Preferred Route Research Articles

AN OVERVIEW: DEVELOPMENT OF COLON DRUG DELIVERY SYSTEM AND ITS APPLICATION AND LIMITATIONS

There are various routes of drug administration. Oral administration is considered the most preferred route in drug administration for systemic effects, but the oral administration is not suitable for people with ulcerative colitis, crohn's disease, bowel cancer, diarrhea, treatment of diseases that sensitive to circadian rhythms such as asthma and angina, as well as for steroids administration. The delivery of targeted drugs has the goal of achieving the desired therapeutic profile by delivering the drug to the target site. This study conducted by reviewing related articles based on specify keywords on Science Direct database that has been published for the last 10 y. In recent decades, research has been conducted to develop methods that can target drugs to specific organs. The focusing on targeted drug delivery system to the colon, the various ways that were carried out for its approach, as well as the evaluation. By this study, some challenges in the colon drug delivery system could be overcome along with new approaches.

PREOPERATIVE ANALYTICAL PREDICTORS OF COMPLICATED ACUTE APPENDICITIS MYTH OR REALITY OF PREDICTIVE SCORES?

Abstract Introduction Acute appendicitis (AA) is the most frequent surgical emergency. Clinical and analytical parameters are the diagnostic basis. We analyze the predictive value of inflammatory markers (IM) and their relationship with complicated appendicitis (cAA), identifying a predictive SCORE. Methods Retrospective observational analysis of 484 patients > 14 years operated on for AA at a tertiary center between 2017–2019. 2 groups according to intraoperative findings in complicated and uncomplicated appendicitis (ncAA). Univariate logistic regression analysis was performed to evaluate the predictive ability of leukocyte count (LC), percentage of neutrophils (PN), CRP and polyglobulia) creating a multivariable predictive model. Results 83.7% <65 years, with ultrasonography being the most frequent diagnostic study and laparoscopy the preferred route of approach. 43.30% (207) complicated vs 54.81% (262) uncomplicated. Both LC and PN and CRP present statistically significant associations with complicated appendicitis, with a cut-off point of LC >18,990, PN >61.8% and CRP >5.05 respectively, while polyglobulia is related to less complication OR 0.63% (p 0.01402). According to the multivariable model 1/ [1 + e - (- 4.45–0.000003 * leukocytes + 0.043 * neutrophil percentage + 0.138 * CRP - 0.028 (if red series anemia) - 1.031 (if red series polyglobulia))] good predictive capacity is evidenced. Harrel's C corrected index of 0.743 CI95% (0.69%-0.78%). Conclusions Elevation of IM is associated with cAA. The predictive ability of the described SCORE is acceptable, and useful in surgical planning. Prospective validation is needed.

Ab initio chemical kinetics of Isopropyl acetate oxidation with OH radicals

ABSTRACT Global reactivity descriptors of isopropyl acetate (IPA) and thermo-kinetic aspects of its oxidation via OH radicals have been studied. Transition state theory (TST) was utilized to estimate the bimolecular rate constants. Ten oxidation pathways have been investigated, and all of them are exothermic. The potential energy diagram has been sketched using different pre- and post-reactive complexes for all reaction pathways. Rate coefficient calculations were obtained directly by connecting the separated reactants with different transition states. The results indicate that the reaction of IPA with OH radicals occurs in the ground state rather than the excited state, and the rate constants obtained directly and from the effective approach are the same, which confirmed the accuracy of the estimated pre-reactive complexes and the reaction mechanism. Rate constants and branching ratios show that hydrogen atom abstraction from the iso C − H (C2 atom) bond is the most kinetically preferable route up to 1000 K, while at higher temperatures, H-atom abstraction from the out-of-plane CH3 group (C3 atom) became the most dominant route with high competition with that of the in-plane CH3 group (C4 atom).

A prospective comparative study of 3 different regimens involving mifepristone and oral/ vaginalmisoprostol combination in medical termination of pregnancy at less than 9 weeks gestation

Background and Objectives: Medical abortion with a combination of mifepristone and a prostaglandin analogue (Misoprostol) is a well-established and adequately studied as an alternative to surgical abortion in early pregnancy for many years now but still no consensus has been reached regarding superiority of one route and dosage. This study is an attempt to compare efficacy in terms of rate of complete abortion, side effects and women’s perceptions of three mifepristone/misoprostol regimens and to study the effect of continued oral misoprostol for one week in medical termination of pregnancies of less than nine weeks gestation. Materials and Methods: Abortion seeking women of less than nine weeks period of gestation were included in this study and were divided into three groups: GROUP I also referred as O+O group, GROUP II the V+O group, and GROUP III referred as V ONLY group. This is an outpatient regimen requiring minimum three visits on day 1, 3 and 15. Initially, tablet mifepristone 200 mg was administered orally in all three groups on day 1. This was followed on day 3 by oral misoprostol 0.8 mg in group I and vaginal 0.8 mg misoprostol in group II & III. It was placebo controlled. Patients were sent home after 4 hour observation period. The oral group and one of the vaginal groups i.e. group I and II continued 0.4 mg of oral misoprostol twice daily for 7 days. Final assessment was done on day 15. Results: All three groups were comparable in terms of rates of complete abortion: Group I 93.06%; II 94.44% and group III 93.06%. Incomplete abortion occurred in 9.72% women in group I, 5.52% in group II and 6.94% women in group III. 73.61 % of women in group I, 76.38% women in group II and 77.76% in group III suffered from lower abdominal pain & cramping. 100% women cited oral route as their preferred route and overall 199 (92%) women were satisfied with treatment, 12(5.6%) were unsure and 5(2.4%) were dissatisfied. For future purposes 100 % women cited medical abortion to be their preferred mode compared to surgical one Conclusion: In light of previous studies establishing superiority of vaginal route over oral, continuation of misoprostol for 7 days possibly improved the efficacy for oral misoprostol group(group I) but it did not seem to further increase the efficacy for vaginal Misoprostol (group II) as all three groups were of comparable efficacy. Additional misoprostol did not shorten the duration of bleeding or induction abortion interval compared to group not continuing additional one week misoprostol. Successful abortion was associated more with lower gestational age,multigravidas and multiparas.Oral group had higher frequency of nausea, vomiting and diarrhea than vaginal administration. Statistically insignificant but still lower number of women were satisfied in the end with the treatment in the oral group compared to vaginal groups despite oral mode being the preferred mode. Additional larger studies are required on initial oral misoprostol administration and its continuation to establish its equivalence to vaginal route.

Surgical Morbidity of Laparoscopic Hysterectomy versus Abdominal Hysterectomy: A Retrospective Overview.

Laparoscopic skills are not an innate behavior, nor can they be easily mimicked, and can only be acquired through hands-on training. The need for reliable training and its assessment is becoming increasingly important with the course of time. A retrospective comparative study was done in a tertiary care center where all patients undergoing hysterectomy by laparoscopic and abdominal route were included in the study. Our study aims to compare the operative and postoperative complications of laparoscopic hysterectomy with abdominal hysterectomy. The study was conducted from June 2016 to October 2022. The mean operative time for uteri size lesser than 12 weeks was found significant in the total laparoscopic hysterectomy (TLH) group (75 ± 25 min) to total abdominal hysterectomy (TAH) (117 ± 28 min, P < 0.001). The mean blood loss in the TLH group was significant (110 ± 30 ml vs. 160 ± 116 ml, P < 0.002). The mean hospital stay was significantly shorter in TLH (4 ± 2.4 days vs. 7 ± 2.41 days, P < 0.002). The operative and postoperative complications observed were 3.1% in the TLH group and 11.7% in the TAH group. TLH when performed efficiently has proved to be a preferable route over other conventional hysterectomies.

Xylose dehydration to furfural using niobium doped δ-FeOOH as catalyst

The effect of modification of ?-FeOOH with niobium, applied to dehydration reaction of xylose, was evaluated by experimental and theoretical methods. The experimental data confirmed, namely the characteristic peaks in the X-ray diffractometer analysis, that the materials were obtained. Inductively coupled plasma mass spectrometry analysis defined the percentage of Nb as 0 for pure ?-FeOOH and 9.5 wt. % (?-FeOOH/Nb) for doped. In relation to obtaining furfural, the doped material presents a conversion improvement of 290 % when compared to pure catalyst. Theoretical calculations were useful in understanding the preferential route of the mechanisms proposed by the obtained potential energy values. To understand the preferred routes, the most favorable position of xylose in relation to ?-FeOOH was initially calculated. From this, the conditions favoring furfural formation were calculated based on the routes of the proposed mechanisms and the energy values indicated that the furfural formation is more likely to happen on the doped material.

Buccal Versus Vaginal Misoprostol Combined with a Foley Catheter Among Individuals with Obesity Undergoing Induction

Combining pharmacologic agents with mechanical ripening achieves the shortest labor, yet there is no clear evidence on route of drug administration in patients with obesity. Our objective was to evaluate the difference in time to delivery of buccal compared to vaginal misoprostol in combination with a Foley catheter (FC) for labor induction (IOL) in the obese population. This was a planned secondary analysis of a randomized controlled trial comparing identical dosages (25μg) of buccal and vaginal misoprostol in combination with a FC. Labor management was standardized among participants. Women undergoing IOL at ≥37 weeks with a singleton gestation and cervical dilation ≤2cm were included. Body mass index (BMI, kg/m2) was stratified. Our primary outcome was time to delivery. Kruskal-Wallis, Pearson chi-square and Cox survival analyses with intent-to-treat principles were performed. 215 participants were included with the following weight stratifications: 55 (25.6%) BMI < 30; 110 (51.2%) BMI 30-39.9; 50 (23.3%) BMI ≥40. Demographic characteristics were similar between the three groups. Vaginal drug administration achieved a faster median time to delivery than the buccal route among patients with a BMI range of 30-39.9, (vaginal miso–FC: 21.3hrs vs. buccal miso–FC: 23.6hrs, p=0.04). There was no difference in the cesarean delivery rate between the various groups. Furthermore, patients with a BMI range of 30-39.9 receiving vaginal misoprostol delivered 1.2 times faster than women who received buccal misoprostol after censoring for Cesarean delivery and adjusting for parity, (Hazard Ratio [HR] 1.2, 95% confidence interval [CI] 1.1-1.7). There were no significant differences in maternal and neonatal outcomes. We found that vaginal misoprostol was superior to buccal misoprostol when combined with a FC among individuals with a BMI range of 30-39.9. Therefore, vaginal misoprostol should be the preferred route of drug administration for term IOL in this population.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Prevalence of non-adherence to medications in people with type 2 Diabetes mellitus

Diabetes mellitus (DM) is a chronic, non-communicable disease that has an increasing incidence rate over time as well as increasing disease-related deaths. Furthermore, around half of diabetic patients are unaware actually about their disease, and more are not taking their medications. This study aimed to determine the extent of medication adherence and factors contributing to non-adherence among diabetic patients in Majmaah governance, Saudi Arabia. This is an observational cross-sectional study design conducted among patients with type 2 diabetes. A self- administered questionnaire was distributed among diabetic patients .The questionnaire consisted of socio- demographic data, HbA1c level, duration of DM, family history of DM, DM medications and 12-Item Medication Adherence Scale. 180 patients with diabetes type 2 were involved (71.7% females vs. 28.3% males). The prevalence of patients with uncontrolled HbA1c levels was 25%. Family history of DM constitutes 74.4%. The most preferred route for drug administration was oral (50.6%). High non-adherent to medication was found among 57.8%. The independent significant factor associated with high non-adherence to DM medication was uncontrolled HbA1c while being a female was the independent significant factor for low non-adherent to DM medication. The non-adherent of the diabetic patients regarding anti-diabetes medications was widely prevalent. Female patients tend to be more adherent to DM medication than their male counterparts. This study established the fact that uncontrolled glycated hemoglobin was a detrimental factor in adherence to anti-DM medications. More studies are required to raise the awareness of the diabetic population regarding the importance of medication adherence.

Current Prescribing Practices in Bacterial Skin Infections in a Tertiary care hospital- A Prospective study

Background: Skin diseases of microbial etiology are caused by bacteria, fungi, viruses, and ectoparasites, of which bacterial infections are most common than others. Antibiotic resistance among the micro-organisms is developing due to indiscriminate use of antibiotics and irrational prescription of drugs. Aims and Objectives: The aims of this study were to assess various aspects of prescription pattern and rational use of antibiotics for bacterial infections in the department of dermatology. Materials and Methods: A prospective analysis of 120 patients attending Dermatology Out Patient Department, at Government Medical College, Srikakulam, for 16 months (June 2017–September 2018) was carried out to analyze the usage of antibiotics through various routes to treat dermatological infections. The number of antibiotics prescribed, their name, class of drug, frequency and route of administration, and duration were recorded and analyzed using descriptive statistics. Results: Among the study population, 55.9% were male and 44.1% were female. Acne vulgaris (25%) is the most common condition, for which antibiotics were prescribed followed by impetigo (16.66%). Most commonly prescribed systemic antibiotics were penicillins (51.66%) followed by macrolides (18.33%). Most commonly prescribed topical antibiotic was mupirocin (33.33%) followed by clindamycin (25%). The most preferred route of antibiotic administration was oral route (62.44%). Conclusion: Prescription pattern of antibiotics in this study proved that dermatologists followed rationality and contributed their part to curb the spread of antibiotic resistance. Periodic screening of drug prescribing pattern studies should be done to rationalize the prescription, to reduce errors, and to increase therapeutic benefits and cost-effective management.

Insulin-loaded liposomes packaged in alginate hydrogels promote the oral bioavailability of insulin.

Compared to subcutaneous injections, oral administration of insulin would be a preferred route of drug administration for diabetic patients. For oral delivery, both liposomes and alginate hydrogels face many challenges, including early burst release of the encapsulated drug and poor intestinal drug absorption. Also, adhesion to the intestinal mucosa remains weak, which all result in a low bioavailability of the payload. This study reports on an alginate hydrogel loaded with liposomes for oral insulin administration. Liposomes (Lip) loaded with arginine-insulin complexes (AINS) were incorporated into a hydrogel prepared from cysteine modified alginate (Cys-Alg) to form liposome-in-alginate hydrogels (AINS-Lip-Gel). An ex vivo study proves that intestinal permeation of AINS and AINS-Lip is approximately 2.0 and 6.0-fold, respectively, higher than that of free insulin. The hydrogel retarded early release of insulin (∼30%) from the liposomes and enhanced the intestinal mucosal retention. In vivo experiments revealed that the AINS-Lip-Gel released insulin in a controlled manner and possessed strong hypoglycemic effects. We conclude that liposome-in-alginate hydrogels loaded with AINS represent an attractive strategy for the oral delivery of insulin.

Primary pituitary tuberculosis: A rare clinical entity.

Primary pituitary tuberculosis: A rare clinical entity.

Design and characterization of lipid nanocarriers for oral delivery of immunotherapeutic peptides.

The use of therapeutic proteins and peptides is of great interest for the treatment of many diseases, and advances in nanotechnology offer a path toward their stable delivery via preferred routes of administration. In this study, we sought to design and formulate a nanostructured lipid carrier (NLC) containing a nominal antigen (insulin peptide) for oral delivery. We utilized the design of experiments (DOE) statistical method to determine the dependencies of formulation variables on physicochemical particle characteristics including particle size, polydispersity (PDI), melting point, and latent heat of melting. The particles were determined to be non-toxic in vitro, readily taken up by primary immune cells, and found to accumulate in regional lymph nodes following oral administration. We believe that this platform technology could be broadly useful for the treatment of autoimmune diseases by supporting the development of oral delivery-based antigen specific immunotherapies.

To Explore the Effect of Modified Seashell on the Thermo-Mechanical Properties of Polymer Matrix Composite

This research paper proposes a sustainable and feasible technique to utilize seashell waste. The utilization of seashells offers economic and environmental benefits because of their abundant, renewable, and cheap source of calcium carbonate. The technique will reduce the hazards of seashell waste generated to the environment and landfilling that cause risk to water sources and public health. Moreover, the synthesized bio − CaCO3 will reduce the end-product cost of the polymer. The successful synthesis of bio-calcium carbonate powder (bio − CaCO3) was carried out using a calcinations technique up to 800°C from seashells. The high density polyethylene (HDPE) composite samples were prepared via the industrially preferred melt route by varying the shell powder content by 10% and 20% by weight. The composite was subjected to Thermal Gravimetric Analysis (TGA), Differential Scanning Calorimetric (DSC), and mechanical analysis. TGA confirmed the thermal behavior of synthesized bio − CaCO3. The thermal degradation temperature of bio − CaCO3 and virgin HDPE were distinctly observed at 734 °C and 443 °C, respectively, in composite samples. The thermal stability was increased by more than 37 °C in the composite sample at 20% bio − CaCO3 loadings. The percent crystallinity also increased by 14% for higher bio − CaCO3 loadings when compared to virgin HDPE. DSC analysis showed no significant changes in melting points and was not affected by the addition of bio − CaCO3 and remained at about 134 °C in virgin and composite samples. This observation is attributed to the similar crystal structures in all samples. The HDPE composite sample showed higher tensilestrength, about 25%, than virgin HDPE. In addition, HDPE10 and HDPE20 composite samples showed lowerelongation at break when compared to virgin HDPE in accordance with the literature.

Formulation Optimization and Evaluation of Orally Disintegrating Tablets of Moxifloxacin

Oral administration of a pharmacologically active agent is the common and most preferred route among patients suffering from different types of illness. In the market, different type of oral dosage form is available among them tablet is the most favorite and demanded formulation. Further, the tablets, which are easy to use and swallow, are the ideal dosage form like orally disintegrating tablets (ODT’s). The main advantage of this type of formulation is that they can give easily to old aged and under-aged patients. In this research work, ODT’s formulation was manufactured, which get easily disintegrates and gives no bitter taste in the buccal cavity during administration. To achieve this task, moxifloxacin was complexed with suitable ion exchange resins (IER) like Kyron T314. In this course of action, multiple trials were performed using variable percentages or ratio of moxifloxacin and Kyron T 314. The resulting complex powder was characterized by different parameters like IR spectroscopy and differential scanning calorimetry (DSC). Along with the other excipients, drug resin complex (DRC) was used to manufacture the tablets. In this process, two super disintegrants viz. cross povidone and Ac di sol were used, and tablets were prepared by direct compression methodology. The finished product parameters of the tablet were estimated using the different available analytical methodologies. In this research work, it was concluded that the minimum time (19 seconds) for the wetting of tablets was observed when the quantity of crospovidone used was around 10% (MIT05). Additionally, this formulation gives maximum drug release (84.48%) after 120 minutes. Therefore, by using a suitable IER, taste-masked ODT’s of moxifloxacin can be prepared. This method is more efficient and effective in the development of such type of formulations.

Nutritional Management of Intestinal Failure due to Short Bowel Syndrome in Children.

The most common cause of intestinal failure (IF) in childhood remains short bowel syndrome (SBS), where bowel mass is significantly reduced due to a congenital atresia or resection and parenteral nutrition (PN) needed. Home PN has improved outcome and quality of life, but the long-term therapeutic goal is to achieve enteral autonomy whilst avoiding long term complications. This paper is aimed at discussing nutritional strategies available to clinicians caring for these patients. A literature search was performed from 1992 to 2022 using Pubmed, MEDLINE and Cochrane Database of Systematic Reviews, and recent guidelines were reviewed. In the absence of evidence, recommendations reflect the authors' expert opinion. Consensus on the best possible way of feeding children with IF-SBS is lacking and practice varies widely between centres. Feeding should commence as soon as possible following surgery. Oral feeding is the preferred route and breast milk (BM) the first milk of choice in infants. Donor BM, standard preterm or term formula are alternatives in the absence of maternal BM. Extensively hydrolysed or amino acid-based feeds are used when these are not tolerated. Solids should be introduced as soon as clinically appropriate. Children are encouraged to eat by mouth and experience different tastes and textures to avoid oral aversion. Aggressive weaning of PN and tube (over-) feeding are now discouraged. To date, uniform agreement on the optimal type of feed, timing of food introduction and feeding regime used is lacking and great difference in practice remains. There is need for more research to establish common treatment protocols.

1058. Development of a Steroid Stewardship Bundle to tackle the Glucocorticoid-Induced Hyperglycemia in COVID-19 patients: Results of SUPER Diabetes Study.

Abstract Background Glucocorticoid therapy in COVID-19 patients poses a greater risk of hyperglycemia, leading to an unexpected detrimental effect on treatment outcomes. The Steroid Use in Patients Exhibiting Risk (SUPER) to Diabetes -SUPER Diabetes- study aimed to implement a steroid stewardship bundle to encounter the incidence of Glucocorticoid-Induced Hyperglycemia (GCIH) in COVID-19 patients and to evaluate the effectiveness of the Steroid Stewardship Program. Methods This interventional study included 600 COVID-19 confirmed patients admitted between April 2021and March 2022 in a secondary care hospital in India (stewardship cohort). A six-item Steroid Appropriate Index (SAI) assessed the need for steroid therapy using the parameters like the severity of disease, the onset of symptoms, weight of the patient, CT Thorax score, the preferred route of administration, and the comorbid disorders. This created a steroid stewardship bundle with the following parameters: (1) appropriate selection of the corticosteroid; (2) repeat blood sugar monitoring every 8 hours until discharge from hospital; (3) appropriate duration of therapy (4) proper de-escalation of dose/intravenous to oral switch. The patients were followed until discharge/death to track the incidence of hyperglycemia. The analysis of the effectiveness of SAI and the stewardship bundle was done by comparing this with the clinical outcomes among 300 COVID-19 confirmed patients admitted before implementing the scale (retrospective cohort). Results The majority of the patients included in the stewardship cohort were males (367; 61.1%), and the mean age was 47.3± 17.1 years. The incidence of new-onset of hyperglycemia or a worsened glycemic profile, i.e., Glucocorticoid-Induced Hyperglycemia (GCIH), was more among the retrospective cohort when compared with the stewardship cohort (32.1% vs 6.3%), p&amp;lt; 0.001). The study also revealed that history of diabetes (p&amp;lt; 0.001), age (p=0.002), number of medicines used for treatment (p&amp;lt; 0.001), and the frequency of monitoring of diabetes (p&amp;lt; 0.001) are significantly associated with GCIH. Conclusion Implementing the steroid stewardship bundle significantly improved the appropriate selection and use of corticosteroids, decreasing the incidence of associated adverse events. Disclosures All Authors: No reported disclosures.

Attitudes of Community Pharmacy Service Users towards Vaccination Programs in Pharmacy: A Cross-Sectional Survey-Based Study in Croatia.

The aim of this study was to explore community pharmacy service users' attitudes and opinions towards vaccination programs in pharmacy conducted by a doctor of medicine or a pharmacist. The questionnaire used in this study comprised 40 items about demographics, sources of information, attitudes about vaccination, attitudes about vaccination in community pharmacies, and willingness to pay for such a service. A total of 385 people participated in this study. Injection was the preferred route of administration of vaccine for more than half of study participants (50.6%). Univariate analysis showed that those who had a healthcare worker as a family member and those familiar with the HPV vaccine had better attitudes; however, those results were no longer significant after factoring in other variables in multivariate analysis. More than half (59.2%) of the study population would consider vaccination service in community pharmacies only if it were free or covered by the national health insurance. More than half of the participants believed that providing vaccination services in community pharmacies would result in greater vaccination rates for seasonal illnesses. However, around half would prefer that it were conducted exclusively by a physician. Less than 10% of the study participants would pay out of their pocket for such a service.

Microwave-boosted elemental mercury removal using natural low-grade pyrolusite

Utilizing natural minerals to remove Hg0 from flue gas was regarded as a preferable route to control mercury pollution. This paper purposed a novel microwave (MW)-boosted removal method using natural low-grade pyrolusite (NLP), by which over 85 % of Hg0 was removed and approximately 10–20 % of the increment of efficiency was obtained. Compared with thermo-catalysis, MW also empowered NLP with a wider active-temperature range (100–250 °C) and better H2O and SO2 resistances. Kinetic analysis showed that MW increased the rate constant and reduced the activation energy, Hg-TPD and material balance analyses demonstrated that major Hg0 was chemisorbed as HgO. Via the thermal treatment experiments, the regeneration performance of NLP was confirmed to be good. From the experiments and characterizations, the mechanism was preliminarily speculated: (i) the contribution order of the active components was MnO2 > Mn3O4 > Fe2O3; (ii) the redox pairs of Fe(II)/Fe(III) and Mn(III)/Mn(IV), as well as the O-species, involved in the conversion from Hg0 to HgO. Density functional theory calculations revealed the pathway and mechanism: (i) MnO2 exhibited higher oxidation activity, whereas Mn3O4 showed higher adsorption activity; (ii) Odis derived from Oads enhanced the removal of Hg0 by increasing the adsorption energies and amounts of transferred electron; (iii) Oads had advantages over Olat in term of desorbing HgO, which was the rate-determining step.

Novel trehalose-based excipients for stabilizing nebulized anti-SARS-CoV-2 antibody

COVID-19 is caused by the infection of the lungs by SARS-CoV-2. Monoclonal antibodies, such as sotrovimab, showed great efficiency in neutralizing the virus before its internalization by lung epithelial cells. However, parenteral routes are still the preferred route of administration, even for local infections, which requires injection of high doses of antibody to reach efficacious concentrations in the lungs. Lung administration of antibodies would be more relevant requiring lower doses, thus reducing the costs and the side effects. But aerosolization of therapeutic proteins is very challenging, as the different processes available are harsh and trigger protein aggregation and conformational changes. This decreases the efficiency of the treatment, and can increase its immunogenicity.To address those issues, we developed a series of new excipients composed of a trehalose core, a succinyl side chain and a hydrophobic carbon chain (from 8 to 16 carbons). Succinylation increased the solubility of the excipients, allowing their use at relevant concentrations for protein stabilization. In particular, the excipient with 16 carbons (C16TreSuc) used at 5.6 mM was able to preserve colloidal stability and antigen-binding ability of sotrovimab during the nebulization process. It could also be used as a cryoprotectant, allowing storage of sotrovimab in a lyophilized form during weeks. Finally, we demonstrated that C16TreSuc could be used as an excipient to stabilize antibodies for the treatment against COVID-19, by in vitro and in vivo assays. The presence of C16TreSuc during nebulization preserved the neutralization capacity of sotrovimab against SARS-CoV-2 in vitro; an increase of its efficacy was even observed, compared to the non-nebulized control. The in vivo study also showed the wide distribution of sotrovimab in mice lungs, after nebulization with 5.6 mM of excipient.This work brings a solution to stabilize therapeutic proteins during storage and nebulization, making pulmonary immunotherapy possible in the treatment of COVID-19 and other lung diseases.

Colon Targeting: A Novel Drug Delivery System

The oral route is considered to be the most preferred route for administration of drugs for systemic effect, but the oral route is not suitable to the administration of drug for lower gastrointestinal (GI) diseases, this happened due to their release at upper GI tract (stomach, small intestine), which further minimizes the accessibility of drugs at the lower GI tract. To overcome this difficulty, colon-specific drug delivery systems have been broadly analyzed during the last two decades. Colonic drug delivery has gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon like Crohn’s disease, ulcerative colitis, etc. but also for the systemic delivery of proteins, therapeutic peptides, anti-asthmatic drugs, antihypertensive drugs, and anti-diabetic agents. This review article discusses, in brief, the introduction of the colon, factor affecting the colonic transition, colonic diseases and the novel and emerging technologies for colon targeting.