Sublingual Tissue Research Articles

Effects of Glucose Intolerance on Physiological Accumulation in Salivary Glands and Palatine Tonsils During 18F-Fluorodeoxyglucose Positron Emission Tomography.

We evaluated the effects of chronic hyperglycemia on physiological accumulation in salivary glands and tonsils during18F-fluorodeoxyglucose positron emission tomography (FDG-PET/CT). 12,738 patients underwent whole-body FDG-PET/CT in our institute during the study period. Of these, the case group comprised 777 patients with a blood glucose (BG) level >140 mg/dL; the control group comprised an equal number of randomly selected age- and sex-matched individuals with a BG level <110 mg/dL. Within the case group, the diabetic subgroup was defined as individuals with a BG level >200 mg/dL. Visual assessment and accumulation intensity among tissues were compared between the case and control groups, including (1) the mean difference in maximum standardized uptake value (SUVmax), (2) the difference in the proportion of patients with visible tissues on maximum intensity projection images, and (3) differences between the diabetic subgroup and the control group. Parotid, submandibular, sublingual, and tonsillar tissues all showed significantly lower SUVmax in the case group than in the control group. The proportions of individuals with visible uptake in the parotid and tonsillar tissues and in the sublingual gland were significantly smaller in the case group than in the control group. Tonsillar uptake was observed in more than 90% of individuals in the control group but in two-thirds of patients in the diabetic subgroup. Accumulation in the parotid and submandibular glands was visible in approximately 80% of individuals in the control groupbut only half of patients in the diabetic subgroup. Physiological accumulation in salivary glands and tonsils is significantly reduced among individuals with hyperglycemia or diabetes.

Alteration of Sublingual Gland after Exposure to 6-Mercaptopurine in Male Rat: Potential Efficacy of Propolis

Objective: Chemotherapeutic drugs not only have a therapeutic effect, but also cause serious damage to healthy organs. In this study, we investigated on the possible efficacy of propolis (PS) on the sublingual gland tissues exposed to 6-mercaptopurine (6MR) in male rats. Materials and Methods: Twenty-eight Wistar albino rats were allocated to four groups: control (KON), PS, 6MR, 6MR+PS. At 12 days of trial, sublingual glands of all rats were immediately dissected and analysed using the stereological technique and histological examination. Results: Our findings revealed a significant increase in the total volume of stroma and significant decrease in the total volume of the total volumes of mucous acini, straited ducts, interlobular ducts, and intralobular ducts in the 6MR group than the KON group (p&amp;lt;0.05). A significant decrease was also found in the mucous cell number and the serous cell number in the 6MR group than the KON group (p&amp;lt;0.05). In the 6MR+PS group, we observed that the total volume of stroma, as well as the mucous cell number and the serous cell number were increased compared to the 6MR group (p&amp;lt;0.05). Besides, the total volumes of mucous acini, straited ducts, interlobular ducts, and intralobular ducts were significantly increased in the 6MR+PS group than the 6MR group (p&amp;lt;0.05). Conclusion: Our results showed that 6MR treatment caused toxicity in sublingual gland tissues, as well as PS application improved such changes in sublingual glands exposed to 6MR.

Reconstructive strategies following surgical resection of malignant sublingual gland tumors: A single institution experience

ObjectiveTo investigate the characteristics and treatment modalities of malignant tumors originating from the sublingual gland, as well as evaluate the therapeutic outcomes following free flap reconstruction. MethodsA retrospective statistical analysis was conducted on the clinical data of nine patients diagnosed with malignant neoplasms tumor of the sublingual gland. ResultsNine case of malignant tumors originated from the sublingual glandular tissue, encompassing eight adenoid cystic carcinoma (ACC) and a single case of bipartite differentiated carcinoma—a hybrid of epithelial-myoepithelial carcinoma and adenoid cystic carcinoma. Among the nine patients, four anterolateral thigh flaps were used (three of which were thin flaps), and five forearm flaps were also empoyed. The size of flaps varied, with the lengths ranging from 4 cm to 9 cm, and the widths ranging from 2.5 cm to 6 cm. The vessels chosen for anastomosis were the superior thyroid artery in seven cases, the facial artery in one case, and the lingual artery in one case. Among the eight patients who underwent dissection of cervical lymph nodes, metastasis were found in one case. Two patients underwent adjuvant radiotherapy. Upon postoperative follow-up, there was no recurrence in any of the nine patients . ConclusionThe anterolateral thigh perforator flap thinning technique can be employed for postoperative reconstruction of malignant sublingual gland tumors.

Immunohistological profiling confirms salivary gland-like nature of the tubarial glands and suggests closest resemblance to the palatal salivary glands

Background and purposeHigh label uptake in 68 Ga-PSMA-11 PET/CT recently identified a bilateral nasopharyngeal structure as a salivary gland (SG)-like additional ‘area of interest’, to be considered in conditions affecting SGs. These structures were termed ‘tubarial glands’. We aimed to further characterize their histological and immunohistochemical position compared to established SGs. MethodsTubarial gland tissue was compared with parotid, submandibular, sublingual, palatal and labial SGs tissue using immunohistological techniques. ResultsExpression of acinar cell-associated aquaporin-5 (AQP5) was detected in tubarial glands, in an apical location associated in control, established SGs with polarized, secretory acinar cells. Keratin14 (KRT14) expression in cells peripheral to AQP5+ clusters also suggested presence of myoepithelial cells. α-amylase, prolactin-induced protein, proline rich protein Haelll subfamily 2, and Muc5B expression suggests mucous acinar cell presence, and presence of muco-serous acinar cells peripheral to putative mucous acinar cells. Expression of adrenergic receptor-β1 by acinar-like cells of the tubarial gland suggests ability to transduce sympathetic neuronal signaling. In terms of ductal architecture, tubarial glands contained large excretory-like ducts (similar to all other SGs), and squamous ducts, comprised of intermingled KRT14+ and KRT7+ cells. These squamous ducts were also observed in palatal, sublingual and labial SGs. No striated or intercalated ducts were observed, similar to palatal SGs. ConclusionBased on histological and immunohistochemical analyses, the tubarial glands resemble SGs. They most convincingly echo characteristics of the palatal SGs in terms of ductal cells, and both the palatal and labial SGs when considering acinar cells.

The "sand watch" mandible.

The lingual surface of the mandible's body is commonly indicated as presenting the submandibular and sublingual fossae, which are separated by the mylohyoid line. The mylohyoid line attaches to the mylohyoid muscle (MM). Less attention has been paid to the 'mylohyoid boutonnières', which allow the 'sublingual buttons' to pass through the mylohyoid muscle in the submandibular space. The cone-beam computed tomography files of patients were routinely examined for anatomical studies. Two cases were found with unexpected morphologies of the mandible's body - the mylohyoid lines were incomplete anteriorly, and herniated sublingual tissue determined an additional fossa inferior to that line in the premolar region. That fossa was termed the 'accessory submandibular fossa'. It determined on coronal slices a 'sand watch' contour of the mandible's body. With such a peculiar morphology, the mandible is more prone to fracture. Moreover, when inserting endosseous implants, the procedure should be carefully personalised in such rare cases.

Analysis of the sublingual artery using contrast-enhanced computed tomography.

This in vivo study aimed to clarify the position of the sublingual artery (SLA) relative to the mandibular bone and to infer the potential risk for injury during dental implant surgery. Contrast-enhanced computed tomography images of the mouth of 50 edentulous patients (100 sides) treated at Tokushima University Hospital were reviewed. Curved planar reconstructed images perpendicular to the alveolar ridge were processed and classified into molar, premolar, canine, and incisor regions. The SLA and its branches were identified, and the distance from the mandible to the SLA was measured. The SLA was located close to the mandible (<2 mm) in the molar, premolar, canine, and incisor segments in 12.0% (95% confidence interval 5.6%-18.4%), 20.6% (12.6%-28.7%), 30.5% (21.3%-39.8%), and 41.8% (28.8%-54.9%) cases, respectively. The SLA was located within ±3 mm craniocaudally to the upper wall of the mandibular canal in the molar and premolar regions in 50% of cases and within ±5 mm craniocaudally to the mylohyoid ridge in the canine and incisor regions in the other cases, with no sex or age-related differences. The vertical distance from the alveolar ridge to the SLA was influenced by sex and age owing to alveolar resorption, indicating that the alveolar ridge is not a reliable reference for predicting SLA position. As the risk of SLA injury always exist during dental implant placement and there is no way to confirm the SLA pathways in a patient, clinicians must avoid injuring the sublingual soft tissue.

Evaluation of the impact of blood donation on tissue perfusion and sublingual microcirculation in dogs: A pilot study

The objective was to assess the feasibility of the sublingual microcirculation evaluation in dogs by using Sidestream Dark Field (SDF) imaging device and to evaluate the impact of blood donation on sublingual microcirculation and tissue perfusion. Before and after blood sampling, macrocirculatory parameters and tissue perfusion parameters were collected. After quality assessment, four videos per individual and per period were retained for analysis. Data were presented as median (1st quartile – 3rd quartile).The evaluation of the sublingual microcirculation with SDF was feasible in sedated dogs: good quality videos could be recorded in 10/12 dogs (83%). The median blood donation volume was 14 mL/kg (13–15). A significant association between the volume of blood collected and the increase in heart rate was observed: for each milliliter of blood drawn, heart rate increased by 1 bpm (CI95% = [0.2, 2], P = 0.03). Blood collection was associated with a significant increase of shock index (estimate = 0.17, CI95% = [0.02, 0.32], P = 0.04). After blood donation, lactate concentration significantly decreased (before: 2.1 (1.7–2.8), after: 1.1 (0.8–1.7) mmol/l, P = 0.009). No significant variation of the microcirculatory parameters was observed.In conclusion, sublingual evaluation of the microcirculation with SDF technology is feasible in dogs. In the present condition, blood donation did not significantly alter microcirculation. These results need to be confirmed in a larger population.

CORNELIA DE LANGE SYNDROME IN A CHILD ASSOCIATED WITH RIGA-FEDE ULCER: CASE REPORT

Cornelia de Lange (CdLs) is a rare syndrome with multisystemic manifestations and frequent dental problems that can include the presence of micrognathia, delayed eruption, dental erosion, and self-mutilation of the tongue. A female patient, 2 years and 4 months old, attended a dental clinic for patients with special needs, with CdLs, with traumatic injury on the ventral surface of the tongue known as Riga-Fede ulcer, associated with the eruption of teeth 71 and 81. Examination of the oral mucous membranes showed a hyperplastic, pediculated, ulcerated lesion on the ventral tongue, and the diagnostic hypothesis of the injury was Riga-Fede disease. Due to the large hyperplasia of the sublingual tissue and the presence of hardened edges, an excisional biopsy of the lesion was planned, with the objective of performing differential diagnosis of the wound. Removal of the lesion resulted in improvements in the patient's diet and irritability and quality of life.

Investigating spectroscopic measurement of sublingual veins and tissue to estimate central venous oxygen saturation.

Venous oxygen saturation reflects venous oxygenation status and can be used to assess treatment and prognosis in critically ill patients. A novel method that can measure central venous oxygen saturation (ScvO2) non-invasively may be beneficial and has the potential to change the management routine of critically ill patients. The study aims to evaluate the potential of sublingual venous oxygen saturation (SsvO2) to be used in the estimation of ScvO2. We have developed two different approaches to calculate SsvO2. In the first one, near-infrared spectroscopy (NIRS) measurements were performed directly on the sublingual veins. In the second approach, NIRS spectra were acquired from the sublingual tissue apart from the sublingual veins, and arterial oxygen saturation was measured using a pulse oximeter on the fingertip. Twenty-six healthy subjects were included in the study. In the first and second approaches, average SsvO2 values were 75.0% ± 1.8 and 75.8% ± 2.1, respectively. The results of the two different approaches were close to each other and similar to ScvO2 of healthy persons (> 70%). Oxygen saturation of sublingual veins has the potential to be used in intensive care units, non-invasively and in real-time, to estimate ScvO2.

Coronary microvascular dysfunction is common in patients hospitalized with COVID-19 infection.

Background and AimsMicrovascular disease is considered as one of the main drivers of morbidity and mortality in severe COVID‐19, and microvascular dysfunction has been demonstrated in the subcutaneous and sublingual tissues in COVID‐19 patients. The presence of coronary microvascular dysfunction (CMD) has also been hypothesized, but direct evidence demonstrating CMD in COVID‐19 patients is missing. In the present study, we aimed to investigate CMD in patients hospitalized with COVID‐19, and to understand whether there is a relationship between biomarkers of myocardial injury, myocardial strain and inflammation and CMD.Methods39 patients that were hospitalized with COVID‐19 and 40 control subjects were included to the present study. Biomarkers for myocardial injury, myocardial strain, inflammation, and fibrin turnover were obtained at admission. A comprehensive echocardiographic examination, including measurement of coronary flow velocity reserve (CFVR), was done after the patient was stabilized.ResultsPatients with COVID‐19 infection had a significantly lower hyperemic coronary flow velocity, resulting in a significantly lower CFVR (2.0 ± 0.3 vs. 2.4 ± 0.5, p < .001). Patients with severe COVID‐19 had a lower CFVR compared to those with moderate COVID‐19 (1.8 ± 0.2 vs. 2.2 ± 0.2, p < .001) driven by a trend toward higher basal flow velocity. CFVR correlated with troponin (p = .003, r: −.470), B‐type natriuretic peptide (p < .001, r: −.580), C‐reactive protein (p < .001, r: −.369), interleukin‐6 (p < .001, r: −.597), and d‐dimer (p < .001, r: −.561), with the three latter biomarkers having the highest areas‐under‐curve for predicting CMD.ConclusionsCoronary microvascular dysfunction is common in patients with COVID‐19 and is related to the severity of the infection. CMD may also explain the “cryptic” myocardial injury seen in patients with severe COVID‐19 infection.

Sublingual Boosting with a Novel Mucoadhesive Thermogelling Hydrogel Following Parenteral CAF01 Priming as a Strategy Against Chlamydia trachomatis.

Chlamydia trachomatisis the most prevalent sexually transmitted disease of bacterial origin. The high number of asymptomatic cases makes it difficult to stop the transmission, requiring vaccine development. Herein, a strategy is proposed to obtain local genital tract immunity againstC. trachomatisthrough parenteral prime and sublingual boost. Subcutaneous administration of chlamydia CTH522 subunit vaccine loaded in the adjuvant CAF01 is combined with sublingual administration of CTH522 loaded in a novel thermosensitive and mucoadhesive hydrogel. Briefly, a ternary optimized hydrogel (OGEL) with desirable biological and physicochemical properties is obtained using artificial intelligence techniques. This formulation exhibits a high gel strength and a strong mucoadhesive, adhesive and cohesive nature. The thermosensitive properties of the hydrogel facilitate application under the tongue. Meanwhile the fast gelation at body temperature together with rapid antigen release should avoid CTH522 leakage by swallowing and increase the contact with sublingual tissue, thus promoting absorption.In vivostudies demonstrate that parenteral-sublingual prime-boost immunization, using CAF01 and OGEL as CTH522 vaccine carriers, shows a tendency to increase cellular (Th1/Th17) immune responses when compared to mucosal or parenteral vaccination alone. Furthermore, parenteral prime withCAF01/CTH522followed by sublingual boosting with OGEL/CTH522 elicits a local IgA response in the genital tract.

Surgical management of sublingual salivary mucocele (ranula) in a Maltese dog- a case report

A 10-year-old Maltese male dog was brought to the Shahedul Alam Quadery Teaching Veterinary Hospital (SAQTVH), Chattogram Veterinary and Animal Sciences University (CVASU) with the complaint of gradually enlarged soft swelling ventral to the left side of the tongue during the last four days with a history of difficult swallowing, abnormal protrusion of the tongue and excessive salivation. On clinical examination, soft, fluctuant, painless mass was palpated physically in the left side of sublingual tissues just beneath the tongue. The respiratory rate, heart rate and rectal temperature were within the normal values. Radiographic examination revealed a radio-lucent mass on the right lateral view, an anechoic round structure was found on ultrasonographic examination. Paracentesis of the mass reveals clear saliva-like fluid, which was mucoid. Based on the history, clinical examination and imaging findings, the condition was diagnosed as sublingual salivary mucocele (Ranula), which was corrected surgically under inhalation anesthesia. Antibiotic, antihistaminic and pain killer was administered postoperatively. The dog starts fed normally after three days of surgery and completely recovered after 5 days. Surgical excision can be an effective treatment for sublingual salivary mucocele in dogs.

Characterization of Immune Cells in Oral Tissues of Non-human Primates.

The oral mucosa contains distinct tissue sites with immune niches capable of either immunogenic or tolerogenic responses. However, immune cell compositions within oral mucosal tissues at homeostasis have not been well-characterized in human relevant tissues. Non-human primates (NHP) are a major model for the human immune system and oral anatomy, and therefore improved understanding of NHP oral immune cell populations can provide important insights for studying disease pathologies and developing therapies. Herein, we characterize immune cell types of three sites within the oral cavity (buccal, sublingual, lingual tonsil) sampled by biopsy and cytobrush in pigtail macaques. Tonsil biopsies had more T-cells, dendritic cells (DCs), DC subtypes, and CD4+ T-cells than buccal or sublingual biopsies when normalized by tissue mass. Biopsy proved to collect more immune cells than cytobrushes, however frequencies of CD45+ subpopulations were comparable between methods. Live cells isolated from biopsied tonsils had greater CD45+ leukocyte frequencies (mean 31.6 ± SD 20.4%) than buccal (13.8 ± 4.6%) or sublingual (10.0 ± 5.1%) tissues. T-cells composed more than half of the CD45+ population in sublingual tissue (60.1 ± 9.6%) and the tonsil (54.6 ± 7.5%), but only 31.9 ± 7.2% in buccal samples. CD20+ B-cells composed a greater percentage of CD45+ leukocytes in the tonsil (12.8 ± 9.1%) than buccal (1.2 ± 1.0%) or sublingual tissues (0.8 ± 1.2%). Immune population comparisons are also made between sex and age. These results present an important step for understanding the oral immune environment, oral disease, and site-specific therapy development.

New Noninvasive Methods to Evaluate Microvascular Structure and Function.

The structural and functional alterations of microvessels are detected because of physiological aging and in several cardiometabolic diseases, including hypertension, diabetes, and obesity. The small resistance arteries of these patients show an increase in the media or total wall thickness to internal lumen diameter ratio (MLR or WLR), often accompanied by endothelial dysfunction. For decades, micromyography has been considered as a gold standard method for evaluating microvascular structural alterations through the measurement of MLR or WLR of subcutaneous small vessels dissected from tissue biopsies. Micromyography is the most common and reliable method for assessing microcirculatory endothelial function ex vivo, while strain-gauge venous plethysmography is considered the reference technique for in vivo studies. Recently, several noninvasive methods have been proposed to extend the microvasculature evaluation to a broader range of patients and clinical settings. Scanning laser Doppler flowmetry and adaptive optics are increasingly used to estimate the WLR of retinal arterioles. Microvascular endothelial function may be evaluated in the retina by flicker light stimulus, in the finger by tonometric approaches, or in the cutaneous or sublingual tissues by laser Doppler flowmetry or intravital microscopy. The main limitation of these techniques is the lack of robust evidence on their prognostic value, which currently reduces their widespread use in daily clinical practice. Ongoing and future studies will overcome this issue, hopefully moving the noninvasive assessment of the microvascular function and structure from bench to bedside.

Mucoadhesive Electrospun Nanofiber-Based Hybrid System with Controlled and Unidirectional Release of Desmopressin.

The sublingual mucosa is an attractive route for drug delivery, although challenged by a continuous flow of saliva that leads to a loss of drug by swallowing. It is of great benefit that drugs absorbed across the sublingual mucosa avoid exposure to the harsh environment of the gastro-intestinal lumen; this is especially beneficial for drugs of low physicochemical stability such as therapeutic peptides. In this study, a two-layered hybrid drug delivery system was developed for the sublingual delivery of the therapeutic peptide desmopressin. It consisted of peptide-loaded mucoadhesive electrospun chitosan/polyethylene oxide-based nanofibers (mean diameter of 183 ± 20 nm) and a saliva-repelling backing film to promote unidirectional release towards the mucosa. Desmopressin was released from the nanofiber-based hybrid system (approximately 80% of the loaded peptide was released within 45 min) in a unidirectional manner in vitro. Importantly, the nanofiber–film hybrid system protected the peptide from wash-out, as demonstrated in an ex vivo flow retention model with porcine sublingual mucosal tissue. Approximately 90% of the loaded desmopressin was retained at the surface of the ex vivo porcine sublingual mucosa after 15 min of exposure to flow rates representing salivary flow.

Sialocele of Submandibular Gland, an Unreported Complication of Bilateral Sagittal Split Osteotomy

Bilateral sagittal split osteotomy is a routine procedure with predictable and well-known complications. The authors report a thitherto unreported complication of bilateral sagittal split osteotomy presenting as a postoperative sialocele of submandibular salivary gland tissue in the floor of the mouth. The sialocele was probably caused by overinstrumentation and injury to sublingual salivary tissues or Wharton's duct during bicortical drilling or screw fixation. This iatrogenic sialocele was managed conservatively with multiple aspiration and compression dressings. Although rare and unreported so far this complication may be included in the preoperative consent process.

Assessment of epinephrine sublingual stability and permeability pathways to enhance its permeability for the treatment of anaphylaxis

Prompt epinephrine (Epi) injection using auto-injectors is the initial life-saving out-of-hospital treatment for anaphylaxis. However, patients and healthcare providers are eagerly awaiting a more convenient alternative dosage form that would overcome auto-injectors drawbacks.Previously, we extensively evaluated multiple alternative fast-disintegrating sublingual Epi tablet (FDSTs) formulations. However, the sublingual stability of Epi and effect of modifying the sublingual microenvironment pH on its stability and transport pathways were not yet fully investigated.Results depicted that Epi remained sufficiently stable at various pHs in human saliva and porcine sublingual tissue's extract. Epi permeability (EP) through excised porcine sublingual membrane was greatest at pH 8.0 (p < 0.05), 11-fold higher than the negative control (Epi at pH 6.8). Sodium carbonate (Na Carb) 0.75% was the most efficient buffer to modify Epi solution pH to 8.0. Both sodium dodecyl sulfate (SDS) 0.075% and palmitoyl-DL-carnitine chloride (PCC) 1.2% increased paracellular EP 10-fold and 3-fold, respectively; however, both demonstrated a delayed enhancement (>5 min). Meanwhile, Na Carb and SDS combination increased EP 23-fold without a delay.It is evident that pH-modifiers or their SDS combination showed promising potential to enhance Epi sublingual permeability and further reduce the required Epi dose using FDSTs as a feasible alternative to Epi auto-injectors.

Formulation, characterization, optimization, and in-vivo performance of febuxostat self-nano-emulsifying system loaded sublingual films

Febuxostat (FXS) is a potent antigout drug with poor water solubility and relative high first-pass effect leading to moderate oral bioavailability (<49%). This study aimed to increase FXS solubility and bioavailability by optimizing sublingual fast-dissolving films (SFs) containing a selected FXS self-nano-emulsifying system (s-SNES) previously prepared by our team. The s-SNES was loaded into SFs by solvent casting technique. A full factorial design (32) was applied to study the effects of polymer and plasticizer types on mechanical characteristics and the dissolution profile of FXS from the SFs. Numerical optimization was performed to select the SF having highest desirability according to predetermined characteristics. The optimized SF (O-SF) contained 1 g of s-SNES, polyvinylpyrrolidone K30 (6%w/v), polyethylene glycol 300 (20%w/w of polymer wt.), and Avicel PH101 (0.5%w/v). O-SF showed good permeation of FXS through sheep sublingual tissue. Storage of O-SF for three months showed no significant change in the FXS dissolution profile. In-vivo performance of O-SF in rabbits was compared to that of oral marketed tablets (Staturic® 80 mg). A cross-over design was applied and pharmacokinetic parameters were calculated after ensuring absence of sequence effect. Statistical analysis revealed better performance for O-SF with significantly higher C max, AUC0–24, AUC0–∞, apparent t 1/2 together with lower t max, and apparent kel than marketed tablets. Relative bioavailability of O-SF compared to the marketed tablet was found to be 240.6%. This confirms the achievement of the study aims of improving dissolution rate and bioavailability of FXS using a patient-wise convenient formula.

Mucoadhesive wafers composed of binary polymer blends for sublingual delivery and preservation of protein vaccines

The objective of this study is to develop a simple biopolymer platform of mucoadhesive wafers that enables effective sublingual delivery and preservation of protein vaccines. The wafers were composed of a series of binary polymer blends of carboxymethylcellulose (CMC) and alginate (ALG). Varying the ratio between CMC and ALG resulted in wafers with different microstructure, mechanical properties, disintegration time, and release kinetics of model compounds. Wafers with high CMC content were highly mucoadhesive to sublingual mucosal tissue and could withstand extensive washing, leading to improved protein permeation into the tissue. On the other hand, wafers with high ALG content were not only mechanically robust, but also able to protect a model enzyme (β-galactosidase) against lyophilization and heat challenge. HIV gp140 protein loaded in wafers of the optimal composition could be stored and transported without cold chain, while maintaining antigen-specific immunogenicity after sublingual vaccination in mice. These findings established that the CMC/ALG binary blend polymer wafers have the potential to improve the sublingual delivery and storage stability of protein-based vaccines.

Macrocirculation and Microcirculation: The "Batman and Superman" Story of Critical Care Resuscitation.

Macrocirculation and Microcirculation: The "Batman and Superman" Story of Critical Care Resuscitation.