Gamma Scintigraphy Research Articles

Imaging Aerosol Deposition with Two-Dimensional Gamma Scintigraphy.

Several imaging modalities have been employed to quantify lung dose and the distribution of the dose of orally inhaled aerosols in vivo. Two-dimensional (2D, or planar) imaging using gamma scintigraphy is the most widely used of these modalities. Two-dimensional gamma scintigraphy studies are accomplished using a single- or dual-headed gamma camera. The formulation to be tested is admixed with the gamma emitting radioisotope 99mtechnetium, which serves as a surrogate for the drug. This article provides details as to how 2D gamma scintigraphy images should be acquired and analyzed using recently standardized methods. Based on the new guidelines, the investigator should confirm that the drug formulation is unchanged with the addition of the radioisotope, determine the amount of radioactivity needed for inhalation to obtain appropriate radioactivity counts in the lungs, perform quality control procedures for the gamma camera, identify the lung borders of the study subject using a reference image such as an X-ray computed tomography scan, a ventilation scan, or a transmission scan, acquire a lung transmission image to correct for attenuation of radioactivity by lung tissue, instruct the subject how to inhale the radiolabel-drug mixture and record associated breathing parameters, acquire anterior and/or posterior views of the lungs and any other regions of interest (i.e., oropharynx, stomach) and assess the acquired images for total and regional dose to the lungs. Total dose should be assessed after identification of the right lung border and appropriate correction for tissue attenuation. Regional dose should be quantified as a normalized outer/inner deposition ratio (O/I) and expressed as the penetration index (PI). Mass balance should be performed as needed. By following the standardized methods, 2D gamma scintigraphy data from studies in different laboratories may be compared and combined, leading to multi-center studies and more rapid development of new medications and devices for inhaled therapies.

S1058 A Scintigraphic Study to Evaluate the Safety, Tolerability, and Functions of a Drug Delivery System (DDS) Device in Healthy Subjects in Fasted State

Introduction: The clinical remission in moderate to severe ulcerative colitis (UC) and Crohn’s disease has plateaued at ∼15-20% even with the approval of multiple biologics/drugs. The ATLAS study demonstrated that the lack of adequate amount of drug at the diseased site is responsible for limited clinical benefit. The Drug Delivery System (DDS) is an ingestible electronic targeted delivery device containing a localization system to identify colon entry (S4 calls) based on the gastrointestinal (GI) anatomy and deliver a bolus dose of a therapeutic compound to the colon mucosa to improve efficacy and reduce systemic toxicity. This was an open-label and single-center study to evaluate the safety and tolerability, and functions of a DDS device using gamma scintigraphy in normal healthy volunteers (NHV) in the fasted state. Methods: Each subject was fasted overnight for a minimum of 8 hrs. and dosed with a single DDS device before resuming a normal diet at 4 hrs. post-dosing. Each capsule was filled with radioactive marker 111In-DTPA to identify DDS localization and to visualize payload release; water radiolabeled with 99mTc-DTPA was co-administered with the DDS to delineate GI landmarks by gamma scintigraphy. The GI transit of DDS and delivery location were confirmed by serial scintigraphy imaging and compared with the localization data in the recovered capsule. Results: Twelve male subjects were enrolled and treated in the study. There were no reported device-related adverse events in any subject who completed the study. GI transit metrics of DDS were consistent with GI residence times observed amongst NHV. There was no early release of the radio payload prior to S4 calls being made by all 12 devices. Ten of twelve devices (83%) showed correct localization calls in the colon, confirmed by scintigraphy image analysis. In addition, among devices that showed release of the 111In-DTPA payload, the dispersion of the radioactive marker completely covered the colon over time and spread to match the 99mTc-DTPA water coverage area from the site of DDS release throughout the remainder of the colon (Figure). Conclusion: This study demonstrated that DDS was well-tolerated and had a favorable safety profile, and the device functioned as intended in identifying and releasing drug payload in the colon. DDS provides more precise dosing with a liquid formulation at a pre-determined location in the GIT and delivers therapeutics to the site of disease to improve efficacy.Figure 1.: Cumulative distribution of radiotracer 111In-DTPA release from Drug Delivery System (DDS) post-dose A. the first release of 111In-DTPA was observed post-dose in the cecum/ascending colon. B. Distribution of released 111In-DTPA over time in the colon.

S1061 A Scintigraphic Study to Evaluate the Localization and Delivery Function of a Drug Delivery System (DDS) Device in Patients With Active Ulcerative Colitis (UC) in a Fasted State

Introduction: The clinical remission in moderate to severe ulcerative colitis (UC) and Crohn’s has plateaued at ∼15-20% even with the approval of multiple biologics/drugs. Altas study clearly demonstrated that the lack of adequate amount of drug at the diseased site is responsible for limited clinical benefit. The Drug Delivery System (DDS) is an ingestible electronic targeted delivery device containing a localization system to identify colon entry based on the gastrointestinal (GI) anatomy and deliver a bolus dose of a therapeutic compound to the colon mucosa to improve efficacy and reduce systemic toxicity. DDS was shown to be well-tolerated and functioned as intended in identifying and releasing radiotracer in the colon of normal healthy volunteers (NHV). Here, we aim to evaluate the safety and functionality of DDS in active UC patients in a fasted state. Methods: Patients with endoscopy and histology confirmed UC and active UC status defined as having Mayo score ≥ 2 or elevated Fecal Calprotectin Protein or high sensitivity C-reactive protein within one month of the screening visit were eligible for the study. Each patient was fasted overnight and dosed with a single DDS capsule prior to resuming a normal diet. Each capsule was filled with radioactive marker 111In-DTPA to independently identify DDS localization and to visualize payload release; water radiolabeled with 99mTc-DTPA was co-administered with the DDS to delineate GI landmarks by gamma scintigraphy. The GI transit of DDS and delivery location of the radiotracer were confirmed by serial gamma scintigraphy imaging. Results: This is a preliminary analysis of an ongoing study of active UC patients with Mayo scores between 3-8 enrolled and dosed in the study. GI transit metrics of DDS were consistent with the variable GI motility and the frequent bowel movements observed among active UC patients. DDS device demonstrated correct localization identification of colon entry and release of radiotracer in the colon regardless of variable GI motility, the level of inflammation, or blood in the colon of UC patients compared to NHV (Table), confirmed by gamma scintigraphy image analysis. The dispersion of the radiotracer adequately covered the colon from the site of release throughout the remainder of the colon. Conclusion: This result demonstrated that DDS functioned as intended in identifying and releasing the payload in the colon regardless of GI motility or disease status. Table 1. - GI transits, Residence Time, and Radiotracer (111In-DTPA) Delivery Location of DDS Device post-dose in Active UC patients (PM-602) and Normal Healthy Volunteers (NHV) (PM-601) Subject Mayo score Gastric emptying time (min) Small intestine Residence time (min) Arrival Time at Cecum (min) 1st Capsule release In-111 (min) Capsule location at the time of 1st capsule release Capsule Recovery Time (hrs) No. of Bowel Movements required to recover Capsule 602-116-001 6 104 169 273 324 Cecum 47.67 3 602-116-002 3 23 122 145 190 Cecum 26.50 3 602-116-003 8 38 292 330 354 Cecum 32.83 5 601-NHV (N = 11)* Median N/A 29 228 270 368 Cecum/Asc Colon/Splenic Flexure 23.99 1 (n=6)2 (n=4)3 (n=1) *Excluded one subject due to anomalous transit of the DDS device from the stomach to the duodenum and then back into the stomach.

In Vitro Regional Deposition of Nasal Sprays in an Idealized Nasal Inlet: Comparison with In Vivo Gamma Scintigraphy.

To compare in vitro regional nasal deposition measurements using an idealized nasal airway geometry, the Alberta Idealized Nasal Inlet (AINI), with in vivo regional deposition for nasal drug products. One aqueous solution formulation (NasalCrom), one aqueous suspension formulation (Nasonex) and one nasal pressurized metered dose spray device (QNASL) were selected. Two spray orientation angles, 60° and 45° from the horizontal, were selected. A steady inhalation flow rate of 7.5 L/min was selected to simulate slow inhalation through a single nostril. After actuation, the AINI was disassembled. The mass of drug deposited in each region and a downstream filter, representing penetration of drug to the lungs, was determined using ultraviolet-visible (UV-Vis) spectrophotometry. No filter (lung) deposition was detected for NasalCrom or Nasonex. Filter deposition ranged from 6 to 11% for QNASL. For NasalCrom, 45% to 69% of the dose deposited in the AINI was deposited in the vestibule and 31% to 55% was deposited in the turbinates; for Nasonex, 66% to 74% (vestibule) and 26% to 34% (turbinates); for QNASL, 90% to 100% (vestibule) and 0% to 10% (turbinates). No statistically significant difference was observed between regional deposition in vivo and in vitro for any of the formulations, except that nasopharyngeal deposition with Nasonex differed by less than 1.56% from in vivo, which while statistically significant, is unlikely to be clinically significant. The AINI was able to mimic regional in vivo deposition for nasal drug products, permitting differentiation between devices based on regional deposition.

Gastric Emptying of Maltodextrin versus Phytoglycogen Carbohydrate Solutions in Healthy Volunteers: A Quasi-Experimental Study.

Preoperative carbohydrate beverages have been shown to be beneficial in improving patient outcomes. There have been several investigations into the safety of maltodextrin as a preoperative carbohydrate. Although alternative preoperative carbohydrate sources have been proposed, there have been few investigations into the safety and gastric emptying of novel carbohydrate beverages. The present study aimed to compare the gastric emptying of phytoglycogen and maltodextrin to evaluate safety for use as presurgical carbohydrate beverages. In a quasi-experimental design, ten healthy participants orally consumed either a 12.5% maltodextrin or a 12.5% phytoglycogen solution. Gamma scintigraphy was used to evaluate gastric emptying at baseline at 45, 90, and 120 min. Serum insulin and serum glucose were measured at baseline at 15, 30, 45, 60, 90, and 120 min. Gastric volume was significantly lower in the phytoglycogen group at 45 min (p = 0.01) and 90 min (p = 0.01), but this difference lost significance at 120 min (p = 0.17). There were no significant differences between treatments for serum insulin or serum glucose at any time point. This study indicates that the gastric emptying of phytoglycogen is comparable to maltodextrin at 120 min after ingestion, opening the opportunity for the study of alternative carbohydrates for utilization as preoperative carbohydrates.

Respiratory Tract Deposition of E-Cigarette Particles.

Total and regional deposition of inhaled electronic cigarette (E-cig) particles in the respiratory tract (RT) depends on both physical properties of the inhaled particles and biological factors of users, for example, breathing pattern or puff profile, airway anatomy, and regional ventilation. Accurate particle sizing of E-cig aerosols is essential for predicting particle deposition in the RT. Studies using a variety of sizing methods have shown mass median aerodynamic diameters ranging from 0.2 to 1.2 um and secondary count diameters in the ultrafine range (<0.1 μm). Incorporating these particle sizes into a multiple-path particle dosimetry (MPPD) model shows 10% to 45% total lung deposition by mass and 30% to 80% for ultrafine particles depending on the breathing patterns. These predictions are consistent with experimental measures of deposition fraction of submicron and ultrafine particles. While box-mod-type E-cig devices allow for full "direct-lung" inhalations of aerosol, the more recent pod-based, and disposable E-cigs (e.g., JUUL, Puff Bar, Stig) deliver the aerosol as a "mouth-to-lung" puff, or bolus, that is inhaled early in the breath followed to various degrees by further inhalation of ambient air. Measurement of realistic ventilation patterns associated with these various devices may further improve deposition predictions. Finally, while in vivo measures of RT deposition present a challenge, a recent methodology to radiolabel E-cig particles may allow for such measurements by gamma scintigraphy. Supported by NIH/NHLBI R01HL139369. © 2022 American Physiological Society. Compr Physiol 12: 1-10, year.

Investigating the lesion detectability of Tc-99m planar scintigraphy acquired with LEHRS collimator for patients with different body sizes: A phantom study.

PurposeThe aim of this work was to investigate the lesion detectability of Tc‐99m planar scintigraphy acquired with a low‐energy high‐resolution and sensitivity (LEHRS) collimator and processed by Clarity 2D for patients with different body sizes through phantom study.MethodsA NEMA IEC body phantom set was covered by two layers of 25‐mm‐thick bolus to construct phantom in three different sizes. All image data were performed on a Discovery NM/CT 870 DR with an LEHRS collimator and processed by Clarity 2D with blend ratio a of 0%, 20%, 40%, 60%, 80%, and 100%. The lesion detectability in gamma scintigraphy was evaluated by calculating the contrast‐to‐noise ratio (CNR). Multiple linear regression methods were used to analyze the impact of body size, target size, and Clarity 2D blending weight on the lesion detectability of Tc‐99m planar scintigraphy.ResultsIt was found that changing the blend ratio could improve CNR, and this phenomenon was more significant in anterior view than in posterior view. Our results also suggested that the blend ratio should be selected according to patient body size in order to maintain consistent CNR. Hence, when a blend ratio of 60% was used for a patient before cancer treatment, a lower blend ratio should be used for the same patient experiencing treatment‐related weight loss to achieve consistent lesion detectability in Tc‐99m planar scintigraphy acquired with LEHRS and processed by Clarity 2D.ConclusionThe magnitude of photon attenuation and scattering is higher in patients with larger body size, so Tc‐99m planar scintigraphy usually has lower lesion detectability in obese patients. Although photon attenuation and scattering are inevitable during image formation, their impacts on image quality can be eased by employing appropriate image protocol parameters.

Targeted colonic release formulations of mesalazine – A clinical pharmaco-scintigraphic proof-of-concept study in healthy subjects and patients with mildly active ulcerative colitis

Colonic targeting of orally applied therapeutic drugs remains a challenge. Tablet coatings relying on gastrointestinal pH and colonic bacterial enzymes as triggers in association with an inner alkaline layer are expected to improve targeting efficiency. Mesalazine release from three differently coated tablets labelled with 1 MBq 153Sm was characterised in a single centre, open-label, parallel group study in nineteen healthy subjects and seven patients with mildly active ulcerative colitis. Two semi-organic and one aqueous-based outer coating with different ratios of enteric polymer and resistant starch were tested. All coatings showed comparable release lagtimes in biorelevant dissolution media and were not affected by neutron-activation of the samarium tracer. Mesalazine pharmacokinetics and gamma scintigraphy were used to characterise drug release, anatomical site of tablet disintegration and gastrointestinal transit. Initial tablet disintegration occurred at the ileo-caecal junction or beyond in 92 % of the subjects. Time to initial tablet disintegration was inversely correlated with maximal plasma concentrations and systemic mesalazine exposure. Although high inter-subject variability precluded detection of differences between solvent types and different enteric polymer to polysaccharide ratios, the dual pH and enzymatic triggered release system in combination with an inner alkaline layer promoted mesalazine release at the target site with high accuracy.

Spread of Mesalazine Rectal Foam after Single Dose in Mild Ulcer Patients

Background: The rectal foam enemas were used for ulcerative colitis of distal regions due to its desired efficacy and less side effects. The spread and persistence of the drug plays a key role in the treatment. Therefore, the objective of the present study is to study the spread and persistence of Salofalk (Mesalazine foam Enema), manufactured by Dr. Falk Pharma GmbH (mesalazine) rectal foam in mild ulcerative colitis patients.&#x0D; Methods: This is an open label, uncontrolled prospective study in ulcerative colitis patients. The patients received 2 g of mesalazine rectal foam (labelled with Tcm99) in two actuations (30 mL). The spread of the radiolabeled formulation was assessed over a period of 4 h by gamma scintigraphy.&#x0D; Results: The formulation was retained by the patients till 4 h imaging period. The foam spread in rectum, sigmoid colon and descending colon. The percentage radioactive dose exposed is more in sigmoid colon compared to rectum and descending colon in 4 h imaging period. The spread of the foam extended till descending colon for two out of 4 patients.&#x0D; Conclusion: The study results are consistent with the previous studies, and it supports the label indication. The obtained data of the present study provides in vivo evidence of the spread of formulation in the desired site of action.

Hypolipidemic effect of [6]-Gingerol-loaded Eudragit polymeric nanoparticles in high-fat diet-induced rats and Gamma scintigraphy evaluation of gastric-retention time

Nanocarriers for Alzheimer’s disease: Research and patent updateKamla Pathak, Shashi Kiran Mishra, Amit Porwal, Shiv Bahadur

Effect of airway clearance therapies on mucociliary clearance in adults with cystic fibrosis: A randomized controlled trial.

Cystic fibrosis (CF) is an inherited disorder causing impaired mucociliary clearance within the respiratory tract, and is associated with bronchiectasis, chronic respiratory infections, and early death. Airway clearance therapies have long been a cornerstone of management of individuals with CF, although evidence supporting their use is lacking. We designed a randomized controlled trial to quantitatively compare the effects of different forms of airway clearance on mucociliary clearance. Three different physiotherapy methods to augment cough-clearance were studied in addition to cough-clearance alone: high-frequency chest-wall oscillating vest, oscillatory positive expiratory pressure, and whole-body vibration. We used gamma scintigraphy after inhalation of radiolabeled particles to quantify mucus clearance before, during, and after physiotherapy. As secondary endpoints, we measured concentrations of small molecules in exhaled breath that may impact mucus clearance. Ten subjects were enrolled and completed study procedures. No differences were identified between any method of airway clearance, including cough clearance alone. We did identify changes in certain small molecule concentrations in exhaled breath following airway clearance. Due to the limitations of this study, we do not believe the negative results suggest a change in clinical practice with regard to airway clearance. Findings pertaining to small molecules in exhaled breath may serve as future opportunities for study.

A single-dose, open-label, randomized, scintigraphic study to investigate the gastrointestinal behavior of 2 triple-combination cold products (acetaminophen, phenylephrine, and dextromethorphan) in healthy male volunteers

BackgroundCommon cold symptoms may be mitigated by products in caplet, nasal spray, and oral solution formulations, although variations exist in the bioavailability of the active ingredients contained within these products. Rapid gastric emptying (GE) of these active ingredients is important for reducing the delay between drug absorption and onset of cold symptom relief. Hot drink cold remedies are associated with greater comfort and may enhance the bioavailability of active ingredients. The objective of this study was to characterize the gastrointestinal transit of powder (reconstituted in hot water) and caplet formulations of commercially available multisymptom cold medications.MethodsThis was an open-label, single-dose, parallel-group study. Healthy male adults under fasted conditions were randomized 1:1 to receive a single dose of radiolabeled Theraflu Daytime Severe Cold and Cough powder for oral solution or radiolabeled Theraflu ExpressMax Daytime Severe Cold and Cough caplet. External gamma scintigraphy was utilized to monitor GE and intestinal transit of two radiolabeled drug formulations.ResultsA total of 28 participants completed the study. The mean ± SE GE onset times were 1.1 ± 0.3 min and 8.5 ± 1.8 min for powder and caplet formulations, respectively. The mean ± SE GE completion times were 121 ± 13 min and 65 ± 13 min, respectively. Despite the similar mean times to GE25%, the powder had later mean GE50% (23 ± 3.0 vs 16 ± 3.2 min, respectively) and GE90% (85 ± 12 vs 36 ± 9 min, respectively) than caplets. Caplets had a shorter overall GE half-life, lower total gastric exposure, and faster transit time through the small intestine versus the powder formulation. No serious safety events were observed.ConclusionThe results of this study in healthy male adults suggest that the Theraflu powder formulation had a more rapid GE onset but longer time to GE completion than the caplet formulation.Trial registrationClinicalTrials.govNCT03415243

Lung Deposition of Inhaled Extrafine Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrronium Bromide in Healthy Volunteers and Asthma: The STORM Study.

Background:An extrafine formulation triple therapy combination of beclomethasone dipropionate (BDP), formoterol fumarate (FF), and glycopyrronium bromide (GB) has been developed for the maintenance treatment of asthma and chronic obstructive pulmonary disease. This study used gamma scintigraphy to evaluate the intrapulmonary and extrapulmonary in vivo deposition of BDP/FF/GB, and the intrapulmonary regional distribution of the deposited formulation.Methods:This open-label uncontrolled nonrandomized single-dose study recruited 10 healthy volunteers and 9 patients with asthma. After a krypton-81m (81mKr) ventilation scan was conducted, subjects inhaled study drug (four inhalations of BDP/FF/GB 100/6/12.5 μg radiolabeled using technetium-99 m [99mTc]) through pressurized metered-dose inhaler, and a series of scintigraphic images were taken. The primary objective was to evaluate intrapulmonary drug deposition of BDP/FF/GB, determined as the percentage of nominal (i.e., metered) dose. Secondary endpoints included central/peripheral deposition ratio (C/P), and the standardized central/peripheral ratio (sC/P; 99mTc aerosol C/P/81mKr gas C/P).Results:All participants completed the study, with all scintigraphy procedures performed at one site. In patients with asthma, mean ± standard deviation intrapulmonary deposition was 25.50% ± 6.81%, not significantly different to that in healthy volunteers (22.74% ± 9.19%; p = 0.4715). Approximately half of the lung dose was deposited in the peripheral region of the lung (fraction deposited 0.52 ± 0.07 and 0.49 ± 0.06 in healthy volunteers and patients with asthma, respectively), resulting in C/P ratios of 0.94 ± 0.25 and 1.06 ± 0.25, respectively, with sC/P ratios of 1.80 ± 0.40 and 1.94 ± 0.38. Deposition patterns were similar in the two populations. BDP/FF/GB was well tolerated.Conclusions:This study confirmed that the extrafine particles delivered by BDP/FF/GB penetrate the peripheral areas of the lungs, with a similar proportion of particles deposited in the central and peripheral regions. Importantly, the deposition patterns were similar in healthy volunteers and patients with asthma, suggesting that disease characteristics are unlikely to impact drug deposition.Clinical Trial Registration number: NCT03795350.

Biodistribution Study of Niosomes in Tumor-Implanted BALB/C Mice Using Scintigraphic Imaging.

The purpose of this work was to study the biodistribution of niosomes in tumor-implanted BALB/c mice using gamma scintigraphy. Niosomes were first formulated and characterized, then radiolabeled with Technetium-99 m (99mTc). The biodistribution of 99mTc-labeled niosomes was evaluated in tumor-bearing mice through intravenous injection and imaged with gamma scintigraphy. The labeled complexes possessed high radiolabeling efficiency (98.08%) and were stable in vitro (>80% after 8 h). Scintigraphic imaging showed negligible accumulation in the stomach and thyroid, indicating minimal leaching of the radiolabel in vivo. Radioactivity was found mainly in the liver, spleen and kidneys. Tumor-to-muscle ratio indicated a higher specificity of the formulation for the tumor area. Overall, the formulated niosomes are stable both in vitro and in vivo, and show preferential tumor accumulation.

Radioprotective effects of melatonin against varying dose rates on radiotherapy-induced salivary gland damage scintigraphy findings

The aim of present study was to evaluate the acute radioprotective effect of melatonin against radiotherapy-induced rat salivary gland damage by applying salivary gland scintigraphy imaging technique in varying dose rates.Forty-eight Sprague Dawley rats were randomly distributed into six group: the control group, only melatonin (MEL) group, flattening filter (FF-RT) and flattening filter free (FFF-RT) only radiotherapy groups and radiotherapy plus melatonin groups, (FF-RT)+Mel and (FFF-RT)+Mel. The head and neck region of experimental rat was irradiated with in a single fraction of a 16 Gy in FF and FFF modes. Melatonin was administered at a single dose of 10 mg/kg through intraperitoneal injection, 15 min before radiation exposure. The assessment of salivary gland function was performed using gamma scintigraphy prodecure before and after radiotherapy.Statistically significant difference in target-to-background (T/B) ratio, between the only melatonin and control groups were not observed (p = 0.981). However, when acute effects of irradiation are considered after radiotherapy, salivary gland T/B ratios was a significant difference (p < 0.001). In the only radiotherapy groups applied considering in the FF and FFF options no statistically significant difference was observed in the salivary gland T/B ratio FF-RT group compared to the FFF-RT group (p = 0.999). The T/B ratio between the radiotherapy plus melatonin groups for FF-RT and FFF-RT beam was significantly higher in the compared to the only radiotherapy (p < 0.05).In conclusion, our findings suggest that melatonin is a radioprotective agent for treatment of low and high dose rate against acute salivary gland damage during radiotherapy of head and neck cancer.

Fabrication, characterization and evaluation of the efficacy of gelatin/hyaluronic acid microporous scaffolds suffused with aloe-vera in a rat burn model.

Burn induced injuries are commonly encountered in civilian and military settings, leading to severe morbidity and mortality. Objective of this study was to construct microporous bioactive scaffolds of gelatin-hyaluronic acid suffused with aloe-vera gel (Gela/HA/AvG), and to evaluate their efficacy in healing partial-thickness burn wounds. Scaffolds were characterized using Fourier transform-infrared spectroscopy, Scanning electron microscopy, and Thermo-gravimetric analysis to understand intermolecular interactions and morphological characteristics. In-vitro fluid uptake ability and hemolytic index of test scaffolds were also determined. In-vitro collagenase digestion was done to assess biodegradability of scaffolds. Wound retraction studies were carried out in Sprague Dawley rats inflicted with partial-thickness burn wounds to assess and compare efficacy of optimized scaffolds with respect to negative and positive control groups. In-vivo gamma scintigraphy using Technetium-99m labeled Immunoglobulin-G (99mTc-IgG) as imaging agent was also performed to validate efficacy results. Histological and immunohistochemical comparison between groups was also made. Scaffolds exhibited mircoporous structure, with pore size getting reduced from 41.3 ± 4.3µm to 30.49 ± 5.7µm when gelatin conc. was varied from 1% to 5%. Optimized test scaffolds showed sustained in-vitro swelling behavior, were biodegradable and showed hemolytic index in range of 2.4-4.3%. Wound retraction study along with in-vivo gamma scintigraphy indicated that Gela/HA/AvG scaffolds were not only able to reduce local inflammation faster but also accelerated dermis regeneration. Immunohistochemical analysis, in terms of expression levels of epidermal growth factor and fibroblast growth factor-2 also corroborated in-vivo efficacy findings. Gela/HA/AvG scaffolds, therefore, can potentially be developed into an effective dermal regeneration template for partial-thickness burn wounds.

Pharmacoscintigraphic evaluation and antidiabetic efficacy of gliclazide-loaded 99mTc-labelled mucoadhesive microspheres

BackgroundThe current study was carried out to evaluate the possible application of Musa balbisiana starch in formulation of mucoadhesive microsphere for oral delivery of gliclazide (GLZ). The study objective was to improve the oral bioavailability along with prolongation of its duration of action for a better glycaemic control. Ionic gelation technique was employed in formulating the dosage form. Optimization of the batches was carried out by response surface methodology using 32 full factorial designs. The microsphere prepared was characterized for several parameters along with its in vitro release study. The gastrointestinal transit of the optimized batch of prepared microspheres after oral administration was studied in rabbits by using the gamma scintigraphy technique utilizing 99mTc as the labelling agent in the presence of stannous chloride. Also, the optimized batch was studied for its pharmacokinetic parameters. Moreover, the antidiabetic efficacy of the prepared microsphere was evaluated in rats by using the streptozotocin (STZ)-induced diabetic model.ResultsThe factorial design experiment resulted in an optimum formulation coded as F8. The compatible nature of the drug and excipient was revealed from FTIR, DSC and IST studies. The scanning electron micrographs also showed the occurrence of spherical microspheres having a smooth surface. The in vitro release study provided an evidence of an initial burst effect that was followed by a prolong release phase. The pharmacokinetic parameters justified the ability of the prepared dosage form in sustaining the drug release with a 2.7-fold enhancement in drug bioavailability. The images obtained during the gamma scintigraphy study suggested the gastro-retentive nature of the dosage form with the gastro-retentive ability for more than 4 h. Also, the pharmacodynamics study carried out in diabetic rat model confirmed about the better efficacy of the dosage form in lowering the elevated blood glucose level.ConclusionThe overall study data provide valuable information about the potential of this banana starch in formulation of a mucoadhesive dosage form that can be used for enhancement of bioavailability of drug-like gliclazide which in turn can provide a beneficial effect in the management of diabetes.

Lung Deposition of Surfactant Delivered via a Dedicated Laryngeal Mask Airway in Piglets.

It is unknown if the lung deposition of surfactant administered via a catheter placed through a laryngeal mask airway (LMA) is equivalent to that obtained by bolus instillation through an endotracheal tube. We compare the lung deposition of surfactant delivered via two types of LMA with the standard technique of endotracheal instillation. 25 newborn piglets on continuous positive airway pressure support (CPAP) were randomized into three groups: 1—LMA-camera (integrated camera and catheter channel; catheter tip below vocal cords), 2—LMA-standard (no camera, no channel; catheter tip above the glottis), 3—InSurE (Intubation, Surfactant administration, Extubation; catheter tip below end of endotracheal tube). All animals received 100 mg·kg−1 of poractant alfa mixed with 99mTechnetium-nanocolloid. Surfactant deposition was measured by gamma scintigraphy as a percentage of the administered dose. The median (range) total lung surfactant deposition was 68% (10–85), 41% (5–88), and 88% (67–92) in LMA-camera, LMA-standard, and InSurE, respectively, which was higher (p < 0.05) in the latter. The deposition in the stomach and nasopharynx was higher with the LMA-standard. The surfactant deposition via an LMA was lower than that obtained with InSurE. Although not statistically significant, introducing the catheter below the vocal cords under visual control with an integrated camera improved surfactant LMA delivery by 65%.

Nose to brain delivery of Efavirenz nanosuspension for effective neuro AIDS therapy: in-vitro, in-vivo and pharmacokinetic assessment

Efavirenz is inhibitor of non-nucleoside reverse transcriptase enzyme; BCS class II drug. The objective of the present research was to prepare and evaluate nanosuspension of Efavirenz for the treatment of neuro-AIDS. Efavirenz is the substrate for drug resistant proteins at BBB prone to efflux and could not reach brain with effective levels. Current need of the therapy is to develop drug delivery systems targeting viral reservoirs at effective concentration in the brain. With this need we developed Efavirenz nanosuspension for nose to brain drug transport to bypass blood brain barrier. Nanosuspension prepared with high-pressure homogenization had a mean particle size of 223 nm, PDI of 0.2 and -21.2 mV zeta potential. Histopathology study on goat nasal mucosa showed no adverse effects of formulation on nasal tissues. Gamma scintigraphy study and in-vivo study on Wistar rat model reveals drug transport to the CNS after nasal administration. Pharmacokinetic parameters and drug targeting potential of 99.46 % suggest direct nose to brain transport of Efavirenz nanoparticle. Results reveal that nose to brain delivery of Efavirenz is the best possible alternative for neuro –AIDS treatment.

Effect of a Surfactant Additive on Drug Transport and Distribution Uniformity After Aerosol Delivery to Ex Vivo Lungs.

Background: Inhaled drug delivery can be limited by heterogeneous dose distribution. An additive that would disperse drug over the internal surfaces of the lung after aerosol deposition could improve dosing uniformity and increase the treated area. Our previous studies demonstrated that surfactant additives can produce surface tension-driven (Marangoni) flows that effectively dispersed aerosol-delivered drugs over mucus surfaces. Here we sought to determine whether the addition of a surfactant would increase transport of an aerosol between lung regions and also improve dosing uniformity in human lungs. Methods: We compared the deposition and postdeposition dispersion of surfactant (10 mg/mL dipalmitoylphosphatidylcholine; DPPC) and saline-based liquid aerosols, admixed with Technetium 99m (Tc99m) diethylenetriaminepentaacetic acid, using gamma scintigraphy. Deposition images were obtained ex vivo in eight pairs of ventilated human lungs. The trachea was intubated and the mainstem bronchi were alternately clamped so that saline was delivered to one lung and then DPPC to the other (sides alternated). The lungs were continually imaged for 15 minutes during delivery. We assessed transport of the deposited aerosol by quantifying the percentage of Tc99m in each of four lung quadrants over time. We quantified dose uniformity within each lung quadrant by measuring the coefficient of variation (CV = standard deviation of the pixel associated radioactive counts/mean of the counts within each quadrant). Results: There was no change in the percentage of Tc99m in each quadrant over time, indicating no improvement in transport with the addition of the surfactant. The addition of surfactant was associated with a statistically significant decrease in CV in the lower inner lung quadrant at each of the three time points, indicating an improvement in dosing uniformity. Conclusion: These preliminary results indicate the possible utility of adding surfactant to aerosols to improve drug distribution uniformity to lower inner lung regions.