Therapeutic delivery最新文献

Aim: In this study, we developed a dual pH and time-dependent formulation for targeted colonic release, aiming at minimizing adverse effect and enhancing anticancer efficacy of colchicine in the treatment of colorectal cancer.

Materials and methods: To achieve this, colchicine was loaded in zein nanoparticles (Col-Z NP) which were further optimized and encapsulated in Eudragit S100 coated capsules. A full factorial design was employed to determine the optimal condition for preparation of Col-Z NP.

Results: The optimized Col-Z NPs exhibited a spherical shape with particle size of 104.3 ± 1.6 nm, polydispersity index of 0.27 ± 0.01, zeta potential of 29.0 ± 0.1 mV, encapsulation efficiency of 59.8 ± 4.8%, release efficiency over 8 h of 45.5 ± 2.7%, and drug loading of 13.0 ± 0.0%. No notable difference in cytotoxicity was observed between free colchicine and Col-Z NPs at comparable concentrations. The cellular uptake study showed more uptake for coumarin 6 loaded Z NPs compared to free coumarin 6. Colchicine release from coated capsules was restricted to around 3% in gastric medium and increased to about 8% in simulated intestine medium, respectively.

Conclusion: Results suggest that Eudragit S100 coated capsules containing Col-Z NP could be effective delivery system for colchicine to target colorectal tumors.

This month saw approvals for two products employing Halozyme's Enhanze drug delivery technology (BMS's Opdivo and Johnson and Johnson's DARZALEX FASPRO®). A number of collaborations between industry partners and charities to fight the disease, including Duchenne muscular dystrophy and Epidermolysis Bullosa, have been announced. Successful clinical trial data was disclosed for products employing a wide variety of therapeutic delivery technologies including Perfuse Therapeutics intravitreal implant for glaucoma, Aspen Neurosciences precision delivery of an autologous dopaminergic neuronal precursor cell therapy for Parkinson's disease and Resurge Therapeutics IntraProstatic Drug Elution (IPDE) therapy for prostate cancer.

Background: Drug delivery to perilymph after crossing the round window membrane is paramount important for inner ear disease management. Intratympanic (IT) injection of emulsion-like dispersions augments cinnarizine (CNZ) and morin hydrate (MH)-Lipoid E80 complex permeation into perilymph in a healthy rabbit inner ear model.

Methods: A Box-Behnken design (BBD) followed by artificial neural network (ANN)-linked Levenberg - Marquardt (LM) algorithm was used for optimizing the injection formula. Immediately after 30-120 minutes post-IT injections, the concentration levels of CNZ and MH in both perilymph and plasma were monitored.

Results: The ANN-linked LM algorithm displayed lower prediction and mean squared errors as well as higher correlation coefficient values for all responses when compared to the corresponding values shown by BBD. The IT injections possessed 156.8 ± 8.5 nm mean particle size, 42.70 ± 4.20 mV zeta potential, >98% CNZ and MH release within 10-20 minutes dissolution in pH 7.4 artificial perilymph solution, >97.26% cell viability in MTT assay and near normal histopathology. The 63.07 ± 23.62 µg/ml CNZ and 82.51 ± 8.33 µg/ml MH were attained in perilymph at 60 minutes post-IT injections.

Conclusion: The IT-injected formulation can be used to co-deliver two drugs in perilymph for managing inner ear diseases.

Lipid nanoparticles (LNPs) are multicomponent delivery vehicles for nucleic acids that are generally comprised of ionizable lipids, phospholipids, cholesterol and lipid-poly(ethylene glycol) molecules. It is well established that both the composition and relative amounts of each component significantly impact the efficiency of nucleic acid delivery by LNPs, as well as their organ-specific targeting. However, the post-delivery fate of every component is less discussed such as the degradation, clearance, and retention in the body. The longevity and metabolites of each component can greatly influence overall tolerability and safety. For instance, slowly degrading ionizable lipids, which comprise around 50% of the LNP, have been shown to illicit an extended inflammatory response. In this review significant importance is placed on chemistries that improve the tolerability and safety of certain LNP components, such as molecular modifications to ionizable lipids, lipid-poly(ethylene glycol) and nucleic acids. Additionally, we discuss how formulation strategies, such as the amount of cholesterol and phospholipids added to optimize clearance, can enhance biodegradability and reduce inflammation. Furthermore, this review will provide an understanding of the considerations around designing LNP components for better or more predictable metabolism such modified nucleic acids and biodegradable chemical linkers in ionizable lipids.

Objective: The presence of overexpressed folate-receptor and high concentration of glutathione (GSH) in liver cancer cells has been exploited and we have synthesized Folic acid-Dextran-Cystamine-Stearic acid (FDCS) for efficient and multifunctional delivery of the drug sorafenib (SAF) to enhance the anticancer effects.

Methods: The characteristics of micelles such as physicochemical properties and in vitro release were investigated. The pharmacokinetic characteristics of the micelle and SAF groups in rats were investigated. In vitro and in vivo anti-tumor experiments were performed with HepG2 cells.

Results: SAF-FDCS was successfully prepared and characterized. The cellular experiments showed that SAF-FDCS significantly enhanced the toxicity and inhibitory effects on HepG2 cells compared with free drug and the other micelles without smart response, and the uptake capacity of cellular HepG2 for SAF-FDCS was significantly higher than the groups without folic acid. Pharmacokinetic results showed that SAF-FDCS revealed a longer circulation time than free SAF. In addition, the tumor inhibition rate of SAF-FDCS in the subcutaneous graft tumor model of HepG2 cells was 84.6%, significantly higher than in other groups.

Conclusions: These results demonstrated the feasibility of SAF-FDCS micelles in inhibiting tumor growth and their superiority in anti-cancer effects compared to free drugs and normal micelles.

Aim: The present research aimed to develop a transdermal formulation of Curcuminoids utilizing eucalyptus oil as a permeation enhancer.

Material & method: Design-based optimization studies were performed to select the concentration of excipients and to prepare the nano emulsion. The eucalyptus oil was selected to develop the curcuminoids emulgel. The developed emulgel was evaluated for permeation using human skin and analyzed by HPLC. The emulgel was also evaluated for anti-inflammatory potential as compared to Curcuminoid gel formulation without permeation enhancer.

Results: Permeability studies performed using human skin with subsequent analysis of the samples by HPLC revealed that developed formulation was three times better as compared to formulation without permeation enhancer. The enhanced penetration attributed to polarity alteration, liquidation, and disruption of lipid bilayer by the terpenes present in essential oils. Literature also suggested that monoterpenes like 1,8 cineole could disrupt the lipid bilayer of skin and thus result in better penetration. The improved permeability could also be responsible for the enhanced anti-inflammatory potential (p < 0.01) of the developed nano-emulgel.

Conclusion: In nutshell, we can conclude that curcuminoids have the potential to be developed as emulgel with eucalyptus oil as a penetration enhancer.

Hyaluronic acid (HA) is a widely available, bio-compatible, polysaccharide with unique physical and chemical properties, which have inspired its application in many fields. Firstly, HA is a significant representative in wound healing, embryonic development, repair as well as regeneration. Secondly, HA exhibits pregnant meaning in cancer progression. Tumor cell proliferation, invasiveness, and motility can be modulated by the accumulation of HA in tumor stoma. Thirdly, HA is an actor in regulation processes during the angiogenesis. The level of HA, even low-molecular-weight HA, is considered to be a biomarker of tumor malignancy. Within this work, an intense overview of its application and the use of HA in drug delivery systems is given.HA plays a crucial role in many cases, such as cell signaling, morphogenesis, matrix organization, tissue regeneration, and pathobiology. Biocompatibility, mucoadhesivity, hygroscopicity, biodegradability, and viscoelasticity are to mention as physico-chemical properties of hyaluronan. This is why exogenous HA is investigated for drug delivery systems and exhibits a representative therapy of cancer, esthetic medicine, rhinology, arthrology, and cosmetics.In the end, the proof of concept presented by clinical trials is convincing to further investigate native HA as well as modified one for therapeutic delivery purposes.

Aim: The present study focused on the development of taste-masked medicated chewing gums loaded with Sertraline- cyclodextrin Inclusion Complex to enhance patient compliance and palatability.

Method: The inclusion complexes were prepared by kneading method and underwent evaluations utilizing analytical techniques and in-vitro taste evaluation using E-Tongue. The inclusion complex was then impregnated into medicated chewing gums using directly compressible gum-based Health in Gum® employing Central Composite Design. The gums were assessed for weight variation, drug content (%), hardness, in-vitro-dissolution studies etc. Next, ex-vivo buccal permeation, stability testing, and Texture Profile Analysis were conducted on the optimized chewing gum batch.

Results: The results of E-Tongue showed the credibility of the cyclodextrin in taste masking of bitter actives. The optimized formulation of chewing gum demonstrated 4.1 ± 0.88 kg/cm² of hardness and 80.6 ± 0.65% drug release. Ex-vivo investigations showed a significant amount of drug permeation. The amount of plasticizer and gum base used impacted the hardness and release of the drug in - vitro as demonstrated by Design of Experiments.

Conclusion: The outcomes showed that taste-masked medicated chewing gum would be a superior choice to traditional tablet formulation with improved drug release, and palatability.