Folate decorated chitosan-chondroitin sulfate nanoparticles loaded hydrogel for targeting macrophages against rheumatoid arthritis.

Inflammatory cell infiltration, particularly macrophages, plays a major contribution to the pathogenesis of Rheumatoid Arthritis (RA). Exploiting the overexpression of folate receptors (FR-ß) on these recruited macrophages has gained significant attraction for ligand-targeted delivery. Leflunomide (LEF), being an immunomodulatory agent is considered the cornerstone of the therapy, however, its oral efficacy is impeded by low solubility and escalating adverse effects profile. Therefore, in the present work, we developed Folate-conjugated chitosan-chondroitin sulfate nanoparticles encapsulating LEF for selective targeting at inflammatory sites in RA. For this purpose, the folate group was first conjugated with the chitosan polymer. After which, Folate Leflunomide Nanoparticles (FA-LEF-NPs) were synthesized through the ionotropic gelation method by employing FA-CHI and CHS. The polymers CHI and CHS were also presented with innate anti-inflammatory and anti-rheumatic attributes that were helpful in provision of synergistic effects to the formulation. These nanoparticles were further fabricated into a hydrogel, employing almond oil (A.O) as a permeation enhancer. The in vivo studies justified the preferential accumulation of FA-conjugated nanoparticles at inflamed joints more than any other organ in comparison to the free LEF and LEF-NPs formulation. The FA-LEF-NPs loaded hydrogel also ascertained a minimal adverse effect profile with an improvement of inflammatory cytokines expression.

Development and validation of HPLC method for simultaneous determination of Leflunomide and folic acid in the nanoparticulate system by reversed-phase HPLC.

OBJECTIVE: The main objective of this study was to develop a highly sensitive, accurate, and reproducible analytical method for the simultaneous detection of LEF and FA in polymeric nanocarriers. SIGNIFICANCE: Leflunomide (LEF), is widely employed in the treatment of rheumatoid arthritis (RA). However, long-term delivery of the drug is associated with systemic side effects. Therefore, folate (FA) conjugated LEF nanocarriers were fabricated for targeting the nanocarriers toward activated macrophages. HPLC is considered one of the most sensitive and precise analytical techniques for the simultaneous detection and estimation of different components in a particular sample. METHODS: Analysis was performed on HPLC (Shimadzu 10 A), having a reversed-phase C-18 column (Beckmen, 250 X 4.6 mm, 5 µm) equipped with a photodiode detector set at a wavelength of 260 nm (LEF) and 285 nm (Folic acid). The isocratic mobile phase was composed of acetonitrile, water, and trimethylamine in a ratio of 65:35:0.5 at pH 4. Rapid analysis of both agents was performed, with a total run time of 10 min (FA = 2.1 ± 0.1 min, LEF = 5.9 ± 1 min) at a 1 mL/min flow rate. RESULTS: The assay demonstrated good linearity of 0.9989 of 0.9997 for LEF and FA respectively with a recovery in the range of 95-100%. The method also depicted good specificity, and intra and inter-day precision based on relative standard deviation (RSD) values. CONCLUSIONS: The study concludes, that the developed method was helpful in the detection and quantitation of lower values of both agents from polymeric nanocarriers.

HighlightsOptimization and validation of the RP-HPLC method were performed for the simultaneous detection of LEF and FA.Validation was performed on the basis of linearity, accuracy, precision, LOD, LOQ, and robustness in accordance with ICH criteria.Validated analytical procedure was employed for the simultaneous detection of LEF and FA from polymeric nanocarriers.The proposed analytical method is reliable, fast, robust, and can be successfully applied for quantification of % EE, and % DL in polymeric nanocarriers.

Exploiting Recent Trends in the Treatment of Androgenic Alopecia through Topical Nanocarriers of Minoxidil.

Androgenic alopecia, a polygenetic disorder, is characterized by well-defined hair loss that progresses gradually. The disease affects both males and females and exerts a drastic impact on a person's psychological well-being. Minoxidil (MIN) is the commonly prescribed FDA-approved agent for the treatment of disease. It is conventionally administered as a topical solution but is allied with several adverse reactions, such as erythema and dermatitis, resulting in decreased patient compliance. To overcome these side effects, researchers developed various nanocarriers of MIN. Encapsulation of MIN in various nanocarriers enhances the entry of the drug into hair follicles and results in the formation of reservoirs for controlled delivery of the drug. It also increases the therapeutic outcomes in comparison to conventional formulations. The present review discusses the composition and physicochemical properties of different nanocarrier systems of MIN. Although successful encapsulation of MIN has been observed in these nanocarriers, there is still scarce data regarding their loading in a final dosage form. This allows researchers to conduct more in vivo studies and focus on their clinical applications. HIGHLIGHTS: • Androgenic alopecia is a polygenetic disorder with gradual loss of hair that progresses with age. • Minoxidil An FDA-approved drug for the treatment of androgenic alopecia. • Is allied with several adverse reactions, having decreased therapeutic efficacy. • Several nanocarriers including polymeric lipid-based and inorganic nanoparticles have been developed to improve their therapeutic efficacy. • Utilization of these nanocarriers results in increased retention of MIN within the hair follicles and utilizes low concentrations of solvents. • Modifications of different physicochemical properties of these carriers I.e. Particle size Zeta potential and entrapment efficiency are important to attain the above objectives.

Chitosan nanocarriers for microRNA delivery and detection: A preliminary review with emphasis on cancer.

In recent years, gene therapy based on miRNA has been employed as a potential growing technique for treating various co-morbidities. Direct administration of miRNA is unrealistic due to their lower specificity, stability, and decreased penetration through the cellular membrane. Suitable delivery vectors must be required to deliver miRNA efficiently. Non-viral vectors can be composed of polymeric, lipids, or inorganic components/nanocarriers. Among different cationic polymers, chitosan nanocarriers are effectively utilized to deliver miRNA owing to its cationic nature, biodegradability, biocompatibility, and increased potential for functional modifications. Therefore, chitosan has been widely employed to effectively deliver several miRNAs to the target site. This review will discuss the recent signs of progress and future perspectives in delivering and detecting miRNAs via chitosan and its derivatives with an emphasis on cancer. The review will also provide an insight into the various challenges of these chitosan carriers to be used as delivery agents for miRNA.

Exploiting recent trends for the synthesis and surface functionalization of mesoporous silica nanoparticles towards biomedical applications.

Rapid progress in developing multifunctional nanocarriers for drug delivery has been observed in recent years. Inorganic mesoporous silica nanocarriers (MSNs), emerged as an ideal candidate for gene/drug delivery with distinctive morphological features. These ordered carriers of porous nature have gained unique attention due to their distinctive features. Moreover, transformation can be made to these nanocarriers in terms of pores size, pores volume, and particle size by altering specific parameters during synthesis. These ordered porous materials have earned special attention as a drug carrier for treating multiple diseases. Herein, we highlight the strategies employed in synthesizing and functionalizing these versatile nanocarriers. In addition, the various factors that influence their sizes and morphological features were also discussed. The article also summarizes the recent advancements and strategies for drug and gene delivery by rendering smarter MSNs by incorporating functional groups on their surfaces. Averting off-target effects through various capping strategies is a massive milestone for the induction of stimuli-responsive nanocarriers that brings out a great revolution in the biomedical field.

Development, optimisation, and evaluation of nanoencapsulated diacerein emulgel for potential use in osteoarthritis.

AIM: This study aimed to utilise the proficient function of diacerein (DCR) and anti-inflammatory polymers to develop sustained release nanoencapsulated emulgel for potential use in osteoarthritis (OA). METHODS: Chitosan (CHS) and chondroitin sulphate (CS) were employed as natural anti-inflammatory polymers to encapsulate nanoformulation of DCR. Optimised nanoformulation was prepared and characterised by investigating impact of polymers and surfactant on particle size, PDI, and encapsulation efficiency (EE). Afterwards, nanoemulgel of optimised DCR-NPs was formulated and evaluated for transdermal application. RESULTS: Optimised nanoformulation depicted spherical shape with particle size of 320 nm having PDI and EE of 0.3 ± 0.07 and 82 ± 4% (w/w), respectively. DCR-nanoemulgel depicts sustained action of drug up to 96 h with enhanced permeation activity and non-irritancy index. CONCLUSIONS: The elaborated nanoemulgel sustained release of drug having superior penetration properties with provision of enhanced therapeutic effect owing to the presence of CHS, CS, and Argan oil possessing indelible anti-inflammatory attributes.