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Pharmaceutics Jun 2024Etomidate is a general anesthetic that has shown good hemodynamic stability without significant cardiovascular or respiratory depression. Despite several kinds of dosage...
Etomidate is a general anesthetic that has shown good hemodynamic stability without significant cardiovascular or respiratory depression. Despite several kinds of dosage forms having been reported for this drug, formulation types are very limited in clinical practice, and brain-targeted formulations for this central nervous system (CNS) drug have been rarely reported. Moreover, studies on the biocompatibility, toxicity, and anesthetic effects of the etomidate preparations in vivo were inadequate. The present study was to develop lactoferrin-modified liposomal etomidate (Eto-lip-LF) for enhanced drug distribution in the brain and improved anesthetic effects. Eto-lip-LF had good stability for storage and hemocompatibility for intravenous injection. Compared with the non-lactoferrin-containing liposomes, the lactoferrin-modified liposomes had notably enhanced brain-targeting ability in vivo, which was probably realized by the binding of transferrin with the transferrin and lactoferrin receptors highly distributed in the brain. Eto-lip-LF had a therapeutic index of about 25.3, higher than that of many other general anesthetics. Moreover, compared with the commercial etomidate emulsion, Eto-lip-LF could better achieve rapid onset of general anesthesia and rapid recovery from anesthesia, probably due to the enhanced drug delivery to the brain. The above results demonstrated the potential of this lactoferrin-modified liposomal etomidate to become an alternative preparation for clinical general anesthesia.
PubMed: 38931926
DOI: 10.3390/pharmaceutics16060805 -
Pharmaceutics Jun 2024In the past several decades, polymeric microparticles (MPs) have emerged as viable solutions to address the limitations of standard pharmaceuticals and their...
In the past several decades, polymeric microparticles (MPs) have emerged as viable solutions to address the limitations of standard pharmaceuticals and their corresponding delivery methods. While there are many preclinical studies that utilize polymeric MPs as a delivery vehicle, there are limited FDA-approved products. One potential barrier to the clinical translation of these technologies is a lack of understanding with regard to the manufacturing process, hindering batch scale-up. To address this knowledge gap, we sought to first identify critical processing parameters in the manufacturing process of blank (no therapeutic drug) and protein-loaded double-emulsion poly(lactic-co-glycolic) acid MPs through a quality by design approach. We then utilized the design of experiments as a tool to systematically investigate the impact of these parameters on critical quality attributes (e.g., size, surface morphology, release kinetics, inner occlusion size, etc.) of blank and protein-loaded MPs. Our results elucidate that some of the most significant CPPs impacting many CQAs of double-emulsion MPs are those within the primary or single-emulsion process (e.g., inner aqueous phase volume, solvent volume, etc.) and their interactions. Furthermore, our results indicate that microparticle internal structure (e.g., inner occlusion size, interconnectivity, etc.) can heavily influence protein release kinetics from double-emulsion MPs, suggesting it is a crucial CQA to understand. Altogether, this study identifies several important considerations in the manufacturing and characterization of double-emulsion MPs, potentially enhancing their translation.
PubMed: 38931917
DOI: 10.3390/pharmaceutics16060796 -
Pharmaceutics Jun 2024A classical emulsion formulation based on petrolatum and mineral oil as the internal phase with emulsifier wax as a typical topical emulsion cream was investigated for...
A classical emulsion formulation based on petrolatum and mineral oil as the internal phase with emulsifier wax as a typical topical emulsion cream was investigated for the effect of process parameters on drug product quality and performance attributes. The Initial Design of Experiment (DoE) suggested that an oil phase above 15%, coupled with less than 10% emulsifying wax, resulted in less stable emulsions. Different processing parameters such as homogenization speed, duration, cooling rate, and final temperature showed minimal influence on properties and failed to improve stability. The final DoE suggested that the optimal emulsion stability was achieved by introducing a holding period midway through the cooling stage after solvent addition. Within the studied holding temperature range (25-35 °C), a higher holding temperature correlated with increased emulsion stability. However, the application of shear during the holding period, using a paddle mixer, adversely affected stability by disrupting the emulsion microstructure. IVRT studies revealed that the release of lidocaine was higher in the most stable emulsion produced at a holding temperature of 35 °C compared to the least stable emulsion produced at a holding temperature of 25 °C. This suggests that a holding temperature of 35 °C improves both the stability and active release performance. It appears that a slightly higher holding temperature, 35 °C, allows a more flexible and stable emulsifying agent film around the droplets facilitating stabilization of the emulsion. This study offers valuable insights into the relationship between process parameters at various stages of manufacture, microstructure, and various quality attributes of emulsion cream systems. The knowledge gained will facilitate improved design and optimization of robust manufacturing processes, ensuring the production of the formulations with the desired critical quality attributes.
PubMed: 38931894
DOI: 10.3390/pharmaceutics16060773 -
Pharmaceutics May 2024This review explores the intersection of microfluidic technology and complex emulsion development as a promising solution to the challenges of formulations in multi-drug... (Review)
Review
This review explores the intersection of microfluidic technology and complex emulsion development as a promising solution to the challenges of formulations in multi-drug therapy (MDT) and polypharmacy. The convergence of microfluidic technology and complex emulsion fabrication could herald a transformative era in multi-drug delivery systems, directly confronting the prevalent challenges of polypharmacy. Microfluidics, with its unparalleled precision in droplet formation, empowers the encapsulation of multiple drugs within singular emulsion particles. The ability to engineer emulsions with tailored properties-such as size, composition, and release kinetics-enables the creation of highly efficient drug delivery vehicles. Thus, this innovative approach not only simplifies medication regimens by significantly reducing the number of necessary doses but also minimizes the pill burden and associated treatment termination-issues associated with polypharmacy. It is important to bring forth the opportunities and challenges of this synergy between microfluidic-driven complex emulsions and multi-drug therapy poses. Together, they not only offer a sophisticated method for addressing the intricacies of delivering multiple drugs but also align with broader healthcare objectives of enhancing treatment outcomes, patient safety, and quality of life, underscoring the importance of dosage form innovations in tackling the multifaceted challenges of modern pharmacotherapy.
PubMed: 38931830
DOI: 10.3390/pharmaceutics16060707 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Tuberculosis (TB) is an airborne bacterial infection caused by (), resulting in approximately 1.3 million deaths in 2022 worldwide. Oral therapy with anti-TB drugs...
Tuberculosis (TB) is an airborne bacterial infection caused by (), resulting in approximately 1.3 million deaths in 2022 worldwide. Oral therapy with anti-TB drugs often fails to achieve therapeutic concentrations at the primary infection site (lungs). In this study, we developed a dry powder inhalable formulation (DPI) of clofazimine (CFZ) to provide localized drug delivery and minimize systemic adverse effects. Poly (lactic acid-co-glycolic acid) (PLGA) microparticles (MPs) containing CFZ were developed through a single emulsion solvent evaporation technique. Clofazimine microparticles (CFZ MPs) displayed entrapment efficiency and drug loading of 66.40 ± 2.22 %w/w and 33.06 ± 1.45 µg/mg, respectively. To facilitate pulmonary administration, MPs suspension was spray-dried to yield a dry powder formulation (CFZ SD MPs). Spray drying had no influence on particle size (~1 µm), zeta potential (-31.42 mV), and entrapment efficiency. Solid state analysis (PXRD and DSC) of CFZ SD MPs studies demonstrated encapsulation of the drug in the polymer. The drug release studies showed a sustained drug release. The optimized formulation exhibited excellent aerosolization properties, suggesting effective deposition in the deeper lung region. The in vitro antibacterial studies against H37Ra revealed improved (eight-fold) efficacy of spray-dried formulation in comparison to free drug. Hence, clofazimine dry powder formulation presents immense potential for the treatment of tuberculosis with localized pulmonary delivery and improved patient compliance.
PubMed: 38931422
DOI: 10.3390/ph17060754 -
Biomedicines May 2024Natural origin products are regarded as promising for the development of new therapeutic therapies with improved effectiveness, biocompatibility, reduced side effects,... (Review)
Review
Natural origin products are regarded as promising for the development of new therapeutic therapies with improved effectiveness, biocompatibility, reduced side effects, and low cost of production. Betulin (BE) is very promising due to its wide range of pharmacological activities, including its anticancer, antioxidant, and antimicrobial properties. However, despite advancements in the use of triterpenes for clinical purposes, there are still some obstacles that hinder their full potential, such as their hydrophobicity, low solubility, and poor bioavailability. To address these concerns, new BE derivatives have been synthesized. Moreover, drug delivery systems have emerged as a promising solution to overcome the barriers faced in the clinical application of natural products. The aim of this manuscript is to summarize the recent achievements in the field of delivery systems of BE and its derivatives. This review also presents the BE derivatives mostly considered for medical applications. The electronic databases of scientific publications were searched for the most interesting achievements in the last ten years. Thus far, it is mostly nanoparticles (NPs) that have been considered for the delivery of betulin and its derivatives, including organic NPs (e.g., micelles, conjugates, liposomes, cyclodextrins, protein NPs), inorganic NPs (carbon nanotubes, gold NPs, silver), and complex/hybrid and miscellaneous nanoparticulate systems. However, there are also examples of microparticles, gel-based systems, suspensions, emulsions, and scaffolds, which seem promising for the delivery of BE and its derivatives.
PubMed: 38927375
DOI: 10.3390/biomedicines12061168 -
BMJ Case Reports Jun 2024Flecainide is a medication used to treat supraventricular and ventricular tachyarrhythmias. Cases of overdoses are rare, however, can lead to significant cardiac...
Flecainide is a medication used to treat supraventricular and ventricular tachyarrhythmias. Cases of overdoses are rare, however, can lead to significant cardiac effects. In previous cases of flecainide toxicity, treatment with sodium bicarbonate, intravenous lipid emulsion and amiodarone have been reported to be effective in preventing cardiovascular collapse and reestablishing baseline rhythm. Here, we present a case of a man in his 40s presented with flecainide overdose with wide-complex tachycardia that was treated with intravenous sodium bicarbonate following failure of amiodarone to normalise QRS interval.
Topics: Humans; Flecainide; Male; Sodium Bicarbonate; Drug Overdose; Anti-Arrhythmia Agents; Electrocardiography; Adult; Infusions, Intravenous; Tachycardia; Amiodarone
PubMed: 38926125
DOI: 10.1136/bcr-2023-256391 -
International Journal of Pharmaceutics Jun 2024Breast cancer treatment can be challenging, but a targeted drug delivery system (DDS) has the potential to make it more effective and reduce side effects. This study...
Breast cancer treatment can be challenging, but a targeted drug delivery system (DDS) has the potential to make it more effective and reduce side effects. This study presents a novel nanotherapeutic targeted DDS developed through the self-assembly of an amphiphilic di-block copolymer to deliver the chemotherapy drug SN38 specifically to breast cancer cells. The vehicle was constructed from the PHPMA-b-PEAMA diblock copolymer synthesized via RAFT polymerization. A single emulsion method was then used to encapsulate SN38 within nanoparticles (NPs) formed from the PHPMA-b-PEAMA copolymer. The AS1411 DNA aptamer was covalently bonded to the surface of the micellar NPs, producing a targeted DDS. Molecular dynamics (MD) simulation studies were also performed on the di block polymeric system, demonstrating that SN38 interacted well with the di block. The in vitro results demonstrated that AS1411- decorated SN38-loaded HPMA NPs were highly toxic to breast cancer cells while having a minimal effect on non-cancerous cells. Remarkably, in vivo studies elucidated the ability of the targeted DDS to enhance the antitumor effect of SN38, suppressing tumor growth and improving survival rates compared to free SN38.
PubMed: 38925238
DOI: 10.1016/j.ijpharm.2024.124387 -
Journal de Mycologie Medicale Jun 2024Dermatophytosis is a critical sort of skin infection caused by dermatophytes. The long-term treatment of such skin infections may be improved through the application of...
Dermatophytosis is a critical sort of skin infection caused by dermatophytes. The long-term treatment of such skin infections may be improved through the application of nanotechnology. This study aimed to prepare griseofulvin zinc Nanohybrid emulsion (GF-Zn-NHE) to improve griseofulvin activity against dermatophytes and some opportunistic pathogenic yeasts and bacteria. The GF-Zn-NHE is prepared by ultra-homogenization ultra-sonication strategies and validated by UV-visible spectroscopy analysis that confirms presences of griseofulvin and Zn-NPs peaks at 265 and 360 nm, respectively. The GF-Zn-NHE has mean distribution size 50 nm and zeta potential in the range from -40 to -36 mV with no significant changes in size distribution and particle size within 120 day ageing. Fourier transform infrared spectroscopy spectrum confirmed the presence of griseofulvin and Zn-NPs stretching vibration peaks. Gamma ray has a negative influence on GF-Zn-NE production and stability. GF-Zn-NHE drug release 95% up to 24 h and 98% up to 72 h of GF was observed and Zinc 90% up to 24 h and 95% up to 72 h, respectively. High antimicrobial activity was observed with GF-Zn-NHE against dermatophytic pathogens in compare with GF, GF-NE, zinc nitrate and ketoconazole with inhibition zone ranged from 14 to 36 mm. The results have shown that the MIC value for Cryptococcus neoformans, Prophyromonas gingivalis and Pseudomonas aeruginosa is 0.125 mg ml and for Trichophyton rubrum, L. bulgaricus and Escherichia coli value is 0.25 mg ml and for Candida albicans, Malassezia furfur and Enterococcus faecalis is 0.5 mg ml and finally 1 mg ml for Streptococcus mutans. TEM of treated Cryptococcus neoformans cells with GF-Zn-NHE displayed essentially modified morphology, degradation, damage of organelles, vacuoles and other structures.
PubMed: 38925022
DOI: 10.1016/j.mycmed.2024.101489 -
Toxics May 2024From 2019 to 2020, antihistamines were found in 15% of all US drug overdose deaths, often co-administered with fentanyl, with 3.6% of overdose deaths due to... (Review)
Review
From 2019 to 2020, antihistamines were found in 15% of all US drug overdose deaths, often co-administered with fentanyl, with 3.6% of overdose deaths due to antihistamines alone. The most common antihistamine found in all these reported deaths is diphenhydramine, a ubiquitous, over-the-counter and clinically important medication. Currently, there is no antidote for diphenhydramine overdose. This review summarizes the adverse health effects and current emergency medicine treatments for diphenhydramine. Several emergency medicine case reports are reviewed, and the efficacy and outcomes of a variety of treatments are compared. The treatments reviewed include the more traditional antihistamine overdose therapeutics physostigmine and sodium bicarbonate, as well as newer ones such as donepezil, dexmedetomidine, and lipid emulsion therapy. We conclude that more study is needed to determine the ideal therapeutic approach to treating antihistamine overdoses.
PubMed: 38922056
DOI: 10.3390/toxics12060376