Therapeutic delivery最新文献

Background: Olmesartan medoxomil, classified as BCS class II due to its poor water solubility, exhibits a low oral bioavailability of 28.6%.

Materials and methods: Microballoons of Olmesartan medoxomil were formulated using the ionotropic gelation technique and subjected to various evaluation parameters.

Results: The particles were found to be in the range of 85.11 to 312.6 µm. The prepared microballoons remained buSSoyant for more than 12 hours and showed percentage of cumulative drug release between 56.32-83.62%. In vivo studies showed significant reduction in Systolic blood pressure (SBP) in optimized formulation (OF).

Conclusion: The formulated microballoons (hollow microspheres) emerged as a promising option for an oral gastro retentive controlled drug delivery system for Olmesartan medoxomil.

The ongoing global health crisis caused by multidrug-resistant (MDR) bacteria necessitates quick interventions to introduce new management strategies for MDR-associated infections and antimicrobial agents' resistance. Phage therapy emerges as an antibiotic substitute for its high specificity, efficacy, and safety profiles in treating MDR-associated infections. Various in vitro and in vivo studies denoted their eminent bactericidal and anti-biofilm potential. This review addresses the latest developments in phage therapy regarding their attack strategies, formulations, and administration routes. It additionally discusses and elaborates on the status of phage therapy undergoing clinical trials, and the challenges encountered in their usage, and explores prospects in phage therapy research and application.

Background: The integration of immunotherapy alongside chemotherapy represents a crucial approach in the treatment of cancer. Herein we report the SN-38-indoximod conjugate nano-prodrug to address the difficulties encountered by individuals. In this prodrug, SN-38 is connected to indoximod through a specific disulfide linker, which enables the release of the components in response to the tumor microenvironment characterized by elevated levels of glutathione, thereby facilitating programmed chemoimmunotherapy.

Results: SN-38-indoximod conjugate was synthesized and fabricated to nano-prodrug by reprecipitation method. It showed comparable anti-cancer activity against A549 cells than SN-38 (IC₅₀ = 0.24 ± 0.01 µM) with IC₅₀ value 0.32 ± 0.04 µM. It inhibited 90% A549 cell at very lower concentration (IC₉₀ = 6.07 ± 0.41 µM) as compared with SN-38 (IC₉₀ = 24.60 ± 1.24 µM) and mixture of SN-38: indoximod (1:1, IC₉₀ >30 µM). The nano-prodrug showed better size distribution profile and dispersion stability contains nanoparticles in effective size range (80-160 nm) required for the EPR effect.

Conclusion: This research offers valuable insights into the advancement of conjugate nano-prodrugs exhibiting synergistic pharmacological effects, while also presenting novel opportunities for the design of prodrug molecules capable of releasing drugs in response to diverse triggers.

Aims: A new self-nanoemulsifying drug delivery system (SNEDDS) was developed for erlotinib (Ert) oral delivery.

Materials and methods: A pseudo-ternary phase diagram for olive oil, Tween 80 and polyethylene glycol (PEG) 600 mixtures, was firstly constructed. Based on the data about Ert solubility and cytotoxicity of these components, a SNEDDS composed of 10% olive oil, 20% Tween 80 and 70% (V/V) polyethylene glycol 600 was selected for Ert loading (Ert-SNEDDS).

Results and conclusions: SNEDDS formed 31.2-nm droplets upon dilution in water, and Ert loading led to increment in the oil droplets to 83.9 ± 0.6 nm. Ert-SNEDDS represented a loading capacity and an entrapment efficiency of 22.7 ± 0.7 and 40.7 ± 0.5%, respectively. Ert release from Ert-SNEDDS was monitored in both a mixture of phosphate buffer saline and 0.5% Tween 80, and artificial gastric fluid. Ert-SNEDDS was orally administrated in rats, and the Ert plasma level was monitored over time to measure pharmacokinetic parameters. Ert-SNEDDS led to enhancement in the drug bioavailability and changed the release route of Ert. Ert-SNEDDS showed enhanced cytotoxicity toward ASPC-1 and PANC-1 cells, and half-maximal inhibitory concentration values were obtained and compared with free Ert. Ert-SNEDDS may be considered as an alternative route for oral Ert delivery.

Aim: The study aimed to formulate solid lipid nanoparticles (SLNs) for the transdermal delivery of PPL to improve skin retention and efficacy.

Materials and method: The particle size distribution of SLNs was determined and the morphology of SLNs was also analyzed by SEM. In-vitro, ex-vivo and in vivo evaluations were done for PPL loaded SLN. The safety of drug delivery systems was assayed using MTT test.

Results: The results indicated successful encapsulation of PPL in SLNs (59.38%), which exhibited a spherical shape and smooth surface. Compared to PPL solution, SLNs demonstrated a prolonged drug release profile in vitro. Stability tests over three months showed no significant changes in entrapment efficiency or size distribution. Enhanced permeation through shed snake and rat skin was observed with SLNs compared to the PPL solution. Ex-vivo and in vivo studies confirmed that PPL-loaded SLNs significantly increased drug content in the skin. Importantly, the SLNs displayed biocompatibility, as no significant cytotoxic effects were noted, and they were nonirritating to rat skin.

Conclusion: To the best of our knowledge, this is the first study that indicates SLNs can be considered as a promising nanocarriers for transdermal delivery of PPL.

Androgenic alopecia has a high incidence, affecting 80% of men and 50% of women in their lifetimes. Although not a life-threatening disease, it can be a deep psychological burden to patients and still lacks an effective and safe treatment. Dutasteride is a5-alpha-reductase inhibitor approved to treat benign prostatic hyperplasia that is also commonly prescribed off-label to treat androgenic alopecia. However, oral dutasteride may cause several severe sexual and neurological sideeffects. Therefore, an effective, localized dutasteride treatment that can reduce the effects of systemic uptake is of great interest. Here, we review available therapies to treat androgenic alopecia focusing on topicalformulations developed thus far-including minoxidil, finasteride, and cosmetics-and on dutasteride-loaded nanocarriers targeting hair follicles.

Aim: Abemaciclib (ABE) is an anticancer drug that suffers from low bioavailability and multidrug resistance. This study aims to develop ABE-loaded solid lipid nanoparticles (ABE-SLNs), which will enhance drug solubility and lead to increased cellular uptake and enhanced cytotoxicity when delivering tumor cells.

Methods: Melt emulsification followed by ultrasonication was used as a method of preparation and Quality-by-Design (QbD) was utilized to optimize ABE-SLNs.

Results: The optimized ABE-SLNs consist of Precirol-ATO5 as a lipid and Brij-58 as a surfactant. The particle size, PDI value, and zeta potential of the optimized formulation were 170.4 ± 0.49 nm, 0.25 ± 0.014, and -26.4 ± 0.1 mV, respectively. It also showed sustained release behavior and a high entrapment efficiency of 79.96%. ABE-SLNs exhibited enhanced anticancer activity in the MDA-MB-231 and T47D breast cancer cell lines compared to pure ABE. In Caco-2 human colonic cell lines, ABE-SLNs also showed increased cellular uptake.

Conclusion: The use of QbD to achieve high entrapment efficiency and sustained release in ABE-SLNs, coupled with enhanced cellular uptake and cytotoxicity, represents a novel approach that could set a new standard for nanoparticle-based drug delivery systems.

This Industry Update covers the period from 1^st October through to 31 October 2024 and is based on information sourced from company press releases, scientific literature, patents, and various news websites. This month saw two biotech company acquisitions being made by larger biopharma companies with Modifi Biosciences, a company focussing on the development of novel small molecule anticancer therapeutics, being acquired Merck, and AbbVie acquiring Aliada Therapeutics, which focuses on the treatment of central nervous system disorders. Elektrofi and Archon Biosciences both announced new investments, respectively, to support the development of novel high concentration subcutaneous drug delivery technology and for the development Antibody cages for therapeutic applications. GSK and Cambridge University announced a new five-year collaboration focusing on kidney and respiratory disease, and Aeropump and Resyca announced the launch of a new soft mist nasal delivery system that they have been jointly developing. UCB gained FDA approval for a higher dose of its injectable drug, BIMZELX for the treatment of autoimmune disorders, and AbbVie FDA approval for a continuous infusion treatment for Parkinson's Disease. Eisai announced it has completed its submission to the FDA for a subcutaneous version of its already approved therapy for Alzheimer's Disease. Clinical research updates included Johnson and Johnson announcing termination of a Phase III trial evaluating an implanted combination device for the treatment of bladder cancer, and Lilly announced positive results for modified dosing regimen for its approved Alzheimer's drug, Kisunla (donanemab).In October, the PDA held its annual Universe of Prefilled Syringes conference at which several updates on developments in injectable drug delivery were made. Scientific updates relating to therapeutic delivery included: a controlled drug delivery technology that enables a complete course of antibiotics to be delivered; a new lipid-based delivery system that improves the safety and efficacy of gene therapies; and the use of tiny controllable robots to enable targeted drug delivery of multiple therapeutics.

Cancer is increasingly being recognized as a global health issue with considerable unmet medical need. Despite the rapid progression of anticancer pharmaceuticals, there are still significant challenges for the effective management of cancer. In many circumstances, cancer cells are difficult to detect and treat. Combination of nanovesicles (NVs) and magnetic nanoparticles (MNPs), referred as magnetic nanovesicles (MNVs), is now well recognized as a potential theranostic option for improving cancer treatment outcomes and reducing adverse effects. MNVs can be used for monitoring the long-term fate and functional benefits of cancer therapy. Moreover, MNV-mediated hyperthermia mechanism has been explored as a potential technique for triggering cancer cell death, and/or controlled release of laden cargo. In this review, we focus on the unique characteristics of MNVs as a promising avenue for targeted drug delivery, diagnosis, and treatments of cancer or tumor. Moreover, we discuss critical considerations related to the issues raised in this area, which will guide future research toward better anti-cancer therapeutics for clinical applications.

Cannabidiol (CBD), extracted from Cannabis sativa L., holds therapeutic promise without inducing psychoactive effects seen with Δ9-tetrahydrocannabinol. Its interaction with the endocannabinoid system plays a pivotal role in regulating mood, pain perception and immune function. Nevertheless, CBD encounters hurdles in clinical application due to its poor bioavailability and water solubility. To overcome these limitations, researchers are exploring microencapsulation techniques, which involve encapsulating CBD within protective matrices. This comprehensive review offers insights into various microencapsulation methods for CBD, scrutinizing their advantages, limitations and implications for formulation optimization. By elucidating the potential of microencapsulation, this review underscores its promise in refining CBD therapy and addressing challenges associated with administration.