Microfluidic preparation of antimicrobial microparticles composed of l-lactide/1,3-dioxolane (co)polymers loaded with quercetin.

The resistance of microorganisms against commonly used antibiotics is becoming an increasingly important problem in the food and pharmaceutical industries. Therefore, the development of novel bactericidal agents, as well as the design of drug delivery systems based on materials composed of biocompatible and biodegradable building blocks, has attracted increasing attention. To address this challenge, microparticles composed of l-lactide homopolymer and l-lactide/1,3-dioxolane (co)polymers loaded with quercetin (Q) were fabricated by using a microfluidic technique. This method enables the preparation of homogeneous particles with sizes ranging from 60 to 80 µm, composed of degradable semicrystalline or amorphous (co)polyesters. The microencapsulation of Q in a (co)polymeric matrix enables prolonged release of the antimicrobial agent. The antibacterial properties of the obtained biocompatible microparticles are confirmed by the agar diffusion plate method for various bacterial strains. Therefore, Q-loaded microparticles can have important applications in food preservation as a novel antimicrobial system.

Stimulus-responsive nanomaterials under physical regulation for biomedical applications.

Cancer is a growing threat to human beings. Traditional treatments for malignant tumors usually involve invasive means to healthy human tissues, such as surgical treatment and chemotherapy. In recent years the use of specific stimulus-responsive materials in combination with some non-contact, non-invasive stimuli can lead to better efficacy and has become an important area of research. It promises to develop personalized treatment systems for four types of physical stimuli: light, ultrasound, magnetic field, and temperature. Nanomaterials that are responsive to these stimuli can be used to enhance drug delivery, cancer treatment, and tissue engineering. This paper reviews the principles of the stimuli mentioned above, their effects on materials, and how they work with nanomaterials. For this aim, we focus on specific applications in controlled drug release, cancer therapy, tissue engineering, and virus detection, with particular reference to recent photothermal, photodynamic, sonodynamic, magnetothermal, radiation, and other types of therapies. It is instructive for the future development of stimulus-responsive nanomaterials for these aspects.

Trivalent Subunit Vaccine Candidates for COVID-19 and Their Delivery Devices.

The COVID-19 pandemic highlights the need for platform technologies enabling rapid development of vaccines for emerging viral diseases. The current vaccines target the SARS-CoV-2 spike (S) protein and thus far have shown tremendous efficacy. However, the need for cold-chain distribution, a prime-boost administration schedule, and the emergence of variants of concern (VOCs) call for diligence in novel SARS-CoV-2 vaccine approaches. We studied 13 peptide epitopes from SARS-CoV-2 and identified three neutralizing epitopes that are highly conserved among the VOCs. Monovalent and trivalent COVID-19 vaccine candidates were formulated by chemical conjugation of the peptide epitopes to cowpea mosaic virus (CPMV) nanoparticles and virus-like particles (VLPs) derived from bacteriophage Qß. Efficacy of this approach was validated first using soluble vaccine candidates as solo or trivalent mixtures and subcutaneous prime-boost injection. The high thermal stability of our vaccine candidates allowed for formulation into single-dose injectable slow-release polymer implants, manufactured by melt extrusion, as well as microneedle (MN) patches, obtained through casting into micromolds, for prime-boost self-administration. Immunization of mice yielded high titers of antibodies against the target epitope and S protein, and data confirms that antibodies block receptor binding and neutralize SARS-CoV and SARS-CoV-2 against infection of human cells. We present a nanotechnology vaccine platform that is stable outside the cold-chain and can be formulated into delivery devices enabling single administration or self-administration. CPMV or Qß VLPs could be stockpiled, and epitopes exchanged to target new mutants or emergent diseases as the need arises.

Ethyl cellulose coated sustained release aspirin spherules for treating COVID-19: DOE led rapid optimization using arbitrary interface; applicable for emergency situations.

This work attempts to resolve one of the key issues related to the design and development of sustained-release spherule of aspirin for oral formulations, tailored to treat COVID-19. For that, in the Design of Experiments (DOE) an arbitrary interface, "coating efficiency" (CE) is introduced and scaled the cumulative percentage coating (CPC) to get predictable control over drug release (DR). Subsequently, the granules containing ASP are converted to spherules and then to Ethyl cellulose (EC) Coated spherules (CS) by a novel bed coating during the rolling (BCDR) process. Among spherules, one with 0.35 mm than 0.71 mm shows required properties. The CS has a low 1200 angle by Optical Microscopy (OM), smooth surface without cracks by scanning electron microscopy (SEM), and better flow properties (Angle of repose 29.69 ± 0.780, Carr's index 6.73 ± 2.24%, Hausner's Ratio 1.07 ± 0.03) than granules and spherules. Once certain structure-dependent control over release is attained (EC coated spherules shows 10% reduction in burst release (BR) than uncoated spherules showing a release of 80-91%) the predictability is achieved and Design of space (DOS) by DOE (CE-70.14%and CPC-200% and DR-61.54%) is established. The results of DOE to experimentally validated results were within 20% deviation. The aspirin is changing its crystal structure by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) from Form-I to Form-II showing polymorphism inside the drug reservoir with respect to the process. This CE and CPC approach in DOE can be used for delivery system design of other labile drugs similar to aspirin in emergency situations.

Multidomain drug delivery systems of ß-casein micelles for the local oral co-administration of antiretroviral combinations.

The antiretroviral (ARV) cocktailrevolved the treatment of the human immunodeficiency virus (HIV) infection. Drug combinations have been also tested to treat other infectious diseases, including the recentcoronavirus disease 2019 (COVID-19) outbreak. To simplify administration fixed-dose combinationshave been introduced, however, oral anti-HIV therapy still struggles with low oral bioavailability of many ARVs.This work investigated the co-encapsulation of two clinically relevant ARV combinations,tipranavir (TPV):efavirenz (EFV) anddarunavir (DRV):efavirenz (EFV):ritonavir (RTV),within the core of ß-casein (bCN) micelles. Encapsulation efficiency in both systems was ~100%. Cryo-transmission electron microscopy and dynamic light scattering of the ARV-loaded colloidaldispersions indicatefull preservation of the spherical morphology, and x-ray diffraction confirm that the encapsulated drugs are amorphous. To prolong the physicochemical stabilitythe formulations were freeze-driedwithout cryo/lyoprotectant, and successfully redispersed, with minor changes in morphology.Then, theARV-loaded micelles were encapsulated within microparticles of Eudragit® L100, which prevented enzymatic degradation and minimized drug release under gastric-like pH conditionsin vitro. At intestinal pH, the coating polymer dissolved and released the nanocarriers and content. Overall, our results confirm the promise of this flexible and modular technology platform for oral delivery of fixed dose combinations.

Antiviral Essential Oils Incorporated in Nanocarriers: Strategy for Prevention from COVID-19 and Future Infectious Pandemics.

BACKGROUND: Coronavirus has become a life-threatening disease and it is caused by severe acute respiratory syndrome (SARS). This new strain of coronavirus is not completely understood and to date, there is no treatment for coronavirus. Traditional ayurvedic medicines, mainly essential oils and Chinese herbs, have always played a vital role in the prevention and treatment of several epidemics and pandemics. In the meantime, guidelines of the ministry of AYUSH (Ayurveda, yoga, unani, siddha and homoepathy) include a traditional medicinal treatment for flu and fever and also recommended to boost immunity to prevent the spread of coronavirus. It is not possible to find which essential oil will offer the best level of protection. However, it is likely to assume that some essential oils are likely to offer a measurable level of defense in the same way they do with many other known viruses. METHODS: Literature relevant to various essential oils having antiviral activity has been collected and compiled. Various nanocarriers of essential oils have also been stated. The database was collected using various search engines such as J-Gate, Google Scholar, Sci-Hub, PubMed, ScienceDirect, etc. Results: Essential oils contain active constituents such as phenolic compounds, terpenoids, alkaloids, phenyl propanoids, etc., which are responsible for their biological properties such as antiviral, antibacterial, antimicrobial, antioxidant activities and many more. However, the use of essential oils has always been limited due to poor solubility, solvent toxicity, volatility and low solubility. Many nanotechnology based carriers especially, liposomes, dendrimers, nanoparticles, nanoemulsion and microemulsion, etc. have been evidenced to overcome limitations associated with essential oils. CONCLUSION: Several essential oils possess potent antiviral activity and are characterized by fewer side effects and are safe for human use. The nanocarrier systems of these oils have proved the potential to treat viral and bacterial infections. Lay Summary: Current COVID-19 era demands traditional treatment for immunity boost up as support therapy. Traditional ayurvedic medicines, mainly essential oils and Chinese herbs, have always played a vital role in the prevention and treatment of several epidemics and pandemics. Therefore, authors have summarized various essential oils having antiviral activity in current manuscript. Various nanocarriers of essential oils have been reported. Essential oils contain active constituents such as phenolic compounds, terpenoids, alkaloids, phenyl propanoids, etc., which are responsible for their biological properties such as antiviral, antibacterial, antimicrobial, antioxidant activity. However, the use of essential oils has always been limited due to poor solubility, solvent toxicity, volatility and low solubility. Many nanotechnology based carriers especially, liposomes, dendrimers, nanoparticles, nanoemulsion and microemulsion, etc. have been evidenced to overcome limitations associated with essential oils. The nanocarrier systems of these oils have proved the potential to treat viral and bacterial infections.

Overcoming the paracetamol dose challenge with wrinkled mesoporous carbon spheres.

Paracetamol is the most commonly used antipyretic and analgesic drug in the world. The key challenge in paracetamol therapy is associated with the frequency of the dosing. Depending on the gastric filling within 10-20 min paracetamol is released and rapidly absorbed from the gastrointestinal tract. Therefore, it must be taken three or four times a day. To address the dose challenge it is desirable that the paracetamol release profile follows the zero-order kinetic model (constant rate of drug release per unit time). This goal can be achieved by using a suitable porous carrier system. Herein, non-toxic wrinkled mesoporous carbons with unique morphology were synthesized via the hard template method as new carriers for paracetamol. These particles can precisely modulate the release of paracetamol over 24 h in a simulated gastric fluid according to the zero-order kinetic model completely eliminating the initial burst release. Overall, these systems could significantly enhance the bioavailability of paracetamol and prolong its therapeutic effect in numerous diseases such as cold, flu, COVID-19, and severe pain.