Intraperitoneal administration of a thermogel combined with an anticancer agent for the prevention of peritoneal carcinomatosis in a pig model.

Background: Surgeons may discover perioperative clinical situations associated with an increased risk of peritoneal carcinomatosis recurrence after primary resection. We developed a thermogel that can be used as a drug carrier to deliver an anticancer agent in the peritoneal cavity as a rescue solution. The spatial distribution of the thermogel and pharmacokinetics of chemotherapy have been studied in pigs.

Understanding the Impact of Polyunsaturated Fatty Acids on Age-Related Macular Degeneration: A Review.

Age-related Macular Degeneration (AMD) is a multifactorial ocular pathology that destroys the photoreceptors of the macula. Two forms are distinguished, dry and wet AMD, with different pathophysiological mechanisms. Although treatments were shown to be effective in wet AMD, they remain a heavy burden for patients and caregivers, resulting in a lack of patient compliance.

Radiofrequency Combined with Intratumoral Immunotherapy: Preclinical Results and Safety in Metastatic Colorectal Carcinoma.

Radiofrequency ablation (RFA) of cancer induces an anti-tumor immunity, which is insufficient to prevent recurrences. In mice, RFA-intratumoral immunotherapy by granulocyte-macrophage colony-stimulating factor (GM-CSF) and Bacillus Calmette-Guerin resulted in complete metastases regression. Infectious risk in human needs replacement of live vaccines.

Understanding the retention mechanisms of a reversed-phase/anion exchange/cation-exchange column for the separation of epinephrine and norepinephrine.

In this paper, we investigated the retention mechanisms of a reversed-phase/anion-exchange/cation-exchange column (Acclaim trinity P1, Thermo Fisher Scientific) for the separation of epinephrine (EPI) from norepinephrine (NOE). The impact of the acetonitrile (ACN) content, pH, and salt concentration on the retention of these two catecholamines was studied under an isocratic mode with a mobile phase mixture of ACN and ammonium formate or acetate (pH 3 to pH 5). To better understand the retention mechanisms, several retention models were explored, including linear solvent strength, adsorption, quadratic, and mixed-mode models, using various chemical compounds in addition to EPI and NOE.

Exploration of the effects of chloride ions on the analysis of polar compounds at low concentrations by hydrophilic interaction liquid chromatography coupled to a charged aerosol detector: Application to tromethamine.

In this study, we discuss the origin of the slightly increased response of the charged aerosol detector when low-concentration polar drugs formulated with sodium chloride are analyzed by hydrophilic interaction liquid chromatography coupled to the charged aerosol detector. In the case of tromethamine mixed with saline solutions, we investigated several levels including the mobile phase, sample matrix, and detection. We show that the analysis of the rich-salted sample results in both interactions with the mobile phase modifiers and the stationary phase during the run time.

Development of Thermosensitive and Mucoadhesive Hydrogel for Buccal Delivery of ()-Ketamine.

()-ketamine presents potential for the management of acute pain and, more specifically, for the prevention of pain associated with care. However, the administration route can be a source of pain and distress. In this context, a smart formulation of ()-ketamine was designed for buccal administration.

New Preservative-Free Formulation for the Enhanced Ocular Bioavailability of Prostaglandin Analogues in Glaucoma.

Glaucoma is a wide-spread eye disease caused by elevated intraocular pressure. Uncontrolled, this pressure may lead to damages to the optic nerve. Prostaglandin analogues, such as latanoprost and travoprost (which are water-insoluble active substances), are the most used class of active pharmaceutical ingredient.

Investigation of hydrophilic interaction liquid chromatography coupled with charged aerosol detector for the analysis of tromethamine.

Tromethamine (TMM), often encountered in a final drug product, exhibits interesting chemical properties as a counter ion, buffer, or active ingredient. European and US pharmacopeias propose titration against hydrogen chloride for TMM assays. However, this method can be a hindrance when using drugs containing low concentrations of TMM in complex buffered formulations.

Stability of Pentobarbital Hydrogel for Rectal Administration in Pediatric Procedural Sedation.

Pentobarbital is a sedative agent to limit children motion during computed tomography or magnetic resonance imaging (MRI) and ensures the successful completion of the imaging procedure. However, data on rectal drug formulation and its stability in practice are not available. The aim of this study was to formulate and evaluate the stability of a ready-to-use rectal pentobarbital gel.

Stability of calcium levofolinate, 5-fluorouracil and oxaliplatin (FOLFOX) mixture.

FOLFOX is the most common chemotherapy combination prescribed in colorectal cancer. It is composed of calcium levofolinate, 5-fluorouracil and oxaliplatin which demonstrated synergistic outcome. Nowadays, the lack of all-in-one formulation is due to the chemical composition of the pharmaceutical products and the highly pH-dependent stability of each drug.

Mucoadhesive Poloxamer-Based Hydrogels for the Release of HP-β-CD-Complexed Dexamethasone in the Treatment of Buccal Diseases.

Oral lichen planus (OLP) is an ongoing and chronic inflammatory disease affecting the mucous membrane of the oral cavity. Currently, the treatment of choice consists in the direct application into the buccal cavity of semisolid formulations containing a corticosteroid molecule to decrease inflammatory signs and symptoms. However, this administration route has shown various disadvantages limiting its clinical use and efficacy.

Thermosensitive hydrogels for local delivery of 5-fluorouracil as neoadjuvant or adjuvant therapy in colorectal cancer.

Spurred by high risk for local tumor recurrence and non-specific toxicity of systemic chemotherapy, clinicians have recently granted a growing interest to locoregional therapeutic strategies. In this perspective, we recently developed a multipurpose thermosensitive hydrogel based on reversible thermogelling properties of poloxamers P407 and P188, a bioadhesive excipient and antineoplastic effect of 5-fluorouracil (5-FU) for the local treatment of colorectal cancer (CRC) in ectopic CT26 murine models. Antitumor efficacy was assessed in mice following intratumoral (IT) injection mimicking neoadjuvant therapy and subcutaneous (SC) application after tumor excision simulating adjuvant therapy.

Drug delivery systems to prevent peritoneal metastasis after surgery of digestives or ovarian carcinoma: A review.

Peritoneum represents a frequent site of metastasis especially for digestive and ovarian primary cancers. The conventional approach to treat peritoneal metastasis consists in systemic chemotherapy, but the median survival associated is only a few months. Recent therapeutic developments result in an aggressive strategy associating cytoreductive surgery (CRS) and hyperthermic intra peritoneal chemotherapy (HIPEC).

Acceptability in the Older Population: The Importance of an Appropriate Tablet Size.

Presenting many advantages, solid oral dosage forms (SODFs) are widely manufactured and frequently prescribed in older populations regardless of the specific characteristics of patients. Commonly, patients with dysphagia (swallowing disorders) experience difficulties taking SODFs, which may lead to non-adherence or misuse. SODF characteristics (e.

In Situ Gelling Ophthalmic Drug Delivery System for the Optimization of Diagnostic and Preoperative Mydriasis: In Vitro Drug Release, Cytotoxicity and Mydriasis Pharmacodynamics.

Mydriasis is required prior to many eye examinations and ophthalmic surgeries. Nowadays, phenylephrine hydrochloride (PHE) and tropicamide (TPC) are extensively used to induce mydriasis. Several pharmaceutic dosage forms of these two active ingredients have been described.

Acceptability of oral liquid pharmaceutical products in older adults: palatability and swallowability issues.

Background: In institutional care, oral liquid pharmaceutical products are widely prescribed for older patients, especially for those with swallowing disorders. As medicines acceptability is a key factor for compliance in the older population, this study investigated the acceptability of oral liquid pharmaceutical products in this targeted population.

Methods: An observational, multicenter, prospective study was conducted in eight geriatric hospitals and eight nursing homes in France.

Novel in situ gelling ophthalmic drug delivery system based on gellan gum and hydroxyethylcellulose: Innovative rheological characterization, in vitro and in vivo evidence of a sustained precorneal retention time.

Achieving drug delivery at the ocular level encounters many challenges and obstacles. In situ gelling delivery systems are now widely used for topical ocular administration and recognized as a promising strategy to improve the treatment of a wide range of ocular diseases. The present work describes the formulation and evaluation of a mucoadhesive and ion-activated in situ gelling delivery system based on gellan gum and hydroxyethylcellulose for the delivery of phenylephrine and tropicamide.

Dosage form suitability in vulnerable populations: A focus on paracetamol acceptability from infants to centenarians.

Introduction: Medicine acceptability is a multi-faceted concept driven by both product and user characteristics. Although a key factor for treatment effectiveness, especially in vulnerable populations, knowledge of those medicine features that best promote individual user acceptability remains fragmented. Focusing on paracetamol, this study has explored the appropriateness of pharmaceutical products in different dosage forms to achieve adequate patient acceptability from infants to centenarians.

Sex Differences in Medicine Acceptability: A New Factor to Be Considered in Medicine Formulation.

Palatability is a recognized driver of medicine acceptability in pediatrics but deemed less relevant in older populations due to sensory decline. Preliminary findings from an observational study implicated palatability problems with one Alzheimer's medicine. Among 1517 observer reports combining multiple measures on medicines uses in patients aged over 64, we focused on two original formulations of memantine (Ebixa, tablets ( = 25) and oral solution ( = 60)).

Mucoadhesive thermosensitive hydrogel for the intra-tumoral delivery of immunomodulatory agents, in vivo evidence of adhesion by means of non-invasive imaging techniques.

Intratumoral injection of biocompatible gels is increasingly used for the sustained delivery of drugs and vaccines to enhance the anti-cancer immune response. Granulocyte-macrophage colony stimulating factor (GM-CSF) has become an attractive adjuvant thanks to its ability to boost the antitumor immune response by inducing proliferation, maturation and migration of the dendritic-cells (DCs) and the differentiation of lymphocytes. Killed Mycobacteria, such as Heat-killed Mycobacterium tuberculosis (HKMT) have been used in several studies as TLR-2 agonist to increase maturation of DCs.

Local immunomodulation combined to radiofrequency ablation results in a complete cure of local and distant colorectal carcinoma.

Radiofrequency ablation (RFA) of colorectal liver metastases activates a specific T-cell response that is ineffective in avoiding recurrence. Recently, local immunomodulation garnered interests as a way to improve the immune response. We were interested in improving the RFA immune response priming to propose a curative treatment of colorectal cancer (CRC) based on antitumor immunity.

A Decision Support Tool Facilitating Medicine Design for Optimal Acceptability in The Older Population.

Purpose: Medicine acceptability, which is of the utmost importance for vulnerable patients' adherence, is driven by both user and product characteristics. Herein, a novel multivariate approach integrating the many aspects of acceptability is used to discriminate positively and negatively accepted medicines in the older population.

Methods: An observational study was carried out in eight hospitals and eight nursing homes to collect a large set of real-life data on medicines uses in older patients (≥65 years).

Development of an HPLC/UV method for the evaluation of extractables and leachables in plastic: Application to a plastic-packaged calcium gluconate glucoheptonate solution.

Calcium gluconate glucoheptonate (GGCa) is known to interact with glass containers, leading to the leaching of aluminum from the glass into the solution at toxic level. Therefore, plastic containers seem to be a preferable packaging alternative. Nevertheless, plastics contain potentially toxic additives which could be released into the solution.

Cyanine derivative as a suitable marker for thermosensitive in situ gelling delivery systems: In vitro and in vivo validation of a sustained buccal drug delivery.

Buccal administration route is a promising way for a large number of drugs exhibiting a low oral bioavailability. The present work describes the formulation and evaluation of a mucoadhesive and thermosensitive in situ gelling delivery system based on poloxamer 407, poloxamer 188 and xanthan gum for buccal drug delivery. First, the mucoadhesion properties were evaluated using a tensile test.