Mucoadhesive Properties Research Articles

Preparation and Evaluation of pH-Sensitive Chitosan/Alginate Nanohybrid Mucoadhesive Hydrogel Beads: An Effective Approach to a Gastro-Retentive Drug Delivery System

Background: Despite extensive research over the decades, cancer therapy is still a great challenge because of the non-specific delivery of chemotherapeutic agents, which could be overcome by limiting the distribution of chemotherapeutic agents toward cancer cells. Objective: To reduce the cytolytic effects against cancer cells, graphene oxide (GO) nanoparticles (NPs) can load anticancer medicines and genetic tools. Methodology: During the current study, folic-acid-conjugated graphene oxide (Fa-GO) hybrid mucoadhesive chitosan (CS)-based hydrogel beads were fabricated through an “ion-gelation process”, which allows for regulated medication release at malignant pH. Results: The fabricated chitosan–alginate (SA-CS) hydrogel beads were examined using surface morphology, optical microscopy, XRD, FTIR, and homogeneity analysis techniques. The size analysis indicated that the size of the Fa-GO was up to 554.2 ± 95.14 nm, whereas the beads were of a micrometer size. The folic acid conjugation was confirmed by NMR. The results showed that the craggy edges of the graphene oxide were successfully encapsulated in a polymeric matrix. The mucoadhesive properties were enhanced with the increase in the CS concentration. The nanohybrid SA-CS beads exhibited good swelling properties, and the drug release was 68.29% at pH 5.6 during a 24 h investigation. The accelerated stability study, according to ICH guidelines, indicated that the hydrogel beads have a shelf-life of more than two years. Conclusions: Based on the achieved results, it can be concluded that this novel gastro-retentive delivery system may be a viable and different way to improve the stomach retention of anticancer agents and enhance their therapeutic effectiveness.

Development of paroxetine loaded nanotransferosomal gel for intranasal delivery with enhanced antidepressant activity in rats

The aim of this study was to develop paroxetine (PXT) loaded nanotransferosomal gel (PXT-NTFG) for intranasal brain delivery. The process involved fabricating PXT-NTFs (paroxetine-loaded nanotransferosomes) through a thin film hydration method and optimizing them based on parameters such as particle size (PS), zeta potential (ZP), polydispersity index (PDI), and entrapment efficiency (EE). The optimized PXT-NTFs exhibited uniform morphology with a PS of 158.30 ± 2.73 nm, low PDI (0.142 ± 0.072), high ZP (21.00 ± 0.75 mV), and excellent EE (88.09 ± 3.40 %). Characterization through various techniques confirmed the incorporation of PXT into the nanotransferosomes and its conversion to amorphous state. Moreover, PXT-NTFG was formulated with suitable viscosity and mucoadhesive properties. In vitro release studies demonstrated sustained drug release from PXT-NTFG at different pH levels as compared to PXT-NTFs and NTF dispersion. Similarly, ex vivo experiments showed 4 folds enhanced drug permeation from PXT-NTFG when compared with PXT conventional gel. Stability studies indicated that the optimized PXT-NTFs remained stable for four months at 4°C and 25°C. Additionally, improved behavioral outcomes, increased neuronal survival rates, and upregulated brain-derived neurotrophic factor (BDNF) expression was observed in lipopolysaccharide (LPS) induced depressed Sprague-Dawley rats after treatment with PXT-NTFG as compared to PXT-dispersion treated and untreated LPS-control groups. Notably, the formulation led to a significant reduction in brain and plasma TNF-α levels. In conclusion, intranasal PXT-NTFG is a promising formulation with sustained drug release, improved brain targeting and enhanced antidepressant activity.

Formulation and Evaluation of Clotrimazole Mucoadhesive Vaginal Globules

The aim of this study was to prepare vaginal suppositories with mucoadhesive properties to prolong the action of antifungal component clotrimazole (CLO). This was achieved by preparing vaginal pessaries on a hydrophilic gel base composed of gelatin and gelatin enriched with PEG 400 (in a 1:1 ratio), and then checking the properties of the obtained vaginal drugs. The prepared globules, containing 100 mg of CLO, were characterized in terms of mass and swelling index, organoleptic analysis was also prepared. In addition, a texture analysis and a study of the dissolution of clotrimazole were performed. On the basis of the obtained results, it was concluded that the modification of the composition of the gelatin–glycerin base by the addition of macrogol had a positive effect on the mucoadhesive properties of the globules. In addition, due to the presence of PEG 400, the globules were stiffer. It was also observed that the presence of CLO reduces the value of the force needed for compression during the texture analysis study. Comparing the CLO release profiles of the prepared globules and commercially available clotrimazole tablets, the release profile for the globules was slower than for the tablets, which indicates the possibility of using mucoadhesive globules as a form of a drug that releases the medicinal substance more slowly at the site of administration.

Chitosan-Based Nanoformulations: Preclinical Investigations, Theranostic Advancements, and Clinical Trial Prospects for Targeting Diverse Pathologies.

Chitosan, a biocompatible and biodegradable polymer, has attracted significant interest in the development of nanoformulations for targeted drug delivery and therapeutic applications. The versatility of chitosan lies in its modifiable functional groups, which can be tailored to diverse applications. Nanoparticles derived from chitosan and its derivatives typically exhibit a positive surface charge and mucoadhesive properties, enabling them to adhere to negatively charged biological membranes and gradually release therapeutic agents. This comprehensive review investigates the manifold roles of chitosan-based nanocarriers, ranging from preclinical research to theranostic applications and clinical trials, across a spectrum of diseases, including neurological disorders, cardiovascular diseases, cancer, wound healing, gastrointestinal disorders, and pulmonary diseases. The exploration starts with an overview of preclinical studies, emphasizing the potential of chitosan-based nanoformulations in optimizing drug delivery, improving therapeutic outcomes, and mitigating adverse effects in various disease categories. Advancements in theranostic applications of chitosan-based nanoformulations highlight their adaptability to diverse diseases. As these nanoformulations progress toward clinical translation, this review also addresses the regulatory challenges associated with their development and proposes potential solutions.

Functionalisation of chitosan with methacryloyl and crotonoyl groups as a strategy to enhance its mucoadhesive properties

Mucoadhesive polymers are crucial for prolonging drug retention on mucosal surfaces. This study focuses on synthesising and characterising novel derivatives by reacting chitosan with crotonic and methacrylic anhydrides. The structure of the resulting derivatives was confirmed using proton-nuclear magnetic resonance spectroscopy and Fourier-transform infrared spectroscopy. It was established that the degree of substitution plays a crucial role in the pH-dependent solubility profiles and electrophoretic mobility of the chitosan derivatives. Spray-drying chitosan solutions enabled preparation of microparticles, whose mucoadhesive properties were evaluated using fluorescence flow-through studies and tensile test, demonstrating improved retention on sheep nasal mucosa for modified derivatives. Acute toxicity studies conducted in vivo using planaria and in vitro using MTT assay with the Caco-2 cell line, a model of the mucosal epithelium in vitro, showed that the novel derivatives are not cytotoxic. These findings emphasise the potential of tailored chitosan chemical modifications for enhancing transmucosal drug delivery.

Mucoadhesive polyelectrolyte complexes of fucoidan and chitin nanowhiskers to prolong the antiprotozoal activity of metronidazole

The improvement of the specific pharmacological activity of agents with antimicrobial and antiprotozoal properties (e.g. metronidazole, MET) is of interest for clinical applications in the treatment of bacterial infections. In this work, we prepared the polyelectrolyte complexes (PEC) based on chitin nanowhiskers (CNW) and fucoidan (FUC) with hydrodynamic diameters of 244 and 816 nm, a ζ-potential of about −22 mV and good mucoadhesive properties. The incorporation of MET into PEC particles promoted the sustained release of MET for 10 h and maintained the antiprotozoal activity against clinical isolates of Trichomonas vaginalis for up to 10 h. At concentrations of 1–3 mg/mL (HeLa cell line), the CWN-FUC-MET particles showed no cytotoxicity. The sustained drug release rate, combined with pronounced mucoadhesive properties, improved pharmacological activity, and non-cytotoxicity makes the developed biopolymer delivery systems promising candidates for further clinical trials.

Design Formulation of Nanospanlastic Novel Carriers as a Promising Approach to Enhanced Bioavailability in Intranasal Drug Delivery for Sinusitis: Statistical Optimization and In vitro and In vivo Characterization

Background: Most new biologically active chemicals require better water solubility and slower dissolution rates. Cefdinir (CFD) has a very low bioavailability in its crystalline form and is poorly soluble in water. Objective: By preparing cefdinir's spanlastic nanovesicles (SNVs) using the ethanol injection method, the current study has attempted to enhance the drug's solubility and bioavailability using a statistical design approach. Methods: Independent variables, including the nonionic surfactant concentration, edge activator (EA), sonication time, SNVs entrapment efficiency, particle size, zeta potential, PDI, and in vitro release, have been evaluated. The best CFD-SNVs were positioned within in situ gel with muco-adhesive properties made of hydroxypropyl methylcellulose and deacetylated gellan gum. By contrasting intranasal injection of the produced gel with an IV solution, animal models have been used to investigate CFD's systemic and cerebral dynamics. Results: Statistical analysis has suggested an ideal SNVs formulation with nonionic surfactant (65 mg), EA (15 mg), and sonication (3 min). The sol-gel temperature for forming the mucoad-hesive in situ gel containing SNVs has been found to be 34.03°C, and 18.36 minutes has been the extended mucociliary transit time. Following intranasal injection, compared to SNV dispersion, the gelling system has exhibited higher brain bioavailability (2251.9 ± 75 vs. 5281.6 ± 51%, re-spectively). The gel has also demonstrated effective drug targeting of the brain with higher direct transport percentage indices. Conclusion: Mucoadhesive in situ gel with CFD-loaded SNVs can be administered via the in-tranasal route. To enhance bioavailability in the brain and drug targeting from the nose to the brain, nasal in situ gel loaded with CFD-SNVs could be a new carrier to be employed in sinusitis.

Sources and Methods for the Production of Xyloglucan, a Promising Stimulus-Sensitive Biopolymer: A Review.

Xyloglucan is a highly promising 'green' polymer that has found its application in the food and pharmaceutical industries. Due to its molecular structure similarity to mucin, it has remarkable mucoadhesion properties, which has led to a high research interest in this excipient for the development of transmucosal delivery systems. Thermosensitivity is another promising property of xyloglucan derivatives, which is mainly exhibited by synthetic block copolymers such as pluronics and PLGA derivatives. Delivery systems whose mechanism of active ingredient release is based on temperature sensitivity are widely used in many medical fields, ranging from antitumour therapy to intranasal delivery. Thus, conducting research on the possibility of obtaining and using a new mucoadhesive, fully biocompatible and affordable polymer-xyloglucan-is a promising task.

Delivery system for dexamethasone phosphate based on a Zn2+-crosslinked polyelectrolyte complex of diethylaminoethyl chitosan and chondroitin sulfate

Hybrid nano- and microparticles based on metal ion crosslinked biopolymers are promising carriers for the development of drug delivery systems with improved biopharmaceutical properties. In this work, dexamethasone phosphate-containing particles based on chondroitin sulfate and chitosan or diethylaminoethyl chitosan additionally crosslinked with Zn2+ were prepared. Depending on the polycation/polyanion ratio in the system, anionic and cationic polyelectrolyte complexes (PECs) were obtained. The anionic Zn2+-containing and Zn2+-free PECs had sizes of 154 and 180 nm and ζ-potentials of −22.4 and −27.5 mV, respectively. The cationic Zn2+-containing and Zn2+-free PECs had sizes of 242 and 362 nm and ζ-potentials of 22.4 and 24.7 mV, respectively. The presence of Zn2+ in the system significantly prolonged the release of dexamethasone phosphate from the hybrid polyelectrolyte particle. The resulting release profiles of dexamethasone phosphate were in agreement with the Peppas-Sahlin kinetic model, which considers the combined effects of Fickian diffusion and polymer chain relaxation on the drug release rate. It was shown that the prolongation of drug release was mainly due to swelling and relaxation of the Zn2+ crosslinked polymers. The developed particles exhibited good mucoadhesive properties and pronounced anti-inflammatory activity, making them attractive candidates for biomedical applications.

The Design of Novel 3D-Printed, Moulded, and Oral Viscous Budesonide Formulations for Paediatrics: A Comparative Evaluation of Their Mucoadhesive Properties.

Paediatric eosinophilic oesophagitis (EoE) treatment is challenging due to the limited number of age-appropriate formulations. This study aims to develop and evaluate oral viscous suspensions and solid formulations of budesonide (BUD), focusing on their in vitro mucoadhesive properties, to enhance drug delivery and therapeutic outcomes in paediatric EoE. This study encompasses the development of oral viscous suspensions and orodispersible solid formulations (moulded tablets and 3D-printed dosage forms) containing BUD. The formulations underwent quality control tests as per the European Pharmacopoeia, chemical stability assessments, and an in vitro evaluation of their mucoadhesiveness properties. A validated analytical method enabled accurate BUD quantification and efficient extraction, and all developed formulations demonstrated chemical stability for 30 days, meeting Ph. Eur. quality standards. Three-dimensional printing using SSE successfully produced 1 mg and 0.5 mg BUD printlets, complying with quality tests for conventional tablets. Formulations containing xanthan gum (L2-XG and P1-0.5-XG) exhibited superior mucoadhesive properties. L2-XG showed significantly higher mucoadhesion than L1-MC. Among the solid formulations, P1-0.5-XG demonstrated the highest mucoadhesive properties. This is the first study to develop solid oral dosage forms of BUD at a very low dose, specifically for paediatric use. The results highlight the potential of 3D printing for developing individualised orodispersible BUD formulations with improved bioadhesion for paediatric EoE treatment. The L2-XG formulation and the XG-containing printlets are the most promising formulations in terms of increasing contact time with the oesophageal mucosa, which could translate into improved therapeutic efficacy in this patient population.

Poly(Lactic-co-Glycolic Acid Nanoparticles Loaded with Docetaxel and Coated with Chitosan, Carboxymethyl Chitosan, or Glycol Chitosan.

Docetaxel (DTX) is a chemotherapeutic drug that has high toxicity and low bioavailability. To solve these problems, PLGA nanoparticles (NPs) were loaded with DTX and coated with mucoadhesive polymers; chitosan (CS), carboxymethyl chitosan (CMCS), or glycol chitosan(GCS). The NPs were characterized for size, charge, and polydispersity. The particles were explored using SEM, FTIR, DSC, and XRD. In vitro studies were performed to evaluate the mucoadhesive properties of the NPs and the drug release. The results validated the successful formation of spherical and monodispersed DTX NPs. The coated NPs exhibited highly positive charges, reaching +44.30±0.21 mV, whereas the uncoated NPs were almost neutral. The formulations demonstrated excellent encapsulation efficiency (>98%) and loading capacity (>45%). All polymers used in the coating process enhanced the mucoadhesive properties of PLGA NPs and sustained DTX release. Both the mucoadhesiveness and release were related to the used coating polymer and its concentration. The formulations were stable for up to three months in the refrigerator. In conclusion, loading DTX in PLGA NPs and coating them with CS, CMCS, or GCS provides a promising strategy to increase the NPs' residence time on mucosal surfaces, which is expected to decrease the required dose of DTX and reduce its side effects.

Formulation and Evaluation of Glipizide-loaded Mucoadhesive Microparticle Using Salvia hispanica Seeds Mucilage as Co-polymer

Aims: Chia seed (Salvia hispanica L.) gum is a mucoadhesive, biodegradable polymer with sustained release properties. Objective: The objective of this study was to compare different formulations of glipizide-loaded microparticles using chia seed mucilage and sodium alginate, focusing on sustained release and mucoadhesive properties. Background: The present study aimed to comparatively evaluate various eco-friendly formulations of glipizide-loaded microparticles prepared using chia seed mucilage and sodium alginate. Materials and Methods: Gum was extracted from chia seeds and lyophilized, and preformulation studies were performed according to established protocols. Microparticles were formulated using the ionic gelation method, with sodium alginate as a copolymer and zinc chloride as a cross-linking agent. The prepared microparticles were evaluated using scanning electron microscopy (SEM) for size and particle aggregation, and Fourier Transform infrared spectroscopy (FTIR) for drug-polymer interaction, entrapment efficiency, swelling index, and in vitro drug release. Results: The % yield of chia seed mucilage was 27.35%. The pH of the mucilaginous suspension was 4.67 ± 0.50. The moisture content value was 14.56 % ± 0.50. The values of Carr's index and Hausner's ratio were 22.58 ± 1.89 and 1.38 ± 0.05, respectively. FTIR spectra showed no interaction between pure glipizide and chia seed mucilage, confirming no possible change in glipizide's pharmacology. SEM studies have confirmed the shape of the microparticles to be spherical, with average sizes ranging from 1235.18 ± 8.7 to 1423.25 ± 9.5 µm, and the drug entrapment efficiency ranged from 64.25 ± 2.52 to 81.82 ± 7.56%. The release of glipizide from the microparticles was sustained, and the Higuchi and Korsmeyer-Peppas models were found to be the best-fit kinetic models. Conclusion: The promising copolymer blend of chia seed mucilage and sodium alginate was used for the development of sustained-release dosage forms. A copolymer blend with a ratio of 1:1 produced glipizide-loaded microparticles with sustained release profiles and good mucoadhesive ability, along with a high percentage of drug entrapment efficiency.

Development of gallic acid loaded composite nanovesicles for the topical treatment of acne: optimization, characterization, and clinical investigation

Gallic acid (GA) proved to produce desired effects topically in the treatment of acne, through its antibacterial, anti-inflammatory and antioxidant characteristics. In the current work, nanovesicular systems; aspasomes loaded with GA were prepared, and evaluated on in-vitro and ex-vivo levels. Formulations were coated with chitosan due to its mucoadhesive properties. Results indicated that the size of the formulations ranged between 273.20 and 855.00 nm, with positively charged zeta potential ranging between 30.60 and 34.40 mV, EE% ranging between 57.651% and 95.20% and good stability after 3-months storage. The formulae provided a sustained drug release of 98.22% over 24 h, 5.4-fold higher ex-vivo skin deposition compared to GA solution, and powerful antioxidant potential compared to the control solution and appeared as spherical bilayer vesicles on being examined using transmission electron microscope. A clinical study was carried out on patients suffering from acne, where the reduction percent of comedones, inflammatory, total acne lesions and infiltrate was calculated. Results revealed that aspasomes exhibited reduction percentages of 72.35%, 80.33%, 77.95% and 90.01% ± for comedones, inflammatory lesions, total lesions, and infiltrate, respectively compared to control solution providing an effective topical delivery system for the management of acne.

Role of In Vitro Tests in the Characterisation of Locally Applied, Locally Acting Drugs in the Throat: Application to Flurbiprofen.

Background/Objectives: For locally applied, locally acting generic drug products, comparison to an originator product based on systemic exposure is usually not feasible due to low plasma concentrations and inadequate reflection of local exposure at the site of action. Where a validated PD model exists, a comparative clinical study can be performed in healthy subjects; where no surrogate endpoint is available, patients with the relevant indication need to be enrolled, with all the associated factors which could result in lack of sensitivity. Even though the need for alternative in vitro approaches has been acknowledged by both industry and regulatory bodies, the complexity of in vivo drug delivery processes makes the development of guidance documents particularly difficult. Our objective was to present in vitro approaches less classically used and to address in vivo relevance of the selected tests. Methods: This article analyses current regulatory approaches in Europe and the U.S., and highlights the key advantages of in vitro tests in terms of their sensitivity, reliability, reproducibility and in vivo relevance using locally applied flurbiprofen in various formulations. Results: The in vitro esophageal retention (IVOR) model demonstrates that the first 6-10 min after application of different flurbiprofen formulations is important for their comparison and also offers the best correlation with in vivo data using the partial area under the concentration-time curves (pAUCs). Rheological evaluations further demonstrated that the mucoadhesive properties of the gel spray formulation are based on interaction with mucin. Conclusions: Designing a relevant in vitro test requires adequate evaluation of the complexity of the drug substance, drug product, dosing conditions and delivery processes.

Investigating the binding affinity, molecular dynamics, and ADMET properties of curcumin-IONPs as a mucoadhesive bioavailable oral treatment for iron deficiency anemia

Iron deficiency anemia (IDA) is a common health issue, and researchers are interested in overcoming it. Nanotechnology green synthesis is one of the recent approaches to making efficient drugs. In this study, we modeled curcumin-coated iron oxide nanoparticles (cur-IONPs) to study their predicted toxicity and drug-likeness properties, then to investigate mucoadhesive behavior by docking cur-IONPs with two main mucin proteins in gastrointestinal tract (GIT) mucosa (muc 5AC and muc 2). Furthermore, the stability of cur-IONPs/protein complexes was assessed by molecular dynamics. Our in-silico studies results showed that cur-IONPs were predicted to be potential candidates to treat IDA due to its mucoadhesive properties, which could enhance the bioavailability, time residency, and iron absorbance through GIT, in addition to its high safety profile with high drug-likeness properties and oral bioavailability. Finally, molecular dynamic simulation studies revealed stable complexes supporting strength docking studies. Our results focus on the high importance of in-silico drug design studies; however, they need to be supported with in vitro and in vivo studies to reveal the efficacy, toxicity, and bioavailability of cur-IONPs.

Quality by Design Approach to Nasal Mucoadhesive Microspheres: Enhanced Sumatriptan Succinate Delivery through Formulation and Characterization.

The primary therapeutic indications for sumatriptan succinate (STS) include the treatment of migraine and cluster headaches. To enhance mucoadhesion, sodium carboxymethyl cellulose (SCMC) and hydroxyl propyl methyl cellulose (HPMC K15M) were used in this study to develop nasal mucoadhesive microspheres of STS. A central composite design, facilitated by Design Expert software, was employed to assess the impact of polymer concentrations on mucoadhesion, involving nine different formulations. The study’s findings indicated that the microspheres were uniformly sized and spherical and that the polymers were compatible with STS. The optimal formulation, consisting of 220.711 mg of SCMC and 150 mg of HPMC K15M, demonstrated the highest level of mucoadhesion. This combination effectively regulated the discharge of STS from the mucoadhesive microspheres and significantly improved their mucoadhesive properties. These results suggest that the strategic use of SCMC and HPMC K15M can enhance the performance of nasal mucoadhesive microspheres, ensuring a controlled release of STS and improved adhesion to mucosal surfaces. This has the potential to optimize the therapeutic efficacy of STS in treating migraine and cluster headaches.

Mucoadhesive and drug release of cholic acid based thiomeric micelles and encapsulated silver and gold nanoparticles for anticancer studies

Among the various drug delivery system, mucoadhesive formulation is a promising approach to deliver drugs and vaccine through close contact with the absorption site and mucous membrane. Bile acids have received considerable interest in drug delivery (DD) applications owing to their advantages of biocompatibility, ability to act as both drug solubilizing and permeation-modifying agents. In this aspects, cholic acid (CA) based thiomeric micelles with improved mucoadhesive properties have been synthesized by functionalization of thiol groups and conjugation of PEG. The synthesized CA based thiomeric micelles (TCA-PEG) were characterized by 1HNMR, ATR-IR, GPC, Zeta potential and contact angle techniques. The critical micelle concentration (CMC) of TCA-PEG was measured by a fluorescence spectrometer using pyrene as a probe. The mucoadhesive properties of TCA-PEG polymeric micelles (PMs) were examined on the goat anterior tongue mucosa with an effectively higher adhesion of 40 % up to 3 h study period. Also, curcumin loaded TCA-PEG PMs showed only 13 % of the drug released up to the period of 3 h. The TCA-PEG PMs act as reducing and stabilizing agents for the preparation of gold and silver nanoparticle (Ag and Au NPs) and were characterized by UV–visible, DLS, Zeta potential, XPS, and HR-TEM techniques. The cytotoxicity and cellular apoptosis of TCA-PEG PMs encapsulated Ag and Au NPs were examined by MTT assay and AO/PI dual staining using MCF-7 breast cancer cells wherein AgNPs showed an effective cytotoxicity than AuNPs. The developed TCA-PEG PMs act as reservoir for soubilization of hydrophobic and hydrophilic drugs and ideal template for encapsulation of silver and gold nanoparticles for mucoadhesive DD system.

Tailoring copolymer architectures and macromolecular interactions for enhanced nanotherapeutic delivery: A design-by-architecture approach

Amphiphilic copolymers with precise macromolecular topologies are crucial in nanomedicine for enhancing drug delivery by improving solubilization, stabilization, and therapeutic efficacy on target tissues. This study employs a design-by-architecture approach to identify factors influencing interactions between synthesized macromolecules and biological systems for optimal drug nanodelivery. Copolymers combining poly(ε-caprolactone) blocks and poly(polyethylene glycol methacrylate) or poly(glycerol methacrylate), were synthesized to investigate how architectural adjustments impact self-assembly, nanoparticle size, drug loading, and biomolecule interactions. Linear and brush block copolymers with varied block lengths were studied for their self-assembly behavior in aqueous environments. Both copolymer types formed smaller nanoparticles with extended hydrophilic blocks, with brush block copolymers showing superior performance due to their peculiar macromolecular architecture. Incorporating ‘clickable’ glycidyl units within the hydrophilic block minimally affected particle size. Controlled functionalization with thiol groups resulted in stable nanoparticles with enhanced size reduction and mucoadhesive properties, potentially improving targeted drug delivery and therapeutic effects.

Review of Intranasal Active Pharmaceutical Ingredient Delivery Systems.

In recent decades, there has been an increased interest in the development of intranasal delivery systems for active pharmaceutical ingredients (APIs) not only for treating local nasal diseases but also for treating systemic diseases, central nervous system (CNS) disorders, and vaccine delivery. The nasal cavity possesses a unique set of anatomical characteristics for delivering active pharmaceutical ingredients, but there are several limitations that recent research in the field of the intranasal administration of APIs aims to overcome. For the effective delivery of nasal preparations, active pharmaceutical ingredients are incorporated into various micro- and nanosystems. Some of the most commonly encountered API delivery systems in the scientific literature include liposomal systems, polymer particles with mucoadhesive properties, in situ gels, nano- and microemulsions, and solid lipid particles. This article provides a review of research on the development of nasal preparations for treating local nasal cavity diseases (in particular, for antibiotic delivery), systemic diseases (analgesics, drugs for cardiovascular diseases, antiviral and antiemetic drugs), CNS disorders (Alzheimer's disease, Parkinson's disease, epilepsy, schizophrenia, depression), and vaccine delivery. The literature data show that active research is underway to reformulate drugs of various pharmacotherapeutic groups into a nasal form.

Optimization and evaluation of a chitosan-coated PLGA nanocarrier for mucosal delivery of Porphyromonas gingivalis antigens

Recent advances in understanding Alzheimer's disease (AD) suggest the possibility of an infectious etiology, with Porphyromonas gingivalis emerging as a prime suspect in contributing to AD. P. gingivalis may invade systemic circulation via weakened oral/intestinal barriers and then cross the blood-brain barrier (BBB), reaching the brain and precipitating AD pathology. Based on the proposed links between P. gingivalis and AD, a prospective approach is the development of an oral nanovaccine containing P. gingivalis antigens for mucosal delivery. Targeting the gut-associated lymphoid tissue (GALT), the nanovaccine may elicit both mucosal and systemic immunity, thereby hampering P. gingivalis ability to breach the oral/intestinal barriers and the BBB, respectively.The present study describes the optimization, characterization, and in vitro evaluation of a candidate chitosan-coated poly(lactic-co-glycolic acid) (PLGA-CS) nanovaccine containing a P. gingivalis antigen extract. The nanocarrier was prepared using the double emulsion solvent evaporation method and optimized for selected experimental factors, e.g. PLGA amount, surfactant concentration, w1/o phase ratio, applying a d-optimal statistical design to target the desired physicochemical criteria for its intended application. After nanocarrier optimization, the nanovaccine was characterized in terms of particle size, polydispersity index (PdI), ζ-potential, encapsulation efficiency (EE), drug loading (DL), morphology, and in vitro release profile, as well as for mucoadhesivity, stability under simulated gastrointestinal conditions, antigen integrity, in vitro cytotoxicity and uptake using THP-1 macrophages.The candidate PLGA-CS nanovaccine demonstrated appropriate physicochemical, mucoadhesive, and antigen release properties for oral delivery, along with acceptable levels of EE (55.3 ± 3.5 %) and DL (1.84 ± 0.12 %). The integrity of the encapsulated antigens remained uncompromised throughout NPs production and simulated gastrointestinal exposure, as confirmed by SDS-PAGE and Western blotting analyses. Furthermore, the nanovaccine showed effective in vitro uptake, while exhibiting low cytotoxicity. Taken together, these findings underscore the potential of PLGA-CS NPs as carriers for adequate antigen mucosal delivery, paving the way for further investigations into their applicability as vaccine candidates against P. gingivalis.