Pharmacokinetics and tissue distribution of hydrazinocurcumin in rats

Satyavert,; Gupta, Sumeet; Choudhury, Hira; Jacob, Shery; Nair, Anroop B.; Dhanawat, Meenakshi; Munjal, Kavita

doi:10.1007/s43440-021-00312-5

Cited by 17 publications

(9 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DTX concentrations were measured using the previously indicated verified and calibrated HPLC technique. Mean plasma concentration vs. time profile was represented graphically, and the area under the curve (AUC) was calculated [ 39 ] for comparison purposes.…”

Section: Methodsmentioning

confidence: 99%

Adenosine Conjugated Docetaxel Nanoparticles—Proof of Concept Studies for Non-Small Cell Lung Cancer

Aldawsari

Singh²,

Alhakamy

et al. 2022

Pharmaceuticals

View full text Add to dashboard Cite

Non-small cell lung cancer, a molecularly diverse disease, is the most prevalent cause of cancer mortality globally. Increasing understanding of the clinicopathology of the disease and mechanisms of tumor progression has facilitated early detection and multimodal care. Despite the advancements, survival rates are extremely low due to non-targeted therapeutics and correspondingly increased risk of metastasis. At some phases of cancer, patients need to face the ghost of chemotherapy. It is a difficult decision near the end of life. Such treatments have the capability to prolong survival or reduce symptoms, but can cause serious adverse effects, affecting quality of life of the patient. It is evident that many patients do not die from burden of the disease alone, but they die due to the toxic effect of treatment. Thus, increasing the efficacy is one aspect and decreasing the toxicity is another critical aspect of cancer formulation design. Through our current research, we tried to uncover both mentioned potentials of the formulation. Therefore, we designed actively targeted nanoparticles for improved therapeutics considering the overexpression of adenosine (ADN) receptors on non-small cell lung cancer (NSCLC) cells. Docetaxel (DTX), an essential therapeutic as part of combination therapy or as monotherapy for the treatment of NSCLC, was encapsulated in biodegradable poly(lactic-co-glycolic acid) nanoparticles. ADN was conjugated on the surface of nanoparticles using EDC-NHS chemistry. The particles were characterized in vitro for physicochemical properties, cellular uptake, and biocompatibility. The size and zeta potential of DTX nanoparticles (DPLGA) were found to be 138.4 ± 5.45 nm and −16.7 ± 2.3 mV which were found to change after ADN conjugation. The size was increased to 158.2 ± 6.3 nm, whereas zeta potential was decreased to −11.7 ± 1.4 mV for ADN-conjugated DTX nanoparticles (ADN-DPLGA) indicative of surface conjugation. As observed from transmission electron microscopy (TEM), the nanoparticles were spherical and showed no significant change in encapsulation efficiency even after surface conjugation. Careful and systematic optimization leads to ADN-conjugated PLGA nanoparticles having distinctive characteristic features such as particle size, surface potential, encapsulation efficacy, etc., that may play crucial roles in the fate of nanoparticles (NPs). Consequently, higher cellular uptake in the A549 lung cancer cell line was exhibited by ADN-DPLGA compared to DPLGA, illustrating the role of ADN receptors (ARs) in facilitating the uptake of NPs. Further in vivo pharmacokinetics and tissue distribution experiments revealed prolonged circulation in plasma and significantly higher lung tissue distribution than in other organs, dictating the targeting potential of the developed formulation over naïve drug and unconjugated formulations. Further, in vivo acute toxicity was examined using multiple parameters for non-toxic attributes of the developed formulation compared to other non-targeted organs. Further, it also supports the selection of biocompatible polymers in the formulation. The current study presents a proof-of-concept for a multipronged formulation technology strategy that might be used to maximize anticancer therapeutic responses in the lungs in the treatment of NSCLC. An improved therapeutic and safety profile would help achieve maximum efficacy at a reduced dose that would eventually help reduce the toxicity.

show abstract

Section: Methodsmentioning

confidence: 99%

Adenosine Conjugated Docetaxel Nanoparticles—Proof of Concept Studies for Non-Small Cell Lung Cancer

Aldawsari

Singh²,

Alhakamy

et al. 2022

Pharmaceuticals

View full text Add to dashboard Cite

show abstract

“…The mean recovery of drugs from plasma and brain were 97.68 and 94.22%, respectively. Various pharmacokinetic parameters, such as C max , T max , and AUC 0-t , were estimated by noncompartmental analysis [ 62 ].…”

Section: Methodsmentioning

confidence: 99%

Intranasal Delivery of Darunavir-Loaded Mucoadhesive In Situ Gel: Experimental Design, In Vitro Evaluation, and Pharmacokinetic Studies

Nair

Chaudhary²,

Shah³

et al. 2022

Gels

Self Cite

View full text Add to dashboard Cite

The clinical efficacy of antiretroviral therapy in NeuroAIDS is primarily limited by the low perfusion of the drug to the brain. The objective of the current investigation was to design and develop an in situ mucoadhesive gel loaded with darunavir to assess the feasibility of brain targeting through the intranasal route. Preliminary batches (F1–F9) were prepared and evaluated for various pharmaceutical characteristics. A full factorial design of the experiment was applied to optimize and assess the effect of two influencing variables (Carbopol 934P (X1) and Poloxamer 407 (X2)) on the response effects (gelation temperature (Y1) and % drug release (Y2) at 8 h). The data demonstrate that both influencing variables affect the response variables significantly (p < 0.05). The optimized formulation (F7) exhibited favorable rheological properties, adequate mucoadhesion, sustained drug release, and greater permeation across the nasal mucosa. An in vitro ciliotoxicity study confirms the nontoxicity of the optimized in situ gel (D7) on the nasal mucosa. An in vivo pharmacokinetic study in rats was performed to assess drug targeting to the brain following the nasal application of the selected in situ gel (D7). Significantly higher (p < 0.0001) Cmax (~4-fold) and AUC0-α (~3.5-fold) values were noticed in the brain after nasal application, as compared to the intravenous route. However, less systemic exposure to darunavir was noticed with nasal therapy, which confirms the low absorption of the drug into the central compartment. Overall, the data here demonstrate that the optimized in situ mucoadhesive nasal gel is effective in targeting darunavir to the brain by the nasal route and could be a viable option for the treatment of NeuroAIDS.

show abstract

“…The SNEDDS formulation (1 mL) was placed in a previously hydrated dialysis bag (Spectra/Por 4, diameter 25 mm, MW cut-off: 12,000-14,000 Spectrum Inc., Los Angeles, CA, USA). Aliquot volume (1 mL) of the samples was removed at regular time points (5,10,15,30,45, and 60 min) and an equivalent amount of medium was replaced. The samples taken were diluted suitably, filtered through a 0.2 µm Millex syringe-driven filter unit, and analyzed by HPLC.…”

Section: Screening Of Formulations By Full Factorial Designmentioning

confidence: 99%

“…The formulation was prepared as a suspension in 0.5% w/v carboxymethyl cellulose and administered to rats orally as a single dose by intragastric gavage in both groups. A blood sample (~200 µL) was drawn at predefined time points (1, 2, 4, 6, 9, 12, and 24 h) post-dosing from retroorbital plexus of individual rat under anesthesia using isoflurane [45]. Samples were collected in heparin pre-coated tubes and proteins were subsequently precipitated with a similar volume of acetonitrile [46].…”

Section: Oral Bioavailability Studiesmentioning

confidence: 99%

“…The filtrate (50 µL) was injected into the HPLC system whilst the sample taken at zero time was considered as the baseline value during analysis. The pharmacokinetic parameters of interest included area under the concentration-time curve (AUC 0t ), peak concentration (C max ), and time to reach peak concentration (T max ) and were determined by non-compartmental analysis described elsewhere [45].…”

Section: Oral Bioavailability Studiesmentioning

confidence: 99%

See 1 more Smart Citation

Formulation and Evaluation of Self-Nanoemulsifying Drug Delivery System Derived Tablet Containing Sertraline

et al. 2022

Self Cite

View full text Add to dashboard Cite

Being a biopharmaceutics classification system class II drug, the absorption of sertraline from the gut is mainly limited by its poor aqueous solubility. The objective of this investigation was to improve the solubility of sertraline utilizing self-nanoemulsifying drug delivery systems (SNEDDS) and developing it into a tablet dosage form. Ternary phase diagrams were created to identify nanoemulsion regions by fixing oil (glycerol triacetate) and water while varying the surfactant (Tween 80) and co-surfactant (PEG 200) ratio (Smix). A three-factor, two-level (23) full factorial design (batches F1–F8) was utilized to check the effect of independent variables on dependent variables. Selected SNEDDS (batch F4) was solidified into powder by solid carrier adsorption method and compressed into tablets. The SNEDDS-loaded tablets were characterized for various pharmaceutical properties, drug release and evaluated in vivo in Wistar rats. A larger isotropic region was noticed with a Smix ratio of 2:1 and the nanoemulsion exhibited good stability. Screening studies’ data established that all three independent factors influence the dependent variables. The prepared tablets displayed optimal pharmaceutical properties within acceptable limits. In vitro sertraline release demonstrated from solid SNEDDS was statistically significant (p < 0.0001) as compared to pure sertraline. Differential Scanning Calorimetry and X-Ray Diffraction data established the amorphous state of the drug in SNEDDS formulation, while FTIR spectra indicate the compatibility of excipients and drug. Pharmacokinetic evaluation of the SNEDDS tablet demonstrated significant increment (p < 0.0001) in AUC0-α (~5-folds), Cmax (~4-folds), and relative bioavailability (386%) as compared to sertraline suspension. The current study concludes that the solid SNEDDS formulation could be a practicable and effective strategy for oral therapy of sertraline.

show abstract

Pharmacokinetics and tissue distribution of hydrazinocurcumin in rats

Cited by 17 publications

References 47 publications

Adenosine Conjugated Docetaxel Nanoparticles—Proof of Concept Studies for Non-Small Cell Lung Cancer

Adenosine Conjugated Docetaxel Nanoparticles—Proof of Concept Studies for Non-Small Cell Lung Cancer

Intranasal Delivery of Darunavir-Loaded Mucoadhesive In Situ Gel: Experimental Design, In Vitro Evaluation, and Pharmacokinetic Studies

Formulation and Evaluation of Self-Nanoemulsifying Drug Delivery System Derived Tablet Containing Sertraline

Contact Info

Product

Resources

About