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International Journal of Pharmaceutics:... Dec 2023Infliximab is a monoclonal antibody that plays an important role in the management and treatment of chronic inflammatory bowel diseases (IBD). Due to its macromolecular...
Infliximab is a monoclonal antibody that plays an important role in the management and treatment of chronic inflammatory bowel diseases (IBD). Due to its macromolecular structure, its delivery through the oral route is challenging, limiting its administration to only via the parenteral route. The rectal route offers an alternative way for administering infliximab, allowing it to be localised at the disease site and circumventing its passage across the alimentary canal and thus, maintaining its integrity and bioactivity. Three-dimensional (3D) printing is an advanced production technology that permits the creation of dose-flexible drug products from digital designs. The current study assessed the feasibility of utilising semi-solid extrusion 3D printing for the fabrication of infliximab-loaded suppositories for the local treatment of IBD. Various printing inks composed of Gelucire® (48/16 or 44/14) mixed with coconut oil and/or purified water were investigated. It was shown that following reconstitution in water, the infliximab solution can be directly incorporated into the printing ink of Gelucire® 48/16 and can withstand the extrusion process, resulting in well-defined suppositories. Since water content and temperature are critical for safeguarding infliximab's potency, the effect of changing the composition of the printing inks and printing parameters on infliximab's biologic efficiency was evaluated by measuring its binding capacity (i.e., the amount of infliximab that actively binds to its antigen to exert an effect). Despite drug loading assays showing that infliximab remains intact following printing, it was found that the incorporation of water in isolation results in only ∼65% binding capacity. However, when oil is added to the mixture, infliximab's binding capacity increases up to ∼85%. These promising results demonstrate that 3D printing has the potential to be exploited as a novel platform for fabricating dosage forms containing biopharmaceuticals, avoiding patients' compliance issues observed with injectables and addressing their unmet needs.
PubMed: 37396625
DOI: 10.1016/j.ijpx.2023.100176 -
International Journal of Molecular... May 2021Rectal drug delivery is an effective alternative to oral and parenteral treatments. This route allows for both local and systemic drug therapy. Traditional rectal dosage... (Review)
Review
Rectal drug delivery is an effective alternative to oral and parenteral treatments. This route allows for both local and systemic drug therapy. Traditional rectal dosage formulations have historically been used for localised treatments, including laxatives, hemorrhoid therapy and antipyretics. However, this form of drug dosage often feels alien and uncomfortable to a patient, encouraging refusal. The limitations of conventional solid suppositories can be overcome by creating a thermosensitive liquid suppository. Unfortunately, there are currently only a few studies describing their use in therapy. However, recent trends indicate an increase in the development of this modern therapeutic system. This review introduces a novel rectal drug delivery system with the goal of summarising recent developments in thermosensitive liquid suppositories for analgesic, anticancer, antiemetic, antihypertensive, psychiatric, antiallergic, anaesthetic, antimalarial drugs and insulin. The report also presents the impact of various types of components and their concentration on the properties of this rectal dosage form. Further research into such formulations is certainly needed in order to meet the high demand for modern, efficient rectal gelling systems. Continued research and development in this field would undoubtedly further reveal the hidden potential of rectal drug delivery systems.
Topics: Acrylic Resins; Administration, Rectal; Alginates; Body Temperature; Drug Compounding; Drug Delivery Systems; Forecasting; Gels; Hot Temperature; Humans; Intestinal Absorption; Methylcellulose; Pharmaceutical Preparations; Poloxamer; Povidone; Suppositories
PubMed: 34071110
DOI: 10.3390/ijms22115500 -
Pancreatology : Official Journal of the... Nov 2023There is an unmet clinical need for effective, targeted interventions to prevent post-ERCP pancreatitis (PEP). We previously demonstrated that the serine-threonine...
OBJECTIVE
There is an unmet clinical need for effective, targeted interventions to prevent post-ERCP pancreatitis (PEP). We previously demonstrated that the serine-threonine phosphatase, calcineurin (Cn) is a critical mediator of PEP and that the FDA-approved calcineurin inhibitors, tacrolimus (Tac) or cyclosporine A, prevented PEP. Our recent observations in preclinical PEP models demonstrating that Cn deletion in both pancreatic and hematopoietic compartments is required for maximal pancreas protection, highlighted the need to target both systemic and pancreas-specific Cn signaling. We hypothesized that rectal administration of Tac would effectively mitigate PEP by ensuring systemic and pancreatic bioavailability of Tac. We have tested the efficacy of rectal Tac in a preclinical PEP model and in cerulein-induced experimental pancreatitis.
METHODS
C57BL/6 mice underwent ductal cannulation with saline infusion to simulate pressure-induced PEP or were given seven, hourly, cerulein injections to induce pancreatitis. To test the efficacy of rectal Tac in pancreatitis prevention, a rectal Tac suppository (1 mg/kg) was administered 10 min prior to cannulation or first cerulein injection. Histological and biochemical indicators of pancreatitis were evaluated post-treatment. Pharmacokinetic parameters of Tac in the blood after rectal delivery compared to intravenous and intragastric administration was evaluated.
RESULTS
Rectal Tac was effective in reducing pancreatic injury and inflammation in both PEP and cerulein models. Pharmacokinetic studies revealed that the rectal administration of Tac helped achieve optimal blood levels of Tac over an extended time compared to intravenous or intragastric delivery.
CONCLUSION
Our results underscore the effectiveness and clinical utility of rectal Tac for PEP prophylaxis.
Topics: Animals; Mice; Administration, Rectal; Anti-Inflammatory Agents, Non-Steroidal; Ceruletide; Cholangiopancreatography, Endoscopic Retrograde; Mice, Inbred C57BL; Pancreatitis; Tacrolimus
PubMed: 37778935
DOI: 10.1016/j.pan.2023.09.080 -
Journal of Drug Delivery Science and... Feb 2021We herein disclose how global cyclodextrin-based pharmaceutical technologies have evolved since the early 80s through a 1998 patents dataset retrieved from Derwent... (Review)
Review
We herein disclose how global cyclodextrin-based pharmaceutical technologies have evolved since the early 80s through a 1998 patents dataset retrieved from Derwent Innovation Index. We used text-mining techniques based on the patents semantic content to extract the knowledge contained therein, to analyze technologies related to the principal attributes of CDs: solubility, stability, and taste-masking enhancement. The majority of CDs pharmaceutical technologies are directed toward parenteral aqueous solutions. The development of oral and ocular formulations is rapidly growing, while technologies for nasal and pulmonary routes are emerging and seem to be promising. Formulations for topical, transdermal, vaginal, and rectal routes do not account for a high number of patents, but they may be hiding a great potential, representing opportunity research areas. Certainly, the progress in materials sciences, supramolecular chemistry, and nanotechnology, will influence the trend of that, apparently neglected, research. The bottom line, CDs pharmaceutical technologies are still increasing, and this trend is expected to continue in the coming years. Patent monitoring allows the identification of relevant technologies and trends to prioritize research, development, and investment in both, academia and industry. We expect the scope of this approach to be applied in the pharmaceutical field beyond CDs technological applications.
PubMed: 33078064
DOI: 10.1016/j.jddst.2020.102156 -
Recent Patents on Nanotechnology 2023To achieve a target-based drug delivery with minimal side effects, novel drug delivery systems are being continuously explored. Vesicular systems are one such system... (Review)
Review
BACKGROUND
To achieve a target-based drug delivery with minimal side effects, novel drug delivery systems are being continuously explored. Vesicular systems are one such system that can ameliorate the bioavailability of the encapsulated drug by delivering the drug at the targeted site and can minimize the side effect.
OBJECTIVE
The objective of this patent review is to provide a vivid description of glycerosomes and their applications. Glycerosomes are sphere-shaped versatile vesicles consisting of one or more phospholipid bilayers similar to liposomes but contain a high concentration of glycerol, which modifies the liposome bilayer fluidity. Glycerosomes can encapsulate both hydrophobic and hydrophilic drugs, which makes them the promising vehicle in the field of drug delivery.
CONCLUSION
Most of the glycerosome formulations prepared were targeted for topical delivery and in particular, a cutaneous route where they have shown promising results. These vesicles are biocompatible and due to the high glycerol concentration, they have improved spreadability and penetrability. It is therefore imperative to explore the other topical routes such as ocular, vaginal, nasal, and rectal for delivery of drugs.
Topics: Administration, Cutaneous; Drug Delivery Systems; Glycerol; Liposomes; Patents as Topic
PubMed: 35346018
DOI: 10.2174/1872210516666220328124450 -
Advanced Science (Weinheim,... Nov 2023Mesenchymal stem cell (MSC) therapy is a promising candidate for inflammatory bowel disease (IBD) treatment, while overcoming the limitations of naive seeding cells...
Mesenchymal stem cell (MSC) therapy is a promising candidate for inflammatory bowel disease (IBD) treatment, while overcoming the limitations of naive seeding cells function and realizing efficient intestinal targeting remains a challenge. Here, a bioadhesive microparticle carrying interleukin-27 (IL-27) MSC-derived extracellular vesicles (MSC EVs) is developed to treat IBD. The MSC EVs prepared through lentivirus-mediated gene transfection technology show ideal anti-inflammatory and damage repair function. By encapsulating MSC EVs into dopamine methacrylamide-modified hydrogel, a bioadhesive EVs microcarrier via microfluidic technology is fabricated. The resultant microcarriers exhibit ideal MSC EVs sustained release effect and effective wet adhesion property. Furthermore, the therapeutic potential of MSC EVs-loaded microcarriers in treating IBD is demonstrated. Through giving IBD rats a rectal administration, it is found that the microcarriers can firmly anchor to the surface of colon, reduce the inflammatory response, and repair the damaged barrier. Therefore, the bioadhesive MSC EVs-loaded microcarriers provide a promising strategy for the biomedical application of MSC-derived EVs, and broaden the clinical potential of MSC therapy.
Topics: Rats; Animals; Interleukin-27; Extracellular Vesicles; Anti-Inflammatory Agents; Inflammatory Bowel Diseases; Mesenchymal Stem Cells
PubMed: 37759399
DOI: 10.1002/advs.202303349 -
Advances in Clinical and Experimental... Dec 2022Anastomotic leakage (AL) following rectal surgery is associated with increased mortality and morbidity. Neoadjuvant radiotherapy disrupts the wound healing process in...
BACKGROUND
Anastomotic leakage (AL) following rectal surgery is associated with increased mortality and morbidity. Neoadjuvant radiotherapy disrupts the wound healing process in rectal surgery.
OBJECTIVES
To evaluate the effects of intra-rectal ozone application on rectal anastomoses after radiotherapy.
MATERIAL AND METHODS
This study was performed on animals. Thirty-two male Wistar rats were randomly divided into 4 groups: control group, ozone group, radiotherapy group, and radiotherapy/ozone group. Ozone was administered intrarectally in the ozone group and water was administered intrarectally in rthe control group for 5 days. The radiotherapy group received 20 Gy of pelvic radiotherapy. The radiotherapy/ozone group received 20 Gy of pelvic radiotherapy after the administration of ozone. Afterward, colon resection followed by an anastomosis were performed under general anesthesia in all groups. Anastomotic segments were resected to evaluate tissue hydroxyproline (HYP) and myeloperoxidase (MPO) levels, perform a histological evaluation, and measure bursting pressure.
RESULTS
There were no statistically significant differences between groups regarding tissue MPO levels (p = 0.55). Tissue HYP levels were significantly decreased in the radiotherapy group (p = 0.04). Bursting pressure was found to be significantly lower in the radiotherapy group (p < 0.05). No significant differences were found between adhesion scores in the control and ozone groups. Exudate formation was significantly lower in the radiotherapy group (p < 0.05). The lowest macrophage scores were found in the radiotherapy group (p < 0.05). Fibroblast scores were the highest in the control group and the lowest in the radiotherapy group (p < 0.05).
CONCLUSIONS
Intra-rectal ozone application significantly improved the anastomotic healing process after radiation exposure.
Topics: Rats; Animals; Male; Rats, Wistar; Colon; Ozone; Wound Healing; Anastomosis, Surgical; Hydroxyproline
PubMed: 36000882
DOI: 10.17219/acem/152121 -
Journal of Virology Apr 2020Zika virus (ZIKV) is a major human pathogen. ZIKV can replicate in female and male reproductive organs, thus facilitating the human-human transmission cycle. Viral...
Zika virus (ZIKV) is a major human pathogen. ZIKV can replicate in female and male reproductive organs, thus facilitating the human-human transmission cycle. Viral shedding in the semen can increase the risk of ZIKV transmission through sexual mode. Therefore, the vaginal and anorectal mucosa are relevant sites for ZIKV infection. However, the pathobiology of ZIKV transmission through the rectal route is not well understood. Here, we utilize a mouse model system to investigate the immunopathological consequences following ZIKV infection of the rectal mucosa compared to a subcutaneous route of infection. We show that ZIKV-rectal inoculation results in viremia with subclinical infection. ZIKV infects the mucosal epithelium and submucosal dendritic cells, inducing immune and inflammatory cell infiltration. Rectal transmission of ZIKV resulted in the generation of serum-neutralizing antibody responses. Mass cytometry analyses of splenocytes showed a significantly reduced level of inflammatory monocyte and neutrophil cellular responses in the rectal route group. Furthermore, immunological priming through the rectal mucosa with an attenuated ZIKV strain resulted in significant protection from lethal subcutaneous ZIKV challenge, further eliciting robust memory CD4-positive (CD4) and CD8 T-cell and ZIKV-specific serum-neutralizing antibody responses. Thus, our study provides deeper immunopathobiological insights on rectal transmission and highlights a rational strategy for mucosal immunization. This model system recapitulates clinical aspects of human ZIKV disease outcome, where most infections are well controlled and result in subclinical and asymptomatic outcomes. Zika virus is a clinically significant human pathogen that is primarily transmitted and spread by species mosquitoes but is also sexually transmissible. The recent pandemic in the Americas led to an unprecedented increase of newborn babies with developmental brain and eye abnormalities. To date, there is no licensed vaccine or therapeutic intervention available for the fight against ZIKV. Understanding the sexual transmission of ZIKV through vaginal and rectal routes is necessary to restrict virus transmission and spread. This study examines the early immunological and pathological consequences of rectal and subcutaneous routes of ZIKV infection using a mouse model. We characterized the primary target cells of ZIKV infection and the subsequent mucosal immune responses to infection, and we demonstrate the protective effect of mucosal rectal immunization using an attenuated ZIKV strain. This mucosal vaccination approach can be further developed to prevent future ZIKV outbreaks.
Topics: Aedes; Animals; Antibodies, Neutralizing; Antibodies, Viral; Cell Line; Chlorocebus aethiops; Disease Models, Animal; Epithelial Cells; Epithelium; Female; Immunity; Immunization; Male; Mice; Mice, Inbred C57BL; Mucous Membrane; Rectum; Semen; T-Lymphocytes; Vaccination; Vero Cells; Zika Virus; Zika Virus Infection
PubMed: 32051274
DOI: 10.1128/JVI.00067-20 -
Expert Review of Anti-infective Therapy Apr 2021Azithromycin was recommended as the first-line therapeutic regimen for treatment of genital infections in men and women by the Centers for Disease Control in 1998. A... (Comparative Study)
Comparative Study Review
INTRODUCTION
Azithromycin was recommended as the first-line therapeutic regimen for treatment of genital infections in men and women by the Centers for Disease Control in 1998. A series of studies of azithromycin for treatment of rectal chlamydial infection in men who have sex with men (MSM) found that azithromycin was significantly less effective than doxycycline.
AREAS COVERED
Literature on treatment of rectal from 2000 through May 2020 was searched using PubMed. Retrospective and observational studies were identified documenting the frequency and treatment of rectal chlamydial infection in MSM, heterosexual men and women that reported lower efficacy of single-dose azithromycin compared to doxycycline. Literature on possible reasons for the lower efficacy were also reviewed including studies of antibiotic resistance, impact of organism load, and persistent infection in rectal specimens and pharmacokinetics and pharmacodynamics of azithromycin in rectal tissue.
EXPERT OPINION
The available data suggests that single-dose azithromycin is not as effective as azithromycin for the treatment of rectal infection in MSM and women. Most of these data have been retrospective or from observational studies. Final recommendations will depend on the outcome of prospective, randomized, treatment studies. We may also need to examine other dosage regimens for azithromycin.
Topics: Anti-Bacterial Agents; Azithromycin; Chlamydia Infections; Chlamydia trachomatis; Doxycycline; Female; Genital Diseases, Female; Genital Diseases, Male; Humans; Male; Rectal Diseases; Sexual and Gender Minorities
PubMed: 33034227
DOI: 10.1080/14787210.2021.1834850 -
Cancer Medicine Oct 2022Antibiotics may alter colorectal cancer (CRC) risk due to gut dysbiosis. We aimed to study the specific and temporal effects of various antibiotics on CRC development in...
BACKGROUND
Antibiotics may alter colorectal cancer (CRC) risk due to gut dysbiosis. We aimed to study the specific and temporal effects of various antibiotics on CRC development in older individuals.
METHODS
This was a territory-wide retrospective cohort study. Subjects aged 60 years and older who did not have CRC diagnosed on screening/diagnostic colonoscopy diagnosed between 2005 and 2013 were recruited. Exclusion criteria were history of CRC, colectomy, inflammatory bowel disease, and CRC diagnosed within 6 months of index colonoscopy. Exposure was use of any antibiotics up to 5 years before colonoscopy. The primary outcomes were CRC diagnosed >6 m after colonoscopy. Covariates were patient demographics, history of colonic polyps/polypectomy, concomitant medication use (NSAIDs, COX-2 inhibitors, aspirin, and statins), and performance of endoscopy centers (colonoscopy volume and polypectomy rate). Stratified analysis was conducted according to nature of antibiotics and location of cancer.
RESULTS
Ninety seven thousand one hundred and sixty-two eligible subjects (with 1026 [1.0%] cases of CRC) were identified, 58,704 (60.4%) of whom were exposed to antibiotics before index colonoscopy. Use of antibiotics was associated with a lower risk of cancer in rectum (adjusted hazard ratio [aHR]: 0.64, 95% CI: 0.54-0.76), but a higher risk of cancer in proximal colon (aHR: 1.63, 95%CI: 1.15-2.32). These effects differed as regards the anti-anaerobic/anti-aerobic activity, narrow-/broad-spectrum, and administration route of antibiotics.
CONCLUSIONS
Antibiotics had divergent effects on CRC development in older subjects, which varied according to the location of cancer, antibiotic class, and administration route.
Topics: Humans; Middle Aged; Aged; Retrospective Studies; Colorectal Neoplasms; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Anti-Bacterial Agents; Cyclooxygenase 2 Inhibitors; Risk Factors; Colonoscopy; Rectal Neoplasms; Aspirin; Anti-Inflammatory Agents, Non-Steroidal; Early Detection of Cancer
PubMed: 35488387
DOI: 10.1002/cam4.4759