Technological Strategies Applied to Pharmaceutical Systems for Intranasal Administration of Drugs Intended for Neurological Treatments: A Review.

The complexity of treating neurological diseases has meant that new strategies have had to be developed to deliver drugs to the brain more efficiently and safely. Intranasal drug delivery is characterized by its ease of administration, safety, and rapid delivery directly from the nose to the brain. Several strategies have been developed to improve the delivery of drugs to the brain via nasal administration. These include the use of mucoadhesive and thermoresponsive polymers and their combination into polymer blends, as well as the use of liposomes, niosomes, and nano- and microemulsions. Therefore, this review focuses on technologies for developing pharmaceutical systems aimed at delivery via the nose to the brain, contributing to new treatments for difficult neurological disorders. Some of the most common and difficult-to-treat neurological conditions, the intranasal route of administration, and the anatomy of the nasal cavity have been discussed, as well as factors that may influence the absorption of drugs administered into the nose. The types of intranasal formulations and the devices that can be used to administer these products are also discussed in this review. Strategies for improving the transport of bioactive agents and increasing bioavailability are highlighted. The technologies discussed in this review can facilitate the development of formulations with improved properties, such as drug release and mucoadhesiveness, which have several advantages for patients requiring complex neurological treatments.

Using food to color food: photostability of canistel pulp and its application as a food dye.

The use of foods to color other foods (coloring food) should be considered in food production. In this study, freeze-dried canistel (Pouteria campechiana (Kunth) Baehni) pulp underwent a photostability test. A blue LED light with a maximum intensity of 420 nm was utilized to induce photodegradation of the pulp. After irradiation, the samples were analyzed using photoacoustic spectroscopy. Different concentrations (2%, 4%, and 6%) of the pulp were employed as coloring food in ice cream, and the ice cream was thoroughly characterized. Photoacoustic spectroscopy provided valuable insights into dehydrated canistel pulp, revealing two stages of photoreaction involving carotenoids (violaxanthin and ξ-carotene) and demonstrating photostability under visible LED irradiation. The ice cream made with natural food dye produce elevated levels of bioactive compounds and retained a stable color throughout storage. All ice creams exhibited thixotropy. Ice creams with higher pulp concentrations displayed greater resistance to shear stress and, in sensory tests, received the highest scores, attributed to their intense yellow color. Dehydrated canistel pulp holds significant potential for use as food coloring in the industry due to its photostability. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-024-05991-5.

Development of nanostructured environmentally responsive system containing hydroxypropyl methylcellulose for nose-to-brain administration of meloxicam.

The intranasal administration of drugs using environmentally responsive formulations, employing a combination of hydroxypropyl methylcellulose (HPMC) and poloxamer 407 (P407), can result in release systems that may assist in the treatment of neurological diseases. Meloxicam, considered a potential adjuvant in the treatment of Alzheimer's disease, could be used in these platforms. The aim of this work was to develop a mucoadhesive, thermoresponsive, and nanostructured system containing HPMC for nose-to-brain administration of meloxicam. The initially selected systems were investigated for their rheological, mechanical, and micellar size characteristics. The systems were dilatant at 25 °C and pseudoplastic with a yield value at 37 °C, showing viscoelastic properties at both temperatures. The platform containing HPMC (0.1%, w/w) and P407 (17.5%, w/w) was selected and demonstrated good mucoadhesive properties, along with an appropriate in vitro release profile. HPMC could form a binary system with P407, displaying superior mucoadhesive and thermoresponsive properties for nose-to-brain meloxicam administration, indicating that the selected formulation is worthy of clinical studies.

Boosting the photodynamic activity of erythrosine B by using thermoresponsive and adhesive systems containing cellulose derivatives for topical delivery.

Erythrosine displays potential photodynamic activity against microorganisms and unhealthy cells. However, erythrosine has high hydrophilicity, negatively impacting on permeation through biological membranes. Combining biological macromolecules and thermoresponsive polymers may overcome these erythrosine-related issues, enhancing retention of topically applied drugs. The aim of this work was to investigate the performance of adhesive and thermoresponsive micellar polymeric systems, containing erythrosine in neutral (ERI) or disodium salt (ERIs) states. Optimized combinations of poloxamer 407 (polox407) and sodium carboxymethylcellulose (NaCMC) or hydroxypropyl methylcellulose (HPMC) were used as platforms for ERI/ERIs delivery. The rheological and mechanical properties of the systems was explored. Most of the formulations were plastic, thixotropic and viscoelastic at 37 °C, with suitable gelation temperature for in situ gelation. Mechanical parameters were reduced in the presence of the photosensitizer, improving the softness index. Bioadhesion was efficient for all hydrogels, with improved parameters for mucosa in contrast to skin. Formulations composed of 17.5 % polox407 and 3 % HPMC or 1 % NaCMC with 1 % (w/w) ERI/ERIs could release the photosensitizer, reaching different layers of the skin/mucosa, ensuring enough production of cytotoxic species for photodynamic therapy. Functional micelles could boost the photodynamic activity of ERI and ERIs, improving their delivery and contact time with the cells.

Drug Delivery Platforms Containing Thermoresponsive Polymers and Mucoadhesive Cellulose Derivatives: A Review of Patents.

Nowadays, the development of mucoadhesive systems for drug delivery has gained keen interest, with enormous potential in applications through different routes. Mucoadhesion characterizes an attractive interaction between the pharmaceutical dosage form and the mucosal surface. Many polymers have shown the ability to interact with mucus, increasing the residence time of local and/or systemic administered preparations, such as tablets, patches, semi-solids, and micro and nanoparticles. Cellulose is the most abundant polymer on the earth. It is widely used in the pharmaceutical industry as an inert pharmaceutical ingredient, mainly in its covalently modified forms: methylcellulose, ethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and carboxymethylcellulose salts. Aiming to overcome the drawbacks of oral, ocular, nasal, vaginal, and rectal routes and thereby maintaining patient compliance, innovative polymer blends have gained the interest of the pharmaceutical industry. Combining mucoadhesive and thermoresponsive polymers allows for simultaneous in situ gelation and mucoadhesion, thus enhancing the retention of the system at the site of administration and drug availability. Thermoresponsive polymers have the ability to change physicochemical properties triggered by temperature, which is particularly interesting considering the physiological temperature. The present review provides an analysis of the main characteristics and applications of cellulose derivatives as mucoadhesive polymers and their use in blends together with thermoresponsive polymers, aiming at platforms for drug delivery. Patents were reviewed, categorized, and discussed, focusing on the applications and pharmaceutical dosage forms using this innovative strategy. This review manuscript also provides a detailed introduction to the topic and a perspective on further developments.

Design and Optimization of Stimuli-responsive Emulsion-filled Gel for Topical Delivery of Copaiba Oil-resin.

This study presents a phytotherapeutic emulsion-filled gel design composed of Pluronic® F127, Carbopol® C934P, and high level of copaiba oil-resin (PHY-ECO). Mathematical modeling and response surface methodology (RSM) were employed to access the optimal ratio between the oil and the polymer gel-matrix constituents. The chemometric approach showed robust mechanical and thermoresponsive properties for emulsion gel. The model predicts viscosity parameters at 35.0°C (skin temperature) from PHY-ECOs. Optimized PHY-ECOs were described by 18-20% (w/w) F127, 0.25% (w/w) C934P, and 15% (w/w) copaiba oil-resin, and showed interfacial layers properties that led to high physicochemical stability. Besides, it had thermal stimuli-responsive that led large viscosity range before and after skin administration, observed by oscillatory rheology. These behaviors give the optimized smart PHY-ECO high design potential to be used as a pharmaceutical platform for CO delivery, focusing on the anti-inflammatory therapy and skin wound care.

Thermo and Photoresponsive Emulgel Loaded with Copaifera reticulata Ducke and Chlorophylls: Rheological, Mechanical, Photodynamic and Drug Delivery Properties in Human Skin.

Recently, the number of new cases of cutaneous leishmaniasis has been of concern among health agencies. Research that offers new therapeutic alternatives is advantageous, especially those that develop innovative drugs. Therefore, this paper presents the incorporation of Copaifera reticulata Ducke and chlorophyll extract into Pluronic®® F127 and Carbopol gels, under optimized polymer quantities. The chlorophyll extract (rich in photosensitizing compounds) was obtained by continuous-flow pressurized liquid extraction (PLE), a clean, environmentally friendly method. The system aims to act as as a leishmanicidal, cicatrizant, and antibiotic agent, with reinforcement of the photodynamic therapy (PDT) action. Rheological and mechanical analyses, permeation studies and bioadhesiveness analyses on human skin, and PDT-mediated activation of Staphylococcus aureus were performed. The emulgels showed gelation between 13° and 15 °C, besides pseudoplastic and viscoelastic properties. Furthermore, the systems showed transdermal potential, by releasing chlorophylls and C. reticulata Ducke into the deep layers of human skin, with good bioadhesive performance. The application of PDT reduced three logarithmic colony-forming units of S. aureus bacteria. The results support the potential of the natural drug for future clinical trials in treating wounds and cutaneous leishmania.

Development of buccal film formulations and their mucoadhesive performance in biomimetic models.

When developing buccal films for oromucosal drug administration, adhesion is essential to ensure sufficient time for permeation of the active ingredient(s) through the oral mucosa and avoid the detachment and subsequent swallowing of the film. In this study, biomimetic materials were evaluated as a replacement for buccal mucosa in mucoadhesion testing and potential adhesives were compared regarding their suitability to increase the adhesion of hypromellose-based oromucosal films. Gelatin gels, as possible biomimetics, failed to mimic the buccal mucosa. Furthermore, esophageal tissue lead to a wider variance of adhesion data despite showing a good correlation with buccal tissue. A synthetic copolymer hydrogel based on hydroxyethylmethacrylate (HEMA) and N-acryloyl glucosamine (AGA) was able to mimic the buccal mucosa in these tests and reduced the variation in the data compared to animal tissue. Adding polyacrylic acid and polyvinylpyrrolidone to the film formulations at a concentration of 5% w/w approximately doubled the maximum detachment force and work of adhesion. Sodium alginate enhanced the adhesive properties moderately but adding chitosan did not significantly increase mucoadhesion. Polyvinylpyrrolidone and polyacrylic acid are rated as strong adhesion enhancers for buccal films and the HEMA/AGA hydrogel is considered as a suitable alternative for animal mucosa in mucoadhesion testing.

Interaction between mucoadhesive cellulose derivatives and Pluronic F127: Investigation on the micelle structure and mucoadhesive performance.

Systems composed of bioadhesive and thermoresponsive polymers can combine in situ gelation with bio/mucoadhesion, enhancing retention of topically applied drugs. The effect of bioadhesive sodium carboxymethylcellulose (NaCMC) and hydroxypropyl methylcellulose cellulose (HPMC) on the properties of thermoresponsive Pluronic® F127 (F127) was explored, including micellization and the mucoadhesion. A computational analysis between these polymers and their molecular interactions were also studied, rationalising the design of improved binary polymeric systems for pharmaceutical and biomedical applications. The morphological characterization of polymeric systems was conducted by SEM. DSC analysis was used to investigate the crystallization and micellization enthalpy of F127 and the mixed systems. Micelle size measurements and TEM micrographs allowed for investigation into the interference of cellulose derivatives on F127 micellization. Both cellulose derivatives reduced the critical micellar concentration and enthalpy of micellization of F127, altering hydrodynamic diameters of the aggregates. Mucoadhesion performance was useful to select the best systems for mucosal application. The systems composed of 17.5% (w/w) F127 and 3% (w/w) HPMC or 1% (w/w) NaCMC are promising as topical drug delivery systems, mainly on mucosal surfaces. They were biocompatible when tested against Artemia salina, and also able to release a model of hydrophilic drug in a controlled manner.

Preclinical study of methotrexate-based hydrogels versus surfactant based liquid crystal systems on psoriasis treatment.

Psoriasis is an autoimmune, inflammatory and chronic skin disease in which cell growth and proliferation are increased, causing erythema, lesions and skin's peeling. Oral methotrexate (MTX) is the first-choice drug when phototherapy or retinoid treatment are not effective. Topical administration can be advantageous to better orientate the drug's delivery; however, the stratum corneum performs as a barrier for hydrofilic drugs penetration. This study sought to evaluate two different types of vehicles for MTX on the psoriasis treatment - hydrogel and liquid crystal systems (LCs). Lamellar and hexagonal liquid crystalline phases were selected from a ternary phase diagram based on polysorbate 80, isopropyl miristate and water. The hydrogel was based on alkylated carbomer (ACH). Rheological analysis showed ACH was more elastic than lamellar and hexagonal phases. ACH interacted better with pig skin than LCs in bioadhesion assay. Preclinical study revealed the ACH decreased inflammation in mice with induced psoriasis, being as effective as dexamethasone to regulate epidermis thickness, COX-2 and myeloperoxidase activity and TNF-α level, while LCs demonstrated inflammatory effect. Therefore, MTX-loaded hydrogel based platforms are indicated for local treatment of psoriasis and present great potential for further studies.

Acacia mearnsii gum: A residue as an alternative gum Arabic for food stabilizer.

Acacia mearnsii gum is not commercially exploited, being characterized as residue from A. mearnsii cultivation. This work investigated the A. mearnsii gum polysaccharide composition, its cytotoxicity and the technological effect as a stabilizer in ice cream. A. mearnsii gum showed a similar chemical structure to commercial gum Arabic and did not decrease the viability and proliferation of fibroblast cells (Balb/3T3) and hepatocarcinoma (HepG2). Rheological tests showed that the ice cream stabilized by the A. mearnsii gum had a more structured system (more interactions between the mixture components) and the same melting characteristics as the ice cream samples made with commercial gum Arabic. The results showed that A. mearnsii gum, which is actually an agro-industrial residue from tannin production for industry, is a potential stabilizing gum for the food industry, contributing to the economic development of the exploitation chain of A. mearnsii products and by-products.

Thermoresponsive systems composed of poloxamer 407 and HPMC or NaCMC: mechanical, rheological and sol-gel transition analysis.

Poloxamer 407 (polox407) is widely studied as thermogelling polymer, transitioning to a gel state when warmed Polox407 forms weak hydrogels with rapid dissolution in excess solvent. This study reports the development of binary systems composed of polox407 and hydroxypropyl methylcellulose (HPMC) or sodium carboxymethylcellulose (NaCMC) aiming to improve the rheological and mechanical properties of the hydrogel. The interaction between polox407 and cellulose derivatives was studied, and their interaction with biological surfaces predicted. The carbohydrates affected the mechanical and rheological behavior of polox407 in different ways, dependent on polymer type, concentration, and temperature. Tsol/gel and rheological interaction parameters were useful to select the most suitable formulations for topical or local application. Most of the binary systems exhibited plastic behavior, thixotropy and viscoelastic properties. Appropriate formulations were identified for local application, such as 17.5/3; 17.5/4; 20/3 and 20/4 (%, w/w) for polox407/HPMC; and 17.5/1; 17.5/1.5; 20/1 and 20/1.5 (%, w/w) for polox407/NaCMC.

Photodynamic Therapy of Psoriasis Using Photosensitizers of Vegetable Origin.

Psoriasis is an immune-mediated, chronic and recurrent inflammatory skin disease, prevalent worldwide, and represents an important burden in life quality of patients. The most common clinical variant is termed as psoriasis vulgaris or plaque psoriasis, which with an individualized and carefully monitored therapy can decrease the patients' morbidity and improving their life quality. The aim is to achieve disease control, minimize the adverse drug effects, and tailor the treatment to individual patient factors. Photodynamic therapy (PDT) is based on local or systemic administration of a non-toxic photosensitizer followed by irradiation with a particular wavelength to generate reactive oxygen species (ROS), mainly highly cytotoxic singlet oxygen (1O2). The generation of these species results in the attack to substrates involved in biological cycles causing necrosis and apoptosis of affected tissues. Photosensitizers are found in natural products and also obtained by partial syntheses from abundant natural starting compounds. They can be isolated at low cost and in large amounts from plants or algae. Therefore, this manuscript reviews the use of molecules from vegetal sources as photosensitizer agents for the PDT of psoriasis. Psoriasis pathogenesis, management and treatment were reviewed. PDT principles, fundamentals and utilization for the treatment of psoriasis were also discussed. Photosensitizers for PDT of psoriasis are also reviewed focusing on those from vegetal sources. Despite the PDT is utilized for the treatment of psoriasis, very little amount of photosensitizers from plant sources are utilized, such as chlorophyll derivatives and hypericin; however, other natural photosensitizers such as curcumin, could also be investigated. They could constitute a very important, safe and cheap alternative for the successful photodynamic treatment of psoriasis.

Design of a nanostructured mucoadhesive system containing curcumin for buccal application: from physicochemical to biological aspects.

Mucoadhesive nanostructured systems comprising poloxamer 407 and Carbopol 974P® have already demonstrated good mucoadhesion, as well as improved mechanical and rheological properties. Curcumin displays excellent biological activity, mainly in oral squamous cancer; however, its physicochemical characteristics hinder its application. Therefore, the aim of this study was to develop nanostructured formulations containing curcumin for oral cancer therapy. The photophysical interactions between curcumin and the formulations were elucidated by incorporation kinetics and location studies. They revealed that the drug was quickly incorporated and located in the hydrophobic portion of nanometer-sized polymeric micelles. Moreover, the systems displayed plastic behavior with rheopexy characteristics at 37 °C, viscoelastic properties and a gelation temperature of 36 °C, which ensures increased retention after application in the oral cavity. The mucoadhesion results confirmed the previous findings with the nanostructured systems showing a residence time of 20 min in porcine oral mucosa under flow system conditions. Curcumin was released after 8 h and could permeate through the porcine oral mucosa. Cytotoxicity testing revealed that the formulations were selective to cancer cells over healthy cells. Therefore, these systems could improve the physicochemical characteristics of curcumin by providing improved release and permeation, while selectivity targeting cancer cells.

A mucosa-mimetic material for the mucoadhesion testing of thermogelling semi-solids.

Mucosa-mimetic materials are synthetic substrates which aim to replace animal tissue in mucoadhesion experiments. One potential mucosa-mimetic material is a hydrogel comprised of N-acryloyl-d-glucosamine and 2-hydroxyethylmethacrylate, which has been investigated as a surrogate for animal mucosae in the mucoadhesion testing of tablets and solution formulations. This study aims to investigate the efficacy of this mucosa-mimetic material in the testing of thermogelling semi-solid formulations, which transition from solution to gel upon warming. Two methods for assessing mucoadhesion have been used; tensile testing and a flow-through system, which allow for investigation under dramatically different conditions. It was found that the mucosa-mimetic material was a good surrogate for buccal mucosa using both testing methods. This material may be used to replace animal tissue in these experiments, potentially reducing the number of laboratory animals used in studies of this type.

The importance of the relationship between mechanical analyses and rheometry of mucoadhesive thermoresponsive polymeric materials for biomedical applications.

Pluronic F127® was associated with a carbomer homopolymer type B, as a model polymer blend to evidence the information provided by rheological and mechanical analyses on the development of bioadhesive thermoresponsive systems. The mechanical analysis enabled to observe that 20% (w/w) Pluronic F127®-polymer blends were harder, more adhesive, more mucoadhesive, more compressive and less soft. In addition, continuous flow rheometry demonstrated that the systems were plastic with rheopexy (15%, w/w, Pluronic F127®) or thixotropic (20%, w/w, Pluronic F127®). Oscillatory rheometry exhibited the increase of temperature, and the polymeric concentration increases the elasticity of the formulations. Moreover, correlation index showed that softness and textural analysis can be correlated and complementary, whereas adhesiveness cannot be correlated to mucoadhesion and is less specific. Rheological interaction parameter and gelation temperature showed that 15/0.25-polymer blend is suitable for pharmaceutical and biomedical application, since it can be administered in the liquid form and be gelled in the application site with proper mucoadhesion that can suggest an improved clinical efficacy. Therefore, the mechanical and rheological analyses are useful to characterize and select the best bioadhesive thermoresponsive formulation for the proposed treatment with improved performance.

Linear correlation between rheological, mechanical and mucoadhesive properties of polycarbophil polymer blends for biomedical applications.

Polycarbophil is widely used in a variety of pharmaceutical formulations, mainly for their strong ability to adhere to the epithelial and mucous barriers (bio/mucoadhesion). On the other hand, its association with the thermoresponsive polymer (poloxamer 407) has been poorly explored. This work investigates the rheological, mechanical and mucoadhesive properties of polymer blends containing polycarbophil and poloxamer 407, in order to select the best formulations for biomedical and pharmaceutical applications. Mechanical (hardness, compressibility, adhesiveness, softness, and mucoadhesion) and rheological characteristics (consistency index, yield value and hysteresis area) showed that 20% (w/w) poloxamer 407- polymer blends exhibited higher values parameters. However, the rheological interaction parameter, which was more sensible than the mechanical interaction parameter, revealed higher synergism for systems comprising 15% (w/w) poloxamer 407, due to the system organization and polymers' properties. Furthermore, gelation temperatures were appropriated, suggesting that polymer blends can be used as biomedical materials, and displaying easy administration, enhanced retention and prolonged residence time at the site of application. Therefore, rheological, mechanical and mucoadhesive characterization provided a rational basis for selecting appropriated systems, useful for mucoadhesive drug delivery systems and biomedical applications.

Defective neutralizing antibody response to SARS-CoV-2 in vaccinated dialysis patients

Patients on dialysis are at risk of severe course of SARS-CoV-2 infection. Understanding the neutralizing activity and coverage of SARS-CoV-2 variants of vaccine-elicited antibodies is required to guide prophylactic and therapeutic COVID-19 interventions in this frail population. By analyzing plasma samples from 130 hemodialysis and 13 peritoneal dialysis patients after two doses of BNT162b2 or mRNA-1273 vaccines, we found that 35% of the patients had low-level or undetectable IgG antibodies to SARS-CoV-2 Spike (S). Neutralizing antibodies against the vaccine-matched SARS-CoV-2 and Delta variant were low or undetectable in 49% and 77% of patients, respectively, and were further reduced against other emerging variants. The fraction of non-responding patients was higher in SARS-CoV-2-naive hemodialysis patients immunized with BNT162b2 (66%) than those immunized with mRNA-1273 (23%). The reduced neutralizing activity correlated with low antibody avidity. Patients followed up to 7 months after vaccination showed a rapid decay of the antibody response with an average 21- and 10-fold reduction of neutralizing antibodies to vaccine-matched SARS-CoV-2 and Delta variant, which increased the fraction of non-responders to 84% and 90%, respectively. These data indicate that dialysis patients should be prioritized for additional vaccination boosts. Nevertheless, their antibody response to SARS-CoV-2 must be continuously monitored to adopt the best prophylactic and therapeutic strategy.

SARS-CoV-2 immune evasion by variant B.1.427/B.1.429

SARS-CoV-2 entry is mediated by the spike (S) glycoprotein which contains the receptor-binding domain (RBD) and the N-terminal domain (NTD) as the two main targets of neutralizing antibodies (Abs). A novel variant of concern (VOC) named CAL.20C (B.1.427/B.1.429) was originally detected in California and is currently spreading throughout the US and 29 additional countries. It is unclear whether antibody responses to SARS-CoV-2 infection or to the prototypic Wuhan-1 isolate-based vaccines will be impacted by the three B.1.427/B.1.429 S mutations: S13I, W152C and L452R. Here, we assessed neutralizing Ab responses following natural infection or mRNA vaccination using pseudoviruses expressing the wildtype or the B.1.427/B.1.429 S protein. Plasma from vaccinated or convalescent individuals exhibited neutralizing titers, which were reduced 3-6 fold against the B.1.427/B.1.429 variant relative to wildtype pseudoviruses. The RBD L452R mutation reduced or abolished neutralizing activity of 14 out of 35 RBD-specific monoclonal antibodies (mAbs), including three clinical-stage mAbs. Furthermore, we observed a complete loss of B.1.427/B.1.429 neutralization for a panel of mAbs targeting the N-terminal domain due to a large structural rearrangement of the NTD antigenic supersite involving an S13I-mediated shift of the signal peptide cleavage site. These data warrant closer monitoring of signal peptide variants and their involvement in immune evasion and show that Abs directed to the NTD impose a selection pressure driving SARS-CoV-2 viral evolution through conventional and unconventional escape mechanisms.

Impact of SARS-CoV-2 B.1.1.7 Spike variant on neutralisation potency of sera from individuals vaccinated with Pfizer vaccine BNT162b2

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) transmission is uncontrolled in many parts of the world, compounded in some areas by higher transmission potential of the B1.1.7 variant now seen in 50 countries. It is unclear whether responses to SARS-CoV-2 vaccines based on the prototypic strain will be impacted by mutations found in B.1.1.7. Here we assessed immune responses following vaccination with mRNA-based vaccine BNT162b2. We measured neutralising antibody responses following a single immunization using pseudoviruses expressing the wild-type Spike protein or the 8 amino acid mutations found in the B.1.1.7 spike protein. The vaccine sera exhibited a broad range of neutralising titres against the wild-type pseudoviruses that were modestly reduced against B.1.1.7 variant. This reduction was also evident in sera from some convalescent patients. Decreased B.1.1.7 neutralisation was also observed with monoclonal antibodies targeting the N-terminal domain (9 out of 10), the Receptor Binding Motif (RBM) (5 out of 31), but not in neutralising mAbs binding outside the RBM. Introduction of the E484K mutation in a B.1.1.7 background to reflect newly emerging viruses in the UK led to a more substantial loss of neutralising activity by vaccine-elicited antibodies and mAbs (19 out of 31) over that conferred by the B.1.1.7 mutations alone. E484K emergence on a B.1.1.7 background represents a threat to the vaccine BNT162b.