Understanding lymphatic drug delivery through chylomicron blockade: A retrospective and prospective analysis DOI Creative Commons
Malaz Yousef, Nádia Araci Bou‐Chacra, Raimar Löbenberg

et al.

Journal of Pharmacological and Toxicological Methods, Journal Year: 2024, Volume and Issue: 129, P. 107548 - 107548

Published: Aug. 3, 2024

Scientists have developed and employed various models to investigate intestinal lymphatic uptake. One approach involves using specific blocking agents influence the chylomicron-mediated absorption of drugs. Currently utilized include pluronic L-81, puromycin, vinca alkaloids, colchicine, cycloheximide. This review offers a thorough analysis diverse utilized, evaluating existing reports while delineating gaps in current research. It also explores pharmacokinetic related aspects uptake pathway its blockage through discussed models. Pluronic L-81 has reversible effect, minimal toxicity, unique mode action. Yet, it lacks clinical on chylomicron blockage, likely due low concentrations used. Puromycin though documented for lack information their application drug Other alkaloids show promise affecting triglyceride profiles represent possible test as blockers. Colchicine cycloheximide, widely used pharmaceutical development, demonstrated efficacy, with cycloheximide preferred lower toxicity. However, further investigation into effective toxic doses colchicine humans is needed understand impact. The additionally followed complete journey oral targeting drugs from intake excretion, provided equation considering assessing bioavailability. Moreover, urinary data non-invasive way measure lymphatics was illustrated, likelihood interactions when blockers are human subjects underscored.

Language: Английский

Development and Preclinical Assessment of a Palbociclib Nanostructured Lipid Carrier for Potential Breast Cancer Management DOI

Nida Nehal,

Devika Unnithan,

Nasr A. Emad

et al.

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Breast cancer has the highest incidence rates among all cancers, which represent a global health concern. Effective chemotherapy for breast must minimize adverse effects to improve patient outcomes. Palbociclib (PB), CDK 4/6 inhibitor, restricts cell growth and suppresses DNA replication in retinoblastoma tumor suppressor gene (RB). Despite its breakthrough status postapproval, PB is associated with severe side effects, including neutropenia, leukopenia, infections, thrombocytopenia. The current study aims develop optimize PB-loaded lipidic nanocarrier. development method was solvent evaporation, formulation optimization performed using central composite rotatable design. Characterization of nanostructured lipid carrier (NLC) showed particle size 129.8 ± 7.6 nm PDI 0.2694 0.04 zeta potential −29.8 2.4 mV. Surface morphology studied transmission electron microscopy, confirmed particles' uniform spherical shape. In vitro release studies 0.1 N HCl pH 6.8 phosphate buffer demonstrated cumulative drug releases 91.23 2.1% 72.9 2.0%, respectively. Intestinal permeation 3.76-fold increase gut PB-NLC compared that PB-Sus. lipolysis indicated an enhanced availability at site absorption. Confocal revealed improved penetration depth intestine vivo pharmacokinetic incorporating into nanocarrier (PB-NLC) significantly bioavailability by approximately 5.9-fold (p < 0.05) suspension. Additionally, acute toxicity Wistar rats safety developed NLC oral administration managing cancer. Therefore, shows significant promise treatment, providing delivery minimized effects.

Language: Английский

Citations

1
Evasion of P-gp mediated efflux and enhancement of bioavailability of protease inhibitor lopinavir by lipidic nanocarriers decorated with TPGS DOI

Aashish Aashish,

Nida Nehal,

Saif Khan

et al.

Particulate Science And Technology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 17

Published: March 14, 2025

Lopinavir (LPV) presents significant challenges in HIV management due to its poor permeability and low solubility. This study focuses on the formulation, optimization, characterization of nanostructured lipid carriers (NLC) enriched with TPGS enhance delivery bioavailability antiretroviral drugs (ARDs). LPV-NLC was developed using a modified solvent emulsification method optimized by employing quality-by-design (QbD) approach. The NLC formulation incorporated TPGS, achieving globule size 99.19 ± 4.68 nm, high entrapment efficiency 90.2 2.8%, polydispersity index (PDI) 0.236 0.025. Ex-vivo studies demonstrated 1.67-fold increase flux, highlighting superiority LPV-TPGS-NLC over LPV-S. Pharmacokinetic evaluation revealed 3.40-fold enhancement for LPV-TPGS-NLC, peak plasma concentration (Cmax) 1320.03 79.12 ng/mL, approximately twice that These findings underscore potential TPGS-enriched as novel drug platform improving oral therapeutic efficacy LPV. enhanced achieved this could enable dose reduction, thereby minimizing associated side effects patient compliance therapy.

Language: Английский

Citations

0
Development and Optimization of Eberconazole Nanostructured Lipid Carrier Topical Formulations Based on the QbD Approach DOI
Amarnath Reddy Ramireddy, Dilip Kumar Behara

AAPS PharmSciTech, Journal Year: 2025, Volume and Issue: 26(4)

Published: March 18, 2025

Language: Английский

Citations

0
Deuteration Strategy-Inspired Design of Novel Diarylpyrimidine Derivatives as Potent Non-Nucleoside Reverse Transcriptase Inhibitors Featuring Improved Efficacy, Selectivity, and Druggability DOI
Kun Zhang, Tieling Xing, Li Ding

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 5, 2025

Deuteration strategy holds significant importance in the field of drug development. In this study, deuteration was applied to incorporate deuterated methyl groups at metabolic sites where were originally present, with expectation improving anti-HIV activity, safety, and druggability. Among compounds, exemplary compound 5a (ZK-316) exhibited potent broad-spectrum activity against wild-type clinically observed mutant strains, EC50 values ranging from 0.99 75.1 nM, surpassing that hit 3 (EC50 = 1.86-795.76 nM). Moreover, low cytotoxicity by ZK-316 (CC50 > 225 nM), which over 36.8 times lower than 3, high selectivity also shown. Not only there no apparent inhibition cytochrome P450 (CYP) enzymes, but human ether-à-go-go-related gene (hERG) toxicity found. And favorable pharmacokinetic profiles shown as well, a bioavailability 29%, all indicated its promising Additionally, identification metabolites carried out verify stability within liver microsomes. These results offer valuable insights into development non-nucleoside reverse transcriptase inhibitors (NNRTIs) for immunodeficiency virus (HIV) therapy.

Language: Английский

Citations

0
Enhancing lymphatic uptake of Darunavir Ethanolate through TPGS-enriched lipid nanocarriers for oral delivery DOI
Abdul Muheem, Ali Sartaj, Eman Aldosari

et al.

Particulate Science And Technology, Journal Year: 2024, Volume and Issue: 42(6), P. 988 - 1014

Published: March 3, 2024

Darunavir ethanolate (DRVE) is a promising molecule against wild-type protease inhibitors in human immunodeficiency virus (HIV) infection. It has 37% oral bioavailability. In this study, the d-alpha-Tocopheryl Polyethylene Glycol 1000 Succinate (TPGS)-decorated DRVE-loaded lipid nanocarriers (DRVE-TPGS-LNCs) were optimized via central composite rotatable design using modified solvent emulsification method. Various characteristic features of DRVE-TPGS-LNCs, such as globule size, polydispersity index, zeta potential, % entrapment efficiency, and drug loading, determined found to be 116.5 ± 2.52 nm, 0.269 0.0221, −10.8 0.265 mV, 94.31% 10.75%, 8.79% 0.937%, respectively. The spherical shape was evaluated by cryo-transmission electron microscopy. In-vitro study demonstrated cumulative release 81.70% 7.35% at pH 1.2 73.03% 7.17% 6.8 after 12 h study. Moreover, intestinal permeation confocal microscope studies revealed approximately two-fold increased nanoformulation across gut sac compared suspension, inhibition p-glycoprotein efflux also confirmed obtaining minimum ratio (0.253) formulation suspension. pharmacokinetic that relative bioavailability TPGS-DRVE-LNCs suspension 19.85 1.75 8.72 0.753 μg.h/mL, respectively, which 2.25-fold more than means threefold increase DRVE-TPGS-LNCs due improved lymphatic uptake inhibition. Thus, DRVE can meet need reduce high dose antiretroviral drugs minimize peripheral adverse reactions associated with dose-related burden.

Language: Английский

Citations

1
D-α-Tocopheryl Polyethylene Glycol Succinate-decorated dual drug-loaded lipidic nanocarriers: A Strategic approach for targeting lymphatic uptake and p-gp efflux modulation to enhance oral bioavailability in HIV-1 viral reservoirs DOI
Abdul Muheem, Mohd Waseem, Ali Sartaj

et al.

Journal of Drug Delivery Science and Technology, Journal Year: 2024, Volume and Issue: 98, P. 105831 - 105831

Published: June 6, 2024

Language: Английский

Citations

0
Understanding lymphatic drug delivery through chylomicron blockade: A retrospective and prospective analysis DOI Creative Commons
Malaz Yousef, Nádia Araci Bou‐Chacra, Raimar Löbenberg

et al.

Journal of Pharmacological and Toxicological Methods, Journal Year: 2024, Volume and Issue: 129, P. 107548 - 107548

Published: Aug. 3, 2024

Scientists have developed and employed various models to investigate intestinal lymphatic uptake. One approach involves using specific blocking agents influence the chylomicron-mediated absorption of drugs. Currently utilized include pluronic L-81, puromycin, vinca alkaloids, colchicine, cycloheximide. This review offers a thorough analysis diverse utilized, evaluating existing reports while delineating gaps in current research. It also explores pharmacokinetic related aspects uptake pathway its blockage through discussed models. Pluronic L-81 has reversible effect, minimal toxicity, unique mode action. Yet, it lacks clinical on chylomicron blockage, likely due low concentrations used. Puromycin though documented for lack information their application drug Other alkaloids show promise affecting triglyceride profiles represent possible test as blockers. Colchicine cycloheximide, widely used pharmaceutical development, demonstrated efficacy, with cycloheximide preferred lower toxicity. However, further investigation into effective toxic doses colchicine humans is needed understand impact. The additionally followed complete journey oral targeting drugs from intake excretion, provided equation considering assessing bioavailability. Moreover, urinary data non-invasive way measure lymphatics was illustrated, likelihood interactions when blockers are human subjects underscored.

Language: Английский

Citations

0