Acceptance of HPV vaccination in boys among mothers from selected churches in Accra, Ghana.

BACKGROUND: Almost all cases of cervical and anal cancer have been linked to the human papillomavirus (HPV). However, in addition to women who develop HPV-related cervical cancer, both men and women can also develop cancers of the anus, oral cavity, and oropharynx that are attributed to HPV. However, literature on HPV vaccination among boys globally, in Africa, and most especially in Ghana is scarce. Thus, the main objective of this study was to explore the acceptance of HPV vaccination in boys among mothers from selected churches in Accra, Ghana. METHODS: In this study, a qualitative exploratory design was utilized to enlist 30 mothers who have male children aged between 9 and 12 years from the Greater Accra Region of Ghana. The recruitment of participants was carried out using a purposive sampling technique, and they were subsequently interviewed in-depth in a face-to-face setting, with the entire conversation being recorded for reference. After transcription, the recorded data were analyzed through content analysis. FINDINGS: Upon analyzing the data, two (2) primary themes and 11 sub-themes emerged. The research showed that although the majority of the mothers were unaware of HPV in boys, they perceived it as a positive initiative and expressed a willingness to allow their sons to receive the vaccine. However, some participants mentioned certain factors that they believed could hinder the acceptance of HPV vaccination in boys among mothers. These included concerns about injection-related pain, high cost, and fears that the vaccine could make men immoral or infertile. CONCLUSION: The study revealed poor awareness of HPV vaccination in boys among mothers, and hence, suggested the need to increase the awareness on HPV vaccination in boys among mothers as well as the public to increase its acceptance.

Toll-like Receptor-4 (TLR4) Agonist-Based Intranasal Nanovaccine Delivery System for Inducing Systemic and Mucosal Immunity.

Eliciting a robust immune response at mucosal sites is critical in preventing the entry of mucosal pathogens such as influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This task is challenging to achieve without the inclusion of a strong and safe mucosal adjuvant. Previously, inulin acetate (InAc), a plant-based polymer, is shown to activate toll-like receptor-4 (TLR4) and elicit a robust systemic immune response as a vaccine adjuvant. This study investigates the potential of nanoparticles prepared with InAc (InAc-NPs) as an intranasal vaccine delivery system to generate both mucosal and systemic immune responses. InAc-NPs (∼250 nm in diameter) activated wild-type (WT) macrophages but failed to activate macrophages from TLR4 knockout mice or WT macrophages when pretreated with a TLR4 antagonist (lipopolysaccharide-RS (LPS-RS)), which indicates the selective nature of a InAc-based nanodelivery system as a TLR4 agonist. Intranasal immunization using antigen-loaded InAc-NPs generated ∼65-fold and 19-fold higher serum IgG1 and IgG2a titers against the antigen, respectively, as compared to PLGA-NPs as a delivery system. InAc-NPs have also stimulated the secretion of sIgA at various mucosal sites, including nasal-associated lymphoid tissues (NALTs), lungs, and intestine, and produced a strong memory response indicative of both humoral and cellular immune activation. Overall, by stimulating both systemic and mucosal immunity, InAc-NPs laid a basis for a potential intranasal delivery system for mucosal vaccination.

Targeted Protein-Specific Multi-Epitope-Based Vaccine Designing against Human Cytomegalovirus by Using Immunoinformatics Approaches.

Cytomegaloviruses are emerging pathogenic agents known to cause congenital disorders in humans. In this study, immune epitopes (CTL, B cell and HTL) were screened for highly antigenic target proteins of the Human Cytomegalovirus. These shortlisted epitopes were then joined together through suitable linkers to construct multi epitope-based vaccine constructs (MEVCs). The functionality of each vaccine construct was evaluated through tertiary vaccine structure modelling and validations. Furthermore, physio-chemical properties including allergenicity, antigenicity molecular weight and many others were also predicted. The vaccine designs were also docked with the human TLR-4 receptor to demonstrate the receptor specific affinity and formed interactions. The vaccine peptides sequences were also subjected to codon optimization to confirm the potential vaccines expression in E. coli hosts. Additionally, all the MEVCs were also evaluated for immune response (IgG and IgM) induction. However, further in vivo tests are needed to ensure the efficacy of these vaccine designs.

Induction of Innate and Adaptive Immune Response against Recombinant HBsAg Protein Entrapped in Docosahexaenoic Acid Nanovesicles through Biomarkers.

The present study focused on demonstrating the induction of humoral and cell-mediated immunity through the establishment of a cytokine network. We hypothesized the anti-inflammatory, pro-inflammatory, and IgE antibody levels after vaccination with lyophilized recombinant HBsAg-loaded docosahexaenoic acid nanovesicles (LRPDNV), and the efficacy compared well with standard commercial recombinant hepatitis B vaccine. The cytokine network was efficiently regulated by striking a balance between pro-inflammatory cytokines IL-6, IL-8R, and IL-12 and anti-inflammatory cytokines such as IL-2, IL-4, IL-10, and IFN-γ immune response on the 14th and 30th day after primary and booster immunization. The acute phase protein CRP level was increased due to IL-6 after immunizing with LRPDNV. On the other hand, the IgE level was not significantly increased to induce any allergic reactions after immunization with LRPDNV. The study concluded that after immunizing with LRPDNV, a significant immunological response was established, implying that DHA nanovesicles have significant potential as an adjuvant method for delivering recombinant HBsAg protein. On the other hand, following immunization with LRPDNV, the IgE level was not noticeably elevated enough to cause any adverse reactions. The study concludes that a robust immune response was developed after immunizing with LRPDNV and suggests that DHA nanovesicles have much potential to deliver recombinant HBsAg protein.

Design and characterization of Lactotransferrin peptide-loaded dextran-docosahexaenoic acid nanoparticles: an immune modulator for hepatic damage.

The primary objective of this research was to create injectable delivery formulations using Lactotransferrin (LTF) peptide-loaded dextran nanoparticles coated with docosahexaenoic acid. These nanoparticles, designated as LLDDNP, underwent a lyophilization process. The study encompassed a comprehensive investigation, including physicochemical characterization, in vivo assessment of biomarkers, and an examination of immune response through cytokine modulation. The zeta potential of LLDDNP was - 24.5 ± 12 mV, while their average particle size was 334.9 z.d.nm. The particles exhibited a conductivity of 2.10 mS/cm, while their mobility in the injectable dosage form was measured at - 3.65 µm cm/Vs. The scanning electron microscopy investigation, the lyophilization processes resulted in discrete particles forming particle aggregations. However, transmission electron microscopy analysis revealed that LLDDNP is spherical and smooth. The thermogram showed that about 95% of LLDDNP's weight was lost at 270 °C, indicating that the particles are extremely thermal stable. The XRD analysis of LLDDNP exhibited clear and distinctive peaks at 2θ angles, specifically at 9.6°, 20.3°, 21.1°, 22°, 24.6°, 25.2°, 36°, and 44.08°, providing compelling evidence of the crystalline nature of the particles. According to proton NMR studies, the proton dimension fingerprint region of LLDDNP ranges from 1.00 to 1.03 ppm. The in vitro release of LTF from LLDDNP was found to follow zero-order kinetics, with a commendable R2 value of 0.942, indicating a consistent and predictable release pattern over time. The in vivo investigation revealed a significant impact of hepatotoxicity on the elevation of various cytokines, including IL-1ß, IL-6, IL-8R, TNF-α, IL-2, IL-4, IL-10, and IFN-γ. Additionally, the presence of hepatotoxicity led to an increase in apoptosis markers, namely caspase 3 and caspase 9, as well as elevated levels of liver biomarkers such as CRP, ALP, ALT, and AST. In contrast, the treatment with LLDDNP modulated the levels of all biomarkers, including cytokines level in the treatment group extremely high significant at p < 0.001.

Preparation and In Vitro Evaluation of Levofloxacin-Loaded Floating Tables Using Various Rate-Controlling Agents.

Floating tablets are a new approach to extending the time a drug is in the stomach to improve therapy outcomes. Floating tablets were formulated with the drug, the polymers hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC), and starch, fillers, and lubricants. The tablets were prepared using the direction compression method. The tablets' physical quality control tests were found to be within acceptable limits. The tablets extended drug release up to 12 h and were uniform in their drug contents. The swelling index of the tablets ranged from 60 ± 0.11 to 66 ± 0.14%, and the tablets were less dense than water. The floating lag time (10 ± 0.23 to 16 ± 0.09 s) and total floating time (>12 h) showed good floating behaviors. The kinetic modeling showed that the drug was released from the tablets by pseudo-diffusion, swelling, erosion, or anomalous non-Fickian diffusion. F6 (starch and CMC) showed higher n values (0.994 ± 0.04), exhibiting pseudo-zero-order drug release kinetics compared to those of other tablets. The dissolution data of the test and reference tables were not similar (P > 0.05). In terms of antimicrobial activity, the zones of inhibition of the test F6 tablet powders (5.3 ± 0.08 mm) and the reference tablet powders (5.9 ± 0.13 mm) were found to be significantly similar (P > 0.05). The study concluded that these floating tablets can improve the gastric residence time and therapeutic outcomes.

Utilization of experimental design in the formulation and optimization of hyaluronic acid-based nanoemulgel loaded with a turmeric-curry leaf oil nanoemulsion for gingivitis.

Numerous problems affect oral health, and intensive research is focused on essential oil-based nanoemulsions that might treat prevent or these problems. Nanoemulsions are delivery systems that enhance the distribution and solubility of lipid medications to targeted locations. Turmeric (Tur)- and curry leaf oil (CrO)-based nanoemulsions (CrO-Tur-self-nanoemulsifying drug delivery systems [SNEDDS]) were developed with the goal of improving oral health and preventing or treating gingivitis. They could be valuable because of their antibacterial and anti-inflammatory capabilities. CrO-Tur-SNEDDS formulations were produced using the response surface Box-Behnken design with different concentrations of CrO (120, 180, and 250 mg), Tur (20, 35, and 50 mg), and Smix 2:1 (400, 500, and 600 mg). The optimized formulation had a bacterial growth inhibition zone of up to 20 mm, droplet size of less than 140 nm, drug-loading efficiency of 93%, and IL-6 serum levels of between 950 ± 10 and 3000 ± 25 U/ml. The optimal formulation, which contained 240 mg of CrO, 42.5 mg of Tur, and 600 mg of Smix 2:1, was created using the acceptable design. Additionally, the best CrO-Tur-SNEDDS formulation was incorporated into a hyaluronic acid gel, and thereafter it had improved ex-vivo transbuccal permeability, sustained in-vitro release of Tur, and large bacterial growth suppression zones. The optimal formulation loaded into an emulgel had lower levels of IL-6 in the serum than the other formulations evaluated in rats. Therefore, this investigation showed that a CrO-Tur-SNEDDS could provide strong protection against gingivitis caused by microbial infections.

Formulation development of lipid polymer hybrid nanoparticles of doxorubicin and its in-vitro, in-vivo and computational evaluation.

The purpose of this study was to assess the parameters of doxorubicin (DOX) loaded lipid polymer hybrid nanoparticles (LPHNs) formulation development, and then the bioavailability of DOX were determined in the rabbit model, in order to evaluate the intrinsic outcome of dosage form improvement after the oral administration. LPHNs were prepared by combine approach, using both magnetic stirring and probe sonication followed by its characterization in terms of size-distribution (Zeta Size), entrapment efficiency (EE), loading capacity, and the kinetics of DOX. LPHNPs were further characterized by using scanning electron microscopy (SEM), powder X-Ray diffractometry (P-XRD), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), in vitro and in vivo studies. The molecular modeling was determined through the density functional theory (DFT) simulations and interactions. DOX loaded and unloaded LPHNs were administered orally to the rabbits for bioavailability and pharmacokinetic parameters determinations. The plasma concentration of DOX was determined through high performance liquid chromatography (HPLC). The average size of DOX-loaded LPHNs was 121.90 ± 3.0 nm. The drug loading of DOX was 0.391% ± 0.01 of aqueous dispersion, where its encapsulation efficiency was 95.5% ± 1.39. After oral administration of the DOX-LPHNs, the area under the plasma drug concentration-time curve (AUC) improved about 2-folds comparatively (p < 0.05). DFT simulations were used to understand the interactions of polymers with different sites of DOX molecule. The larger negative binding energies (-9.33 to -18.53 kcal/mol) of the different complexes evince that the polymers have stronger affinity to bind with the DOX molecule while the negative values shows that the process is spontaneous, and the synthesis of DOX-LPHNs is energetically favorable. It was concluded that DOX-LPHNs provides a promising new formulation that can enhance the oral bioavailability, which have optimized compatibilities and improve the pharmacokinetic of DOX after oral administration.

Production, Characterization, and In Vitro and In Vivo Studies of Nanoemulsions Containing St. John's Wort Plant Constituents and Their Potential for the Treatment of Depression.

The current project was designed to prepare an oil-in-water (oil/water) hypericin nanoemulsion using eucalyptus oil for the preparation of an oil phase with chitosan as an emulsion stabilizer. The study might be a novelty in the field of pharmaceutical sciences, especially in the area of formulation development. Tween® 80 (Polysorbate) was used as the nonionic surfactant. The nanoemulsion was prepared by using the homogenization technique, followed by its physicochemical evaluation. The surface morphological studies showed the globular structure has a nano-sized diameter, as confirmed by zeta size analysis. The zeta potential analysis confirmed a positive surface charge that might be caused by the presence of chitosan in the formulation. The pH was in the range of 5.14 to 6.11, which could also be compatible with the range of nasal pH. The viscosity of the formulations was found to be affected by the concentration of chitosan (F1-11.61 to F4-49.28). The drug release studies showed that the presence of chitosan greatly influenced the drug release, as it was noticed that formulations having an elevated concentration of chitosan release lesser amounts of the drug. The persistent stress in the mouse model caused a variety of depressive- and anxiety-like behaviors that can be counteracted by chemicals isolated from plants, such as sulforaphane and tea polyphenols. In the behavioral test and source performance test, hypericin exhibited antidepressant-like effects. The results show that the mice treated for chronic mild stress had a considerably higher preference for sucrose after receiving continuous hypericin for 4 days (p = 0.0001) compared to the animals administered with normal saline (p ≤ 0.0001) as well as the naïve group (p ≤ 0.0001). In conclusion, prepared formulations were found to be stable and can be used as a potential candidate for the treatment of depression.

Characterization of cisplatin-loaded chitosan nanoparticles and rituximab-linked surfaces as target-specific injectable nano-formulations for combating cancer.

The present study was carried out to develop cisplatin-loaded chitosan nanoparticles (CCNP) and cisplatin-loaded chitosan nanoparticle surface linked to rituximab (mAbCCNP) as targeted delivery formulations. The two formulations (CCNP and mAbCCNP) exhibited significant physicochemical properties. The zetapotential (ZP) values of CCNP and mAbCCNP were 30.50 ± 5.64 and 26.90 ± 9.09 mV, respectively; while their particle sizes were 308.10 ± 1.10 and 349.40 ± 3.20 z.d.nm, respectively. The poly dispersity index (PDI) of CCNP was 0.257 ± 0.030 (66.6% PDI), while that of mAbCCNP was 0.444 ± 0.007 (57.60% PDI). Differential scanning calorimetry (DSC) revealed that CCNP had endothermic peaks at temperatures ranging from 135.50 to 157.69 °C. A sharp exothermic peak was observed at 95.79 °C, and an endothermic peak was observed at 166.60 °C. The XRD study on CCNP and mAbCCNP revealed distinct peaks at 2θ. Four peaks at 35.38°, 37.47°, 49.29°, and 59.94° corresponded to CCNP, while three distinct peaks at 36.6°, 49.12°, and 55.08° corresponded to mAbCCNP. The in vitro release of cisplatin from nanoparticles followed zero order kinetics in both CCNP and mAbCCNP. The profile for CCNP showed 43.80% release of cisplatin in 6 h (R2 = 0.9322), indicating linearity of release with minimal deviation. However, the release profile of mAbCCNP showed 22.52% release in 4 h (R2 = 0.9416), indicating linearity with sustained release. In vitro cytotoxicity studies on MCF-7 ATCC human breast cancer cell line showed that CCNP exerted good cytotoxicity, with IC50 of 4.085 ± 0.065 µg/mL. However, mAbCCNP did not elicit any cytotoxic effect. At a dose of 4.00 µg/mL cisplatin induced early apoptosis and late apoptosis, chromatin condensation, while it produced secondary necrosis at a dose of 8.00 µg/mL. Potential delivery system for cisplatin CCNP and mAbCCNP were successfully formulated. The results indicated that CCNP was a more successful formulation than mAbCCNP due to lack of specificity of rituximab against MCF-7 ATCC human breast cancer cells.

Design, Characterization, and Immune Augmentation of Docosahexaenoic Acid Nanovesicles as a Potential Delivery System for Recombinant HBsAg Protein.

Recombinant HBsAg-loaded docosahexaenoic acid nanovesicles were successfully developed, lyophilized (LRPDNV) and characterized for their physico-chemical properties. The zetapotential (ZP) of LRPDNV was -60.4 ± 10.4 mV, and its polydispersity (PDI) was 0.201, with a % PDI of 74.8. The particle sizes of LRPDNV were 361.4 ± 48.24 z. d.nm and 298.8 ± 13.4 r.nm. The % mass (r.nm) of LRPDNV in a colloidal injectable system was 50, its mobility value was -3.417 µm cm/Vs, while the conductivity of the particles was 0.728 (mS/cm). Transmission electron microscopic (TEM) analysis showed smooth morphological characteristics of discrete spherical LRPDNV. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) of LRPDNV revealed that LRPDNV is thermostable. The X-ray diffraction (XRD) studies showed a discrete crystalline structure of LRPDNV at 2θ. Nuclear magnet resonance (NMR) studies (1H-NMR and 13C-NMR spectrum showed the discrete structure of LRPDNV. The immunogenicity study was performed by antibody induction technique. The anti-HBs IgG levels were elevated in Wistar rats; the antibody induction was observed more in the product (LRPDNV) treatment group when compared to the standard vaccine group. The level of antibodies on the 14th and 30th day was 6.3 ± 0.78 U/mL and 9.24 ± 1.76 U/mL in the treatment and standard vaccine groups, respectively. Furthermore, the antibody level on the 30th day in the treatment group was 26.66 ± 0.77 U/mL, and in the standard vaccine group, the antibody level was 23.94 ± 1.62 U/mL. The LRPDNV vaccine delivery method released HBsAg sustainably from the 14th to the 30th day. The results of this study indicate the successful formulation of DHA nanovesicles which have great potential as an adjuvant system for the delivery of recombinant HBsAg protein.

Formulation and evaluation of injectable dextran sulfate sodium nanoparticles as a potent antibacterial agent.

The purpose of this study was to develop a novel nano antibacterial formulation of dextran sulfate sodium polymer. The dextran sulfate sodium (DSS) nanoparticles were formulated with gelation technique. The nanoparticles exhibited significant physicochemical and effective antibacterial properties, with zeta potential of - 35.2 mV, particle size of 69.3 z d nm, polydispersity index of 0.6, and percentage polydispersity of 77.8. The DSS nanoparticles were stable up to 102 °C. Differential scanning calorimetry revealed an endothermic peak at 165.77 °C in 12.46 min, while XRD analysis at 2θ depicted various peaks at 21.56°, 33.37°, 38.73°, 47.17°, 52.96°, and 58.42°, indicating discrete nanoparticle formation. Antibacterial studies showed that the DSS nanoparticles were effective against Gram-positive and Gram-negative bacteria. The minimum inhibitory concentrations of DSS nanoparticles for Bacillus subtilis (B. subtilis), Staphylococcus aureus (S. aureus), Streptococcus pyogenes (S. pyogenes), Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Klebsiella pneumoniae (K. pneumoniae) and Proteus vulgaris (P. vulgaris) were 150, 200, 250, 150, 200, 250, 250 µg/mL, respectively. The antibacterial effects of DSS nanoparticles were in the order E. coli (26 ± 1.2 mm) at 150 µg/mL > S. pyogenes (24.6 ± 0.8 mm) at 250 µg/mL > B. subtilis (23.5 ± 2 mm) at 150 µg/mL > K. pneumoniae (22 ± 2 mm) at 250 µg/mL > P. aeruginosa (21.8 ± 1 mm) at 200 µg/mL > S. aureus (20.8 ± 1 mm) at 200 µg/mL > P. vulgaris (20.5 ± 0.9 mm) at 250 µg/mL. These results demonstrate the antibacterial potency of DSS injectable nanoparticles.

Site-directed non-covalent polymer-drug complexes for inflammatory bowel disease (IBD): Formulation development, characterization and pharmacological evaluation.

Inflammatory Bowel Diseases (IBD) is a debilitating condition that affects ~70,000 new people every year and has been described as "an expensive disease with no known cure". In addition, IBD increases the risk of developing colon cancer. The current therapeutics for IBD focus on the established disease where the immune dysfunction and bowel damage have already occurred but do not prevent or delay the progression. The current work describes a polymer-based anti-inflammatory technology (Ora-Curcumin-S) specifically targeted to the luminal side of the colon for preventing and/or treating IBD. Ora-Curcumin-S was prepared by molecular complexation of curcumin with a hydrophilic polymer Eudragit® S100 using co-precipitation method. Curcumin interacted with the polymer non-covalently and existed in an amorphous state as demonstrated by various physicochemical techniques. Ora-Curcumin-S is a polymer-drug complex, which is different than solid dispersions in that the interactions are retained even after dissolving in aqueous buffers. Ora-Curcumin-S was >1000 times water soluble than curcumin and importantly, the enhanced solubility was pH-dependent, which was observed only at pHs above 6.8. In addition, around 90% of Ora-Curcumin-S was stable in phosphate buffer, pH 7.4 and simulated intestinal fluid after 24 h, in contrast to 10-20% unformulated curcumin. Ora-Curcumin-S inhibited Monophosphoryl Lipid-A and E. coli induced inflammatory responses in dendritic cells and cells over expressing Toll-Like Receptor-4 (TLR-4) suggesting that Ora-Curcumin-S is a novel polymer-based TLR-4 antagonist. Preliminary pharmacokinetics in mice showed targeted delivery of soluble curcumin to the colon lumen without exposing to the systemic circulation. Furthermore, Ora-Curcumin-S significantly prevented colitis and associated injury in a mouse model of ulcerative colitis estimated using multiple preclinical parameters: colonoscopy pictures, body weight, colon length, colon edema, spleen weight, pro-inflammatory signaling and independent pathological scoring. Overall, the outcome of this innovative proof-of-concept study provides an exciting and locally-targeted pathway for a dietary therapeutic option for IBD patients to help limit colonic inflammation and thus susceptibility to colitis-associated colorectal cancer.

Pathogen-mimicking vaccine delivery system designed with a bioactive polymer (inulin acetate) for robust humoral and cellular immune responses.

New and improved vaccines are needed against challenging diseases such as malaria, tuberculosis, Ebola, influenza, AIDS, and cancer. The majority of existing vaccine adjuvants lack the ability to significantly stimulate the cellular immune response, which is required to prevent the aforementioned diseases. This study designed a novel particulate based pathogen-mimicking vaccine delivery system (PMVDS) to target antigen-presenting-cells (APCs) such as dendritic cells. The uniqueness of PMVDS is that the polymer used to prepare the delivery system, Inulin Acetate (InAc), activates the innate immune system. InAc was synthesized from the plant polysaccharide, inulin. PMVDS provided improved and persistent antigen delivery to APCs as an efficient vaccine delivery system, and simultaneously, activated Toll-Like Receptor-4 (TLR-4) on APCs to release chemokine's/cytokines as an immune-adjuvant. Through this dual mechanism, PMVDS robustly stimulated both the humoral (>32 times of IgG1 levels vs alum) and the cell-mediated immune responses against the encapsulated antigen (ovalbumin) in mice. More importantly, PMVDS stimulated both cytotoxic T cells and natural killer cells of cell-mediated immunity to provide tumor (B16-ova-Melanoma) protection in around 40% of vaccinated mice and significantly delayed tumor progression in rest of the mice. PMVDS is a unique bio-active vaccine delivery technology with broader applications for vaccines against cancer and several intracellular pathogens, where both humoral and cellular immune responses are desired.