In this review, an attempt was made to set a clear definition of the LPHNs and extend the concept and area, so to our knowledge, this is the first review that highlights six categories of the LPHNs based on their anatomy. Moreover, this review offers a detailed analysis of LPHN preparation methods, including conventional and nonconventional one-step and two-step processes, nanoprecipitation, microfluidic mixing, and emulsification methods. Moreover, the material attributes and critical process parameters affecting the output of the preparation methods were illustrated with supporting examples to enable researchers to select the suitable preparation method, excipients, and parameters to be manipulated to get the LPHNs with the predetermined quality. The number of reviews focusing on the formulation of peptide/protein pharmaceutics usually focus on a specific drug like insulin. To our knowledge, this is the first review that generally discusses LPHN-based delivery of biopharmaceuticals. by discussing representative examples of previous reports comparing them to a variety of nanocarrier systems to show the potentiality of the LPHNs to deliver peptides and proteins. Moreover, some ideas and suggestions were proposed by the authors to tackle some of the shortcomings highlighted in these studies. By presenting this comprehensive overview of LPHN preparation strategies and critically analyzing literature studies on this topic and pointing out their strong and weak points, this review has shown the gaps and enlightened avenues for future research. Full article

Cancer is considered as the second leading cause of death worldwide. Chemotherapy, radiotherapy, immunotherapy, and targeted drug delivery are the main treatment options for treating cancers. Chemotherapy drugs are either available for oral or parenteral use. Oral chemotherapy, also known as chemotherapy at home, is more likely to improve patient compliance and convenience. Oral anti-cancer drugs have bioavailability issues associated with lower aqueous solubility, first-pass metabolism, poor intestinal permeability and drug absorption, and degradation of the drug throughout its journey in the gastrointestinal tract. A highly developed carrier system known as lipid polymer hybrid nanoparticles (LPHNs) has been introduced. These nanocarriers enhance drug stability, solubility, and absorption, and reduce first-pass metabolism. Consequently, this will have a positive impact on oral bioavailability enhancement. This article provides an in-depth analysis of LPHNs as a novel drug delivery system for anti-cancer agents. It discusses an overview of the limited bioavailability of anti-cancer drugs, their reasons and consequences, LPHNs based anti-cancer drug delivery, conventional and modern preparation methods as well as their drug loading and entrapment efficiencies. In addition, this article also gives an insight into the mechanistic approach to oral bioavailability enhancement, potential applications in anti-cancer drug delivery, limitations, and future prospects of LPHNs in anti-cancer drug delivery. Full article

Edaravone is one of the treatment options for Amyotrophic Lateral Sclerosis, but its therapeutic efficacy is limited due to the incapacity to cross the blood–brain barrier, as well as its short life span and poor stability, which is ultimately caused by its tautomerism in physiological condions. This work presents an overview about the use of several nanoformulations based on polymeric, protein, lipidic, or hybrid structure as suitable and stable drug delivery systems for encapsulating edaravone. We also evaluated the functionalization of nanoparticles with pegylated chains using the polyethylene glycol or tocopherol polyethylene glycol succinate and the possibility of preparing polymeric nanoparticles at different pH (7.4, 9, and 11). Edaravone was sucessfully encapsulated in polymeric, lipid–polymer hybrid, and lipidic nanoparticles. The use of higher pH values in the synthesis of polymeric nanoparticles has led to a decrease in nanoparticle size and an increase in the percentage of encapsulation efficiency. However, the resulting nanoformulations are not stable. Only polymeric and hybrid nanoparticles showed good stability over 80 days of storage, mainly at 4 °C. Overall, the nanoformulations tested did not show cytotoxicity in the SH-SY5Y cell line except the nanostructured lipid carrier formulations that showed some cytotoxicity possibly due to lipidic peroxidation. In conclusion, this work shows that edaravone can be encapsulated in different nanocarriers that could act as an interesting alternative for the treatment of Amyotrophic Lateral Sclerosis. Full article

Gene therapy holds great promise for treating prostate cancer unresponsive to conventional therapies. However, the lack of delivery systems that can transport therapeutic DNA and drugs while targeting tumors without harming healthy tissues presents a significant challenge. This study aimed to explore the potential of novel hybrid lipid nanoparticles, composed of biocompatible zein and conjugated to the cancer-targeting ligand transferrin. These nanoparticles were designed to entrap the anti-cancer drug docetaxel and carry plasmid DNA, with the objective of improving the delivery of therapeutic payloads to prostate cancer cells, thereby enhancing their anti-proliferative efficacy and gene expression levels. These transferrin-bearing, zein-based hybrid lipid nanoparticles efficiently entrapped docetaxel, leading to increased uptake by PC-3 and LNCaP cancer cells and significantly enhancing anti-proliferative efficacy at docetaxel concentrations exceeding 1 µg/mL. Furthermore, they demonstrated proficient DNA condensation, exceeding 80% at polymer–DNA weight ratios of 1500:1 and 2000:1. This resulted in increased gene expression across all tested cell lines, with the highest transfection levels up to 11-fold higher than those observed with controls, in LNCaP cells. These novel transferrin-bearing, zein-based hybrid lipid nanoparticles therefore exhibit promising potential as drug and gene delivery systems for prostate cancer therapy. Full article

In recent years, the field of drug delivery has seen a significant shift towards the exploration and utilization of nanoparticles (NPs) as versatile carriers for therapeutic agents. With its ability to provide exact control over NPs’ characteristics, microfluidics has emerged as a potent platform for the efficient and controlled synthesis of NPs. Microfluidic devices designed for precise fluid manipulation at the micro-scale offer a unique platform for tailoring NP properties, enabling enhanced control over NP properties such as size, morphology, and size distribution while ensuring high batch-to-batch reproducibility. Microfluidics can be used to produce liposomes, solid lipid nanoparticles, polymer-based NPs, and lipid-polymer hybrid NPs, as well as a variety of inorganic NPs such as silica, metal, metal oxide, quantum dots, and carbon-based NPs, offering precise control over composition and surface properties. Its unique precision in tailoring NP properties holds great promise for advancing NP-based drug delivery systems in both clinical and industrial settings. Although challenges with large-scale production still remain, microfluidics offers a transformative approach to NP synthesis. In this review, starting from the historical development of microfluidic systems, the materials used to create the systems, microfabrication methods, and system components will be discussed in order to provide the reader with an overview of microfluidic systems. In the following, studies on the fabrication of nanoparticles such as lipid NPs, polymeric NPs, and inorganic NPs in microfluidic devices are included. Full article

This review discusses receptor-binding domain (RBD) mutations related to the emergence of various SARS-CoV-2 variants, which have been highlighted as a major cause of repetitive clinical waves of COVID-19. Our perusal of the literature reveals that most variants were able to escape neutralizing antibodies developed after immunization or natural exposure, pointing to the need for a sustainable technological solution to overcome this crisis. This review, therefore, focuses on nanotechnology and the development of antiviral nanomaterials with physical antagonistic features of viral replication checkpoints as such a solution. Our detailed discussion of SARS-CoV-2 replication and pathogenesis highlights four distinct checkpoints, the S protein (ACE2 receptor coupling), the RBD motif (ACE2 receptor coupling), ACE2 coupling, and the S protein cleavage site, as targets for the development of nano-enabled solutions that, for example, prevent viral attachment and fusion with the host cell by either blocking viral RBD/spike proteins or cellular ACE2 receptors. As proof of this concept, we highlight applications of several nanomaterials, such as metal and metal oxide nanoparticles, carbon-based nanoparticles, carbon nanotubes, fullerene, carbon dots, quantum dots, polymeric nanoparticles, lipid-based, polymer-based, lipid–polymer hybrid-based, surface-modified nanoparticles that have already been employed to control viral infections. These nanoparticles were developed to inhibit receptor-mediated host–virus attachments and cell fusion, the uncoating of the virus, viral gene expression, protein synthesis, the assembly of progeny viral particles, and the release of the virion. Moreover, nanomaterials have been used as antiviral drug carriers and vaccines, and nano-enabled sensors have already been shown to enable fast, sensitive, and label-free real-time diagnosis of viral infections. Nano-biosensors could, therefore, also be useful in the remote testing and tracking of patients, while nanocarriers probed with target tissue could facilitate the targeted delivery of antiviral drugs to infected cells, tissues, organs, or systems while avoiding unwanted exposure of non-target tissues. Antiviral nanoparticles can also be applied to sanitizers, clothing, facemasks, and other personal protective equipment to minimize horizontal spread. We believe that the nanotechnology-enabled solutions described in this review will enable us to control repeated SAR-CoV-2 waves caused by antibody escape mutations. Full article

Small interfering RNA (siRNA) molecules have limited transfection efficiency and stability, necessitating the use of delivery systems to be effective in gene knockdown therapies. In this regard, lipid–polymeric nanocarriers have emerged as a promising class of nanoparticles for siRNA delivery, particularly for topical applications. We proposed the use of solid lipid–polymer hybrid nanoparticles (SLPHNs) as topical delivery systems for siRNA. This approach was evaluated by assessing the ability of SLPHNs–siRNA complexes to internalize siRNA molecules and both to penetrate skin layers in vitro and induce gene knocking down in a skin cell line. The SLPHNs were formed by a specific composition of solid lipids, a surfactant polymer as a dispersive agent, and a cationic polymer as a complexing agent for siRNA. The optimized nanocarriers exhibited a spherical shape with a smooth surface. The average diameter of the nanoparticles was found to be 200 nm, and the zeta potential was measured to be +20 mV. Furthermore, these nanocarriers demonstrated excellent stability when stored at 4 °C over a period of 90 days. In vitro and in vivo permeation studies showed that SLPHNs increased the cutaneous penetration of fluorescent-labeled siRNA, which reached deeper skin layers. Efficacy studies were conducted on keratinocytes and fibroblasts, showing that SLPHNs maintained cell viability and high cellular uptake. Furthermore, SLPHNs complexed with siRNA against Firefly luciferase (siLuc) reduced luciferase expression, proving the efficacy of this nanocarrier in providing adequate intracellular release of siRNA for silencing specific genes. Based on these results, the developed carriers are promising siRNA delivery systems for skin disease therapy. Full article

Poly(ethylene oxide)-poly(ε-caprolactone) (PEO-PCL) is a family of block (or graft) copolymers with several biomedical applications. These types of copolymers are well-known for their good biocompatibility and biodegradability properties, being ideal for biomedical applications and for the formation of a variety of nanosystems intended for controlled drug release. The aim of this review is to present the applications and the properties of different nanocarriers derived from PEO-PCL block and graft copolymers. Micelles, polymeric nanoparticles, drug conjugates, nanocapsules, and hybrid polymer-lipid nanoparticles, such as hybrid liposomes, are the main categories of PEO-PCL based nanocarriers loaded with different active ingredients. The advantages and the limitations in preclinical studies are also discussed in depth. PEO-PCL based nanocarriers could be the next generation of delivery systems with fast clinical translation. Finally, current challenges and future perspectives of the PEO-PCL based nanocarriers are highlighted. Full article

Skin wounds have imposed serious socioeconomic burdens on healthcare providers and patients. There are just more than 25,000 burn injury-related deaths reported each year. Conventional treatments do not often allow the re-establishment of the function of affected regions and structures, resulting in dehydration and wound infections. Many nanocarriers, such as lipid-based systems or biobased and biodegradable polymers and their associated platforms, are favorable in wound healing due to their ability to promote cell adhesion and migration, thus improving wound healing and reducing scarring. Hence, many researchers have focused on developing new wound dressings based on such compounds with desirable effects. However, when applied in wound healing, some problems occur, such as the high cost of public health, novel treatments emphasizing reduced healthcare costs, and increasing quality of treatment outcomes. The integrated hybrid systems of lipid-based nanocarriers (LNCs) and polymer-based systems can be promising as the solution for the above problems in the wound healing process. Furthermore, novel drug delivery systems showed more effective release of therapeutic agents, suitable mimicking of the physiological environment, and improvement in the function of the single system. This review highlights recent advances in lipid-based systems and the role of lipid-based carriers and biodegradable polymers in wound healing. Full article

Nanotechnology takes the lead in providing new therapeutic options for cancer patients. In the last decades, lipid-based nanoparticles—solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), liposomes, and lipid–polymer hybrid nanoparticles—have received particular interest in anticancer drug delivery to solid tumors. To improve selectivity for target cells and, thus, therapeutic efficacy, lipid nanoparticles have been functionalized with antibodies that bind to receptors overexpressed in angiogenic endothelial cells or cancer cells. Most papers dealing with the preclinical results of antibody-conjugated nanoparticles claim low systemic toxicity and effective tumor inhibition, which have not been successfully translated into clinical use yet. This review aims to summarize the current “state-of-the-art” in anticancer drug delivery using antibody-functionalized lipid-based nanoparticles. It includes an update on promising candidates that entered clinical trials and some explanations for low translation success. Full article

According to the WHO, cancer caused almost 10 million deaths worldwide in 2020, i.e., almost one in six deaths. Among the most common are breast, lung, colon and rectal and prostate cancers. Although the diagnosis is more perfect and spectrum of available drugs is large, there is a clear trend of an increase in cancer that ends fatally. A major advance in treatment was the introduction of gentler antineoplastics for targeted therapy–tyrosine kinase inhibitors (TKIs). Although they have undoubtedly revolutionized oncology and hematology, they have significant side effects and limited efficacy. In addition to the design of new TKIs with improved pharmacokinetic and safety profiles, and being more resistant to the development of drug resistance, high expectations are placed on the reformulation of TKIs into various drug delivery lipid-based nanosystems. This review provides an insight into the history of chemotherapy, a brief overview of the development of TKIs for the treatment of cancer and their mechanism of action and summarizes the results of the applications of self-nanoemulsifying drug delivery systems, nanoemulsions, liposomes, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles and nanostructured lipid carriers used as drug delivery systems of TKIs obtained in vitro and in vivo. Full article

Targeted delivery of therapeutics to specific tissues is critically important for reducing systemic toxicity and optimizing therapeutic efficacy, especially in the case of cytotoxic drugs. Many strategies currently exist for targeting systemically administered drugs, and ultrasound-controlled targeting is a rapidly advancing strategy for externally-stimulated drug delivery. In this non-invasive method, ultrasound waves penetrate through tissue and stimulate gas-filled microbubbles, resulting in bubble rupture and biophysical effects that power delivery of attached cargo to surrounding cells. Drug delivery capabilities from ultrasound-sensitive microbubbles are greatly expanded when nanocarrier particles are attached to the bubble surface, and cargo loading is determined by the physicochemical properties of the nanoparticles. This review serves to highlight and discuss current microbubble–nanoparticle complex component materials and designs for ultrasound-mediated drug delivery. Nanocarriers that have been complexed with microbubbles for drug delivery include lipid-based, polymeric, lipid–polymer hybrid, protein, and inorganic nanoparticles. Several schemes exist for linking nanoparticles to microbubbles for efficient nanoparticle delivery, including biotin–avidin bridging, electrostatic bonding, and covalent linkages. When compared to unstimulated delivery, ultrasound-mediated cargo delivery enables enhanced cell uptake and accumulation of cargo in target organs and can result in improved therapeutic outcomes. These ultrasound-responsive delivery complexes can also be designed to facilitate other methods of targeting, including bioactive targeting ligands and responsivity to light or magnetic fields, and multi-level targeting can enhance therapeutic efficacy. Microbubble–nanoparticle complexes present a versatile platform for controlled drug delivery via ultrasound, allowing for enhanced tissue penetration and minimally invasive therapy. Future perspectives for application of this platform are also discussed in this review. Full article

Hesperidin is a bioflavonoid constituent that among many other biological activities shows significant wound healing properties. However, the bioavailability of hesperidin when applied topically is limited due to its low solubility and systemic absorption, so novel dosage forms are needed to improve its therapeutic efficacy. The objectives of this study were to develop hesperidin-loaded lipid-polymer hybrid nanoparticles (HLPHNs) to enhance the delivery of hesperidin to endogenous sites in the wound bed and promote the efficacy of hesperidin. HLPHNs were optimized by response surface methodology (RSM) using the Box-Behnken design. HLPHNs were prepared using an emulsion-solvent evaporation method based on a double emulsion of water-in-oil-in-water (w/o/w) followed by freeze-drying to obtain nanoparticles. The prepared formulations were characterized using various evaluation parameters. In addition, the antioxidant activity of HLPHN 4 was investigated in vitro using the DPPH model. Seventeen different HLPHNs were prepared and the HLPHN4 exhibited the best mean particle size distribution, zeta potential, drug release and entrapment efficiency. The values are 91.43 nm, +23 mV, 79.97% and 92.8%, respectively. Transmission electron microscope showed similar spherical morphology as HLPHN4. Differential scanning calorimetry verified the physical stability of the loaded drug in a hybrid system. In vitro release studies showed uniform release of the drug over 24 h. HLPHN4 showed potent antioxidant activity in vitro in the DPPH model. The results of this study suggest that HLPHNs can achieve sustained release of the drug at the wound site and exhibit potent in vitro antioxidant activity. Full article

Chikungunya is an infectious disease caused by mosquito-transmitted chikungunya virus (CHIKV). It was reported that NS1 and E2 siRNAs administration demonstrated CHIKV inhibition in in vitro as well as in vivo systems. Cationic lipids are promising for designing safe non-viral vectors and are beneficial in treating chikungunya. In this study, nanodelivery systems (hybrid polymeric/solid lipid nanoparticles) using cationic lipids (stearylamine, C9 lipid, and dioctadecylamine) and polymers (branched PEI-g-PEG -PEG) were prepared, characterized, and complexed with siRNA. The four developed delivery systems (F1, F2, F3, and F4) were assessed for stability and potential toxicities against CHIKV. In comparison to the other nanodelivery systems, F4 containing stearylamine (Octadecylamine; ODA), with an induced optimum cationic charge of 45.7 mV in the range of 152.1 nm, allowed maximum siRNA complexation, better stability, and higher transfection, with strong inhibition against the E2 and NS1 genes of CHIKV. The study concludes that cationic lipid-like ODA with ease of synthesis and characterization showed maximum complexation by structural condensation of siRNA owing to high transfection alone. Synergistic inhibition of CHIKV along with siRNA was demonstrated in both in vitro and in vivo models. Therefore, ODA-based cationic lipid nanoparticles can be explored as safe, potent, and efficient nonviral vectors overcoming siRNA in vivo complexities against chikungunya. Full article

Baricitinib (BTB) is an orally administered Janus kinase inhibitor, therapeutically used for the treatment of rheumatoid arthritis. Recently it has also been approved for the treatment of COVID-19 infection. In this study, four different BTB-loaded lipids (stearin)-polymer (Poly(d,l-lactide-co-glycolide)) hybrid nanoparticles (B-PLN1 to B-PLN4) were prepared by the single-step nanoprecipitation method. Next, they were characterised in terms of physicochemical properties such as particle size, zeta potential (ζP), polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL). Based on preliminary evaluation, the B-PLN4 was regarded as the optimised formulation with particle size (272 ± 7.6 nm), PDI (0.225), ζP (−36.5 ± 3.1 mV), %EE (71.6 ± 1.5%) and %DL (2.87 ± 0.42%). This formulation (B-PLN4) was further assessed concerning morphology, in vitro release, and in vivo pharmacokinetic studies in rats. The in vitro release profile exhibited a sustained release pattern well-fitted by the Korsmeyer–Peppas kinetic model (R² = 0.879). The in vivo pharmacokinetic data showed an enhancement (2.92 times more) in bioavailability in comparison to the normal suspension of pure BTB. These data concluded that the formulated lipid-polymer hybrid nanoparticles could be a promising drug delivery option to enhance the bioavailability of BTB. Overall, this study provides a scientific basis for future studies on the entrapment efficiency of lipid-polymer hybrid systems as promising carriers for overcoming pharmacokinetic limitations. Full article