1,721,106 research outputs found
Chitosan in nasal delivery systems for therapeutic drugs
No full textThere is an obvious need for efficient and safe nasal absorption enhancers for the development of therapeutically efficacious nasal products for small hydrophilic drugs, peptides, proteins, nucleic acids and polysaccharides, which do not easily cross mucosal membranes, including the nasal. Recent years have seen the development of a range of nasal absorption enhancer systems such as CriticalSorb® (based on Solutol HS15) (Critical Pharmaceuticals Ltd), Chisys® based on chitosan (Archimedes Pharma Ltd) and Intravail® based on alkylsaccharides (Aegis Therapeutics Inc.), that is presently being tested in clinical trials for a range of drugs. So far, none of these absorption enhancers have been used in a marketed nasal product. The present review discusses the evaluation of chitosan and chitosan derivatives as nasal absorption enhancers, for a range of drugs and in a range of formulations such as solutions, gels and nanoparticles and finds that chitosan and its derivatives are able to efficiently improve the nasal bioavailability. The revirtew also questions whether chitosan nanoparticles for systemic drug delivery provide any real improvement over simpler chitosan formulations. Furthermore, the review also evaluates the use of chitosan formulations for the improvement of transport of drugs directly from the nasal cavity to the brain, based on its mucoadhesive characteristics and its ability to open tight junctions in the olfactory and respiratory epithelia. It is found that the use of chitosan nanoparticles greatly increases the transport of drugs from nose to brain over and above the effect of simpler chitosan formulations
Nasal vaccination against SARS-CoV-2: Synergistic or alternative to intramuscular vaccines?
Full text linkIt is striking that all marketed SARS-CoV-2 vaccines are developed for intramuscular administration designed to produce humoral and cell mediated immune responses, preventing viremia and the COVID-19 syndrome. They have a high degree of efficacy in humans (70-95%) depending on the type of vaccine. However, little protection is provided against viral replication and shedding in the upper airways due to the lack of a local sIgA immune response, indicating a risk of transmission of virus from vaccinated individuals. A range of novel nasal COVID-19 vaccines are in development and preclinical results in non-human primates have shown a promising prevention of replication and shedding of virus due to the induction of mucosal immune response (sIgA) in upper and lower respiratory tracts as well as robust systemic and humoral immune responses. Whether these results will translate to humans remains to be clarified. An IM prime followed by an IN booster vaccination would likely result in a better well-rounded immune response, including prevention (or strong reduction) in viral replication in the upper and lower respiratory tracts
3D printed clotrimazole intravaginal ring for the treatment of recurrent vaginal candidiasis
Full text linkVulvovaginal candidiasis is a vaginal infection caused by the fungal pathogen Candida albicans that, most commonly, affects women of reproductive age. Its first-line treatment consists in topical applications of conventional drug formulations (e.g., creams, gels, tablets) containing imidazole drugs. The treatment involves single or multiple daily applications and, in the case of recurrences, daily administration of oral antifungal drugs for up to one month. Intravaginal rings are flexible, biocompatible medical devices that, compared to conventional drug formulations, offer the possibility of a controlled vaginal drug delivery over a determined period with a single application, thus increasing patient compliance. Among innovative manufacturing techniques, in recent years, fused deposition modeling 3D printing has emerged in the pharmaceutical field to produce different therapeutics combining drugs and polymers. This technique allows to print objects layer by layer with many different thermoplastic materials after a computer-assisted design. Thermoplastic polyurethanes are flexible and biocompatible materials that can be efficiently employed for the manufacturing of drug release systems, already utilized to prepare vaginal devices. In this work, we produced a clotrimazole-loaded intravaginal ring by fused deposition modeling 3D printing combining the drug with thermoplastic polyurethane using hot melt extrusion. The rings were computer-designed and then printed with two different drug concentrations (i.e., 2% and 10% w/w). The intravaginal rings were first tested in an agar-diffusion test to evaluate their effectiveness against C. albicans; and the 10% loaded ring was selected for further studies. Drug release was evaluated in two different media (i.e., 50% ethanol and vaginal fluid simulant) showing a sustained release over a period of seven days. Next, in vitro time-kill analysis against C. albicans in simulated vaginal fluid was performed and displayed a complete growth inhibition after 5 days, compared to the control. These results suggest a potential application of these 3D printed intravaginal rings for the treatment of vulvovaginal candidiasis and for the long-time treatment of recurrences
An easy 3D printing approach to manufacture vertical diffusion cells for in vitro release and permeation studies
Full text linkVertical diffusion cells are commonly used in the pharmaceutical and cosmetic fields to study the release and permeation of active ingredients through synthetic or biological membranes. Nevertheless, the commercially available glass-based systems are expensive and need to be carefully handled due to their fragility. Fused deposition modeling 3D printing is an additive manufacturing technique that allows producing objects layer by layer using different thermoplastic materials. Among them, polypropylene is a robust, flexible, and chemically inert polymer that can resist to many organic solvents. In this work, we designed and printed a vertical diffusion cell following pharmacopeia requirements by using polypropylene in a fused deposition modeling 3D printer. To keep the system thermostated, the developed model fits in a heating block to avoid the use of water recirculating system. The vertical diffusion cells were leak-free and presented chemical resistance and no interaction with model molecules (i.e., caffeine, diclofenac sodium, and glycyrrhetinic acid). The 3D printed cells were compared to commercially available glass cells and then two different types of synthetic membranes (i.e., PDMS and Strat-M®) were used to evaluate the permeation of a caffeine hydrogel. The developed 3D printed testing system could represent an efficient alternative to the glass-based equipment
Microfluidic production of protein loaded chimeric stealth liposomes
No full textThe addition of polyethylene glycol (PEG) on the surface of liposomes increases their circulation time when administered intravenously. However, the inclusion of PEG using PEGylated phospholipids could result in a possible micelles formation. The development of chimeric systems mixing synthetic biocompatible and biodegradable PEG-containing copolymers with lipids is a strategy to obtain as well PEGylated liposomes. Microfluidics is an innovative manufacturing technology easy to scale up that presents high reproducibility, low batch-to-batch variation, and better control over particles characteristics. Taking advantage of this technique, in this research work, chimeric stealth liposomes were produced mixing five different synthesized methoxy-poly(ethylene glycol)-block-poly(δ-decalactone) (mPEG-PDL, varying in polymer length) with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and cholesterol. The obtained chimeric formulations were around 150 nm in size with a narrow distribution and an almost neutral surface charge. Ovalbumin (OVA) was used as a model protein to evaluate the loading potential reaching an encapsulation efficiency of 41±4 %. The prepared systems showed no cytotoxicity in vitro on THP-1 cell with an uptake up to 89±4 % after 3 h. Finally, protein integrity after encapsulation was confirmed with DQ-OVA. In this work, we demonstrated that using microfluidics, it is possible to produce stable and highly protein-loaded chimeric stealth liposomes with good physicochemical characteristics, no toxicity, protein integrity, and effective uptake by endocytosis
Chitosans as new tools against biofilms formation on the surface of silicone urinary catheters
No full textUrinary catheters contamination by microorganisms is a major cause of hospital acquired infections and represents a limitation for long-term use. In this work, biofilms of Klebsiella pneumoniae and Escherichia coli clinical isolates were developed on urinary catheters for 48 and 72 h in artificial urine medium (AUM) with different molecular weight chitosans (AUM-CS solutions) at pH 5.0. The number of viable bacteria was determined by standard plate count agar while crystal violet (CV) staining was carried out to assess biomass production (optical density at 570 nm) in the mentioned conditions. Re-growth of each strain was also evaluated after 24 h re-incubation of the treated catheters. Significant decreases of log CFU/catheter and biomass production were observed for all the biofilms developed in AUM-CS compared with the controls in AUM. The percentages of biofilm removal were slightly higher for E. coli biofilms (up to 90.4%) than those of K. pneumoniae (89.7%); in most cases, the complete inhibition of bacterial re-growth on treated catheter pieces was observed. Contact time influenced chitosan efficacy rather than its molecular weight or the biofilms age. The results confirmed the potentiality of chitosans as a biomacromolecule tool to contrast biofilm formation and reduce bacterial re-growth on urinary catheters
Development and evaluation of a 3D printing protocol to produce zolpidem-containing printlets, as compounding preparation, by the pressurized-assisted microsyringes technique
Full text linkInsomnia is a chronic disorder with a mean prevalence ranged from 6% to 15% worldwide. The usual pharmacologic treatment for insomnia has been benzodiazepines and barbiturates. More recently, z-drugs were introduced in the therapeutic arsenal to maximize benefits and minimize treatment damage. Zolpidem tartrate, whose primary indication is for sleep initiation problems, is conventionally used at a recommended dose of 5 mg for women as well as elderly patients (< 65 years-old) and 10 mg for non-elderly men. However, it was demonstrated that the dose of zolpidem should be adjusted according to the gender, age, condition of the patient and the presence of polypharmacy to decrease the occurrence of adverse events. Faced with the therapeutic limitations inherent to marketed products, magistral preparations offer medical and legal alternatives to mass treatment. The use of a semi-automatic technique, with standardized protocol, such as 3D printing should be advantageously implemented as an alternative to standard compounding procedures. In this work, the pressure-assisted microsyringes method was selected as it allows the tridimensional printing, and so the customization of the dose, by easily extruding a viscous semi-liquid material, called "slurry", through a syringe at room temperature. It has been demonstrated that this methodology allows obtaining printlets that responded to the zolpidem-containing tablets monograph of the US pharmacopoeia Edition 42. The compounding preparations proposed in this work therefore have the same criteria of requirements as a commercial form
Characterization of the interaction between chitosan and inorganic sodium phosphates by means of rheological and optical microscopy studies
No full textThe physicochemical and rheological properties of chitosan and two different inorganic sodium phosphate dispersions (NaH2PO4 and Na3PO4) were investigated in order to elucidate the role of different factors, such as ratios between polymer and sodium inorganic phosphates, different pHs and storage stability, on the gelling properties of chitosan. This was deemed opportune since physico-chemical characterizations of chitosan in the literature often appear incomplete and questionable. We also compared the elastic modulus values of the different chitosan/inorganic phosphate systems and examined their behaviour through optical microscopy analyses. The most efficient formulations that showed a thermogelling capacity with a significant gel transition behaviour after 24 h were the NaH2PO4/chitosan and Na3PO4/chitosan systems at ratio 2 and pH 7.0. These results confirmed the importance of the pH value and ratio selection for the final systems
Dextran and its potential use as tablet excipient
Full text linkDextrans are a class of carbohydrate polymers extensively applied in pharmaceutical applications, particularly as drug conjugate macromolecular carriers or drug delivery systems. These polysaccharides improve the stability of the therapeutics enabling also the control of their release, via either the parenteral and or oral routes. In the latter case, due to their gel forming ability they may have potential as hydrophilic matrix tablets for sustained drug release.
In this paper, we investigated the behaviour of different molecular weight (1, 40, 500 and 2300 kDa) dextrans as tabletting excipients. Powder particle size and hygroscopic studies have been reported, together with tabletability, tablet stability and tablet swelling. Moreover we use tramadol as model compound to evaluate the ability of dextrans to control drug dissolution. The results suggest that dextrans with lower molecular weights may be a promising excipient to be used as filler for immediate release tablets, due to their good tabletability and fast dissolution rate, while dextrans with higher molecular weights could be an efficient disintegrant due to their swelling ability
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