Current drug delivery最新文献

Background: Multidrug-resistant Mycobacterium tuberculosis (MDR-TB) is a major cause of death amongst tuberculosis patients. Nanomedicine avoids some limitations of conventional drug treatment and increases therapeutic efficacy against bacterial infections. However, the effect of anti-TB drug nanoparticle (NP) compounds in anti-TB regimens against MDR-TB remains unclear.

Objective: The objective of this article is to prepare levofloxacin, linezolid, ethambutol, prothionamide, and pyrazinamide encapsulated NPs and to evaluate their therapeutic efficacy against MDR-TB in macrophages.

Methods: Drug-loaded PLGA NPs were prepared by the multiple emulsion method. The colocalization, intracellular release, and anti-TB activity of these NPs were investigated on cultured macrophages. The immune phenotype of the macrophages, including their mitochondrial membrane potential, reactive oxygen species (ROS), and nitric oxide (NO) production, was evaluated following treatment with NPs or free drug compounds.

Results: All drug-loaded PLGA NPs were spherical in shape, 150 to 210 nm in size, and showed 14.22% to 43.51% encapsulation efficiencies and long-duration release. Drug-loaded PLGA NPs were mainly distributed in the cytoplasm of macrophages, showed high cellular compatibility, and maintained their concentration for at least 13 days. Compared with the free drug compounds, the number of colonies after exposure to PLGA NP compounds was significantly less. The enhanced antibacterial activity of the NP compounds may be due to the enhanced levels of ROS and NO and the increased early apoptosis stress within M. tuberculosis-infected macrophages additionally.

Conclusion: The application of PLGA NP compounds not only enhances drug efficacy but also induces innate bactericidal events in macrophages, confirming this as a promising approach for MDR-TB therapy.

Advancement in nanotechnology leads to the development of polysaccharides which are very efficient carriers in delivering therapeutic substances like drugs, proteins, and genes. This review describes the role of polysaccharides and their derivatives in the cellular targeting of genetic materials for the treatment of various biological disorders. Applications, challenges, advantages, and disadvantages of polysaccharides used in gene delivery are discussed in the manuscript. Cationic and natural polysaccharides are generally used for RNA and DNA delivery and exhibit better performance in gene transfection. After a substantial literature survey, it can be concluded that different polysaccharides and their derivatives are effectively used in the delivery of genetic material. Natural polysaccharides are widely used due to their advantageous properties like biocompatibility, biodegradability, and low toxicity in the biological environment.

Cancer immunotherapy has advanced significantly in recent years. Nanocarriers like liposomes can improve cancer immunotherapy and even stronger immune responses by improving cell type-specific distribution. Liposomes are lipid bilayer vesicles that are biodegradable and biocompatible and are often used as smart delivery systems for both hydrophobic and hydrophilic bioactive. Whereas the idea of employing liposomes for administering drugs has been known since the 1960s, the early 2000s saw continuing technological advances and formulations for drug entrapment and manufacturing. Modern deterministic studies have tried discovering more about how genetic material is delivered through liposomes. Liposomes' interactions with cells are still a bit of mystery. Liposome-mediated transmission of genetic material experiences systemic impediments perlysosomal degradation, endosomal escape, and nuclear uptake. Controlling the physical architecture and chemical properties of liposome structures, such as lipid-to-DNA charge, ester bond composition, size, and ligand complexation structure, is critical for targeting liposomes' success as vehicles for gene delivery. This analysis focuses on advancements in ligand-targeted liposomes and theranostic (diagnostic) liposomes for cancer diagnosis and treatment. This review will explore the numerous transgene mechanisms and molecular targets implicated in cancer cell death and the associated benefits of using liposomal formulations throughout the years. This sequence of breakthroughs will interest aspiring researchers and the pharmaceutical industry involved in liposome development.

Proteins and peptides possess considerable potential in treating solid tumors because of their unique properties. At present, there are over 100 peptide-based formulations on the market. Today, peptides and proteins are in more demand due to their selective nature and high target-binding efficiency. Targeting solid tumors with compounds of molecular weight less than 10 kDa are much more desirable because they undergo excessive penetration in view of the fact that they are small sized. The solid tumors have thick tissues and possess excessive interstitial fluid pressure, because of which high molecular compounds cannot enter. The properties of proteins and peptides induce low toxic effects and lessen the major side effects caused by chemical-based drugs. However, their delivery is quite challenging as most proteins and peptides stop functioning therapeutically when following a parenteral route of administration. This paper elaborates on the importance of new age formulations of peptides and proteins followed by their recently documented advancements that increase their stability and delay their metabolism, which helps to target solid tumors.

Introduction: The goal of this study was to see if ascorbic acid grafted polylactic glycolic acid-b-polyethylene glycol nanoparticles (PLGA-b-PEG NPs) might boost the carrying or transport capacity of rivastigmine(RSM) to the brain via choroid plexus Sodium-dependent vitamin C transporter 2 (SVCT2 transporters). The IR and 1H NMR, were used to characterise the PLGA-b-PEG copolymer.

Methods: Nanoprecipitation method was used to make PLGA-b-PEG NPs. To promote SVCT2- mediated transportation of ascorbic acid (Asc) into the brain, PLGA-b-PEG NPs of acceptable size, polydispersity, and drug loading were bound with ascorbic acid (PLGA-b-PEG-Asc). When compared to PLGA-b-mPEG NPs, the surface functionalization of NPs with ascorbic acid dramatically improved the cellular uptake of NPs in SVCT2 expressing NIH/3T3 cells. Radial Arm Maze Test, and Acetylcholinesterase (AChE) activity in scopolamine-induced amnetic rats were used to assess in vivo pharmacodynamic effectiveness.

Results: In vivo pharmacodynamic tests revealed that drug loaded PLGA-b-PEG-Asc NPs had much greater therapeutic and sustained activity than free drugs, and PLGA-b-mPEG NPs to the brain.

Conclusion: As a consequence, the findings revealed that using ascorbic acid grafted PLGA-b-PEG NPs to deliver bioactives to the brain is a potential strategy.

Background: The orally disintegrating tablets (ODTs) are especially suitable for elders and children with dysphagia, who need to be given customized dosages.

Objectives: This study aimed to prepare orally disintegrating tablets (ODTs) which can be customized as drug content by using semi-solid 3D printing pressure extrusion technology, with water insoluble and thermally unstable drug loratadine.

Methods: The influence of binder concentration, disintegrating agent dosage and ratio mannitol: cellulose on formability and disintegration time was investigated. The properties of orally disintegrating tablets were investigated by ATR-FTIR, XRPD, DSC and SEM. The correlation formula between tablet bottom area and drug content was established.

Results: The formulation was optimized, and contained loratadine 3 g, cellulose 4 g, mannitol 2 g, carboxy methyl starch sodium 1g, 6% PVP K30 16 ml. The disintegration time was less than 60 s with infilling percentage of 60%, and the disintegration time was less than 30 s with infilling percentage of 40%. There was no detectable interaction between loratadine and the selected excipients by the analysis of ATR-FTIR, DSC and XRPD. The structure of the tablets was porous, and the drug was dissolved completely within 10 min. The drug content (x) of the tablet and the bottom area (y) of the tablet showed a linear fitting relationship, y = 3.8603x - 0.7176, r² = 0.9993.

Conclusion: Semi-solid extrusion of 3D printing technology was applied to prepare loratadine orally disintegrating tablets with customized drug content, which provides an alternative method for the research of customized preparation.

Background: Celecoxib is generally used for the treatment of rheumatoid arthritis, however its poor bioavailability and cytotoxicity in pure form have reduced its therapeutic efficacy. This study aims to develop celecoxib liquid suppositories with improved bioavailability and reduced toxicity.

Methods: The celecoxib liquid suppositories were prepared by thoroughly mixing celecoxib, poloxamer 188 and poloxamer 407, and tween-20, respectively used as drug, polymers and surfactant, in triple distilled water using cold technique. The developed liquid suppositories were characterized in terms of their gelation temperature, gelation time, and gel strength. Moreover, the muco-adhesive force was determined for the suppositories. The release behavior of the liquid suppositories was investigated in distilled water and compared with drug suspension. Furthermore, pharmacokinetics and morphological studies were carried out in rats after rectal administration of the celecoxib liquid suppository compared with drug suspension.

Results: Poloxamer 188 and Tween-20 concentrations have significantly reduced the gelation temperature and time; however, the gel strength and bio-adhesive force were significantly enhanced. The concentration of celecoxib has no significant effect on the properties of liquid suppositories. A significantly enhanced and potentially sustained drug release was observed from the celecoxib liquid suppositories as compared with the drug suspension. The optimized formulation was easy to administer rectally because it quickly forms gel upon insertion into the body due to a suitable gelation temperature of about 31.7 °C. After rectal administration in rats, the celecoxib liquid suppository gave a significantly increased pharmacokinetic profile including enhanced plasma concentration and 9.7 fold improved area under the curve (AUC) compared to the drug suspension. Additionally, the morphology study exhibited no toxicity to the rectal tissue, no signs of irritation, or injury after the application of suppository. However, severe rectal tissue toxicity and irritation was observed in the suspension treated rectum.

Conclusion: It can be concluded that the liquid suppository system may significantly enhance the solubilization and bio-availability of sparingly water-soluble drugs as evident in the case of celecoxib with no toxicity at the site of application.

Purpose: The goal of the present research was to isolate a biopolymer from Phaseolus vulgaris (P. vulgaris) and Zea mays (Z. mays) plants and used it to construct Resveratrol (RES)-loaded translabial films.

Methods: Biopolymers were extracted from P. vulgaris and Z. mays seeds using a simple process. Separated biopolymers, sodium carboxymethylcellulose (SCMC) and tragacanth were subjected to formulation development by incorporating RES-loaded translabial films. The Fourier-transform infrared spectroscopy (FTIR), physical appearance, weight, thickness, folding endurance, swelling index, surface pH, percent moisture absorption, percent moisture loss, vapor transfer rate, and content uniformity of the translabial films were examined. The mucoadhesive, ex-vivo permeation, in vivo and stability studies, were performed.

Results: The results showed that RES-loaded translabial films produced from P. vulgaris and Z. mays biopolymers exhibited exceptional mucoadhesive, stability, and permeation properties. Results revealed that the best formulations were prepared from a combination of biopolymer (P. vulgaris C or Z. mays C) with tragacanth. Formulations with tragacanth revealed good swelling and thus permeation profiles. In vivo release of TL 11 was found to be 24.05 ng/ml in 10 hours and it was stable enough at 45°C.

Conclusion: This research suggested that RES-loaded translabial formulations can be potentially used for the treatment of Parkinson's disease with good patient compliance to geriatric and unconscious patients.

Nanotechnology has attracted researchers around the globe owing to the small size and targeting properties of the drug delivery vectors. The interest in self-nanoemulsifying drug delivery systems (SNEDDS) has shown an exponential increase from the formulator's point of view. SNEDDS have shown wide applicability in terms of controlled and targeted delivery of various types of drugs. They chemically consist of oil, surfactants and co-surfactants that decrease the emulsion particle size to the range of <100 nm. However, stability issues such as drug precipitation during storage, incompatibility of ingredients in shell, decrease their application for the long run and these issues have been highlighted in this paper. The current review throws limelight on the biological aspects and process parameters. In addition, the process of absorption from GI is also discussed in detail. SNEDDS have been utilized as a treatment option for various diseases like cancer, diabetes, and ocular and pulmonary diseases. Along with this, the authors highlight the advances involving in vivo and in vitro lipolysis studies on SNEDDS, also highlighting recent innovations in this field, such as novel combinations of drug-free solid SNEDDS + solid dispersions, lipid-modified chitosan containing mucoadhesive SNEDDS, pHsensitive SNEDDS and several others.

Background: Currently, the treatment protocols for tuberculosis (TB) have several challenges, such as inconsistent oral bioavailability, dose-related adverse effects, and off-target drug toxicity.

Methods: This research reports the design and characterization of rifampicin (RIF) and isoniazid (INH) loaded hybrid lipid-polysaccharide nanoparticles using the solvent injection method, and demonstrated the influence of conjugated mannosyl residue on macrophage targeting and intracellular drug delivery capacity.

Results: The nanospheres, herein called mannose-decorated lipopolysaccharide nanoparticles, were spherical in shape, exhibiting average sizes less than 120 nm (PDI<0.20) and positive zeta potentials. Drug encapsulation was greater than 50% for rifampicin and 60% for isoniazid. The pH-responsive drug release was sustained over a 48-hour period and preferentially released more rifampicin/isoniazid in a simulated acidic phagolysosomal environment (pH 4.8) than in a simulated physiological medium. TGA and FTIR analysis confirmed successful mannose-grafting on nanoparticle surface and optimal degree of mannosylation was achieved within 48-hour mannose-lipopolysaccharide reaction time. The mannosylated nanoparticles were biocompatible and demonstrated a significant improvement towards uptake by RAW 264.7 cells, producing higher intracellular RIF/INH accumulation when compared to the unmannosylated nanocarriers.

Conclusion: Overall, the experimental results suggested that mannose-decorated lipopolysaccharide nanosystems hold promise towards safe and efficacious macrophage-targeted delivery of anti-TB therapeutics.