Qbd based and Box-Behnken design assisted Oral delivery of stable lactone (active) form of Topotecan as PLGA nanoformulation: Cytotoxicity, pharmacokinetic, in vitro, and ex vivo gut permeation studies

Khuroo, Tahir; Khuroo, Arshad; Hussain, Afzal; Mirza, Mohd Aamir; Panda, Amulya K.; Wani, Javid; Iqbal, Zeenat

doi:10.1016/j.jddst.2022.103850

Cited by 7 publications

(9 citation statements)

References 21 publications

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“…The other factors were kept constant as some of the process parameters (PPs) were optimized during the screening of the trial formulations. Three CMAs such as PLGA polymer (X1), surfactant (X2), and drug (X3) were taken as independent factors, where five levels were generated in the CCD, as mentioned in ESI, Table S4 † 23.…”

Section: Resultsmentioning

confidence: 99%

“…Three CMAs such as PLGA polymer (X1), surfactant (X2), and drug (X3) were taken as independent factors, where five levels were generated in the CCD, as mentioned in ESI, Table S4. † 23 …”

Section: Resultsmentioning

confidence: 99%

“…For the validation of the CCD model regarding our predicted goals, the bi-formulation was further post-analyzed in triplicate for the development of an accurate and precisely optimized formulation. 23 …”

Section: Methodsmentioning

confidence: 99%

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In silico and in vitro assessment of an optimized QbD-guided myoinositol and metformin-loaded mucus-penetrating particle-based gel for the amelioration of PCOS

Farooq,

Mirza,

Alshetaili

et al. 2024

Nanoscale Adv.

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Section: Resultsmentioning

confidence: 99%

“…Three CMAs such as PLGA polymer (X1), surfactant (X2), and drug (X3) were taken as independent factors, where five levels were generated in the CCD, as mentioned in ESI, Table S4. † 23 …”

Section: Resultsmentioning

confidence: 99%

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In silico and in vitro assessment of an optimized QbD-guided myoinositol and metformin-loaded mucus-penetrating particle-based gel for the amelioration of PCOS

Farooq,

Mirza,

Alshetaili

et al. 2024

Nanoscale Adv.

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“…The nasal mucosa composition, the viscosity of the nasal formulation, mucoadhesiveness, residence time, and nasal pH are major critical factors responsible for controlled drug release and permeation across the nasal epithelium [ 37 , 38 ]. The study was conducted for up to 6 h to avoid any loss of natural anatomical structural integrity of mucosal tissue and tissue viability [ 39 ]. The study was conducted using a simulated nasal fluid with pH 6.8 (to mimic nasal pH) to avoid nasal irritation and discomfort after application [ 40 ].…”

Section: Resultsmentioning

confidence: 99%

GastroPlus- and HSPiP-Oriented Predictive Parameters as the Basis of Valproic Acid-Loaded Mucoadhesive Cationic Nanoemulsion Gel for Improved Nose-to-Brain Delivery to Control Convulsion in Humans

Hussain

Altamimi

Ramzan

et al. 2023

Gels

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Oral and parenteral delivery routes of valproic acid (VA) are associated with serious adverse effects, high hepatic metabolism, high clearance, and low bioavailability in the brain. A GastroPlus program was used to predict in vivo performance of immediate (IR) and sustained release (SR) products in humans. HSPiP software 5.4.08 predicted excipients with maximum possible miscibility of the drug. Based on the GastroPlus and HSPiP program, various excipients were screened for experimental solubility, nanoemulsions, and respective gel studies intended for nasal-to-brain delivery. These were characterized by size, size distribution, polydispersity index, zeta potential, morphology, pH, % transmittance, drug content, and viscosity. In vitro drug release, ex vivo permeation profile (goat nasal mucosa), and penetration studies were conducted. Results showed that in vivo oral drug dissolution and absorption were predicted as 98.6 mg and 18.8 mg, respectively, from both tablets (IR and SR) at 8 h using GastroPlus. The predicted drug access to the portal vein was substantially higher in IR (115 mg) compared to SR (82.6 mg). The plasma drug concentration–time profile predicted was in good agreement with published reports. The program predicted duodenum and jejunum as the prime sites of the drug absorption and no effect of nanonization on Tmax for sustained release formulation. Hansen parameters suggested a suitable selection of excipients. The program recommended nasal-to-brain delivery of the drug using a cationic mucoadhesive nanoemulsion. The optimized CVE6 was associated with the optimal size (113 nm), low PDI (polydispersity index) (0.26), high zeta potential (+34.7 mV), high transmittance (97.8%), and high strength (0.7% w/w). In vitro release and ex vivo permeation of CVE6 were found to be substantially high as compared to anionic AVE6 and respective gels. A penetration study using confocal laser scanning microscopy (CLSM) executed high fluorescence intensity with CVE6 and CVE6-gel as compared to suspension and ANE6. This might be attributed to the electrostatic interaction existing between the mucosal membrane and nanoglobules. Thus, cationic nanoemulsions and respective mucoadhesive gels are promising strategies for the delivery of VA to the brain through intransal administration for the treatment of seizures and convulsions.

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“…The drug was quantified using HPLC at 254 nm. The study was conducted up to 180 min to avoid the loss of the natural integrity of tissue and tissue viability [ 17 ]. The study was replicated to obtain mean value.…”

Section: Methodsmentioning

confidence: 99%

Mechanistic of Vesicular Ethosomes and Elastic Liposomes on Permeation Profiles of Acyclovir across Artificial Membrane, Human Cultured EpiDerm, and Rat Skin: In Vitro-Ex Vivo Study

Hussain,

Altamimi,

Afzal

et al. 2023

Pharmaceutics

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Acyclovir (ACV) controls cutaneous herpes, genital herpes, herpes keratitis, varicella zoster, and chickenpox. From previously reported ACV formulations, we continued to explore the permeation behavior of the optimized ACV loaded optimized ethosome (ETHO2R) and elastic liposome (ELP3R) and their respective carbopol gels across artificial membrane, cultured human EpiDerm, and rat skin. Transepidermal water loss (TEWL), scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and atomic force microscopy (AFM) were used to investigate the mechanistic perspective of permeation behavior. The size values of reformulated ELP3-R and ETHO2-R were observed as 217 and 128 nm, respectively (close to previous report), whereas their respective gels showed as 231 and 252 nm, respectively. ETHO2R showed high elasticity, %EE, and low vesicle size. These were investigated for the diffusion rate of the drug permeation (3 h) across the artificial membrane, cultured human EpiDerm, and rat skin. ETHO2GR showed the highest permeation flux (78.42 µg/cm2/h), diffusion coefficient (8.24 × 10−5 cm2/h), and permeation coefficient (0.67 × 10−3 cm/h) of ACV across synthetic membrane, whereas diffusion coefficient (2.4 × 10−4 cm2/h) and permeation coefficient (0.8 × 10−3 cm/h) were maximum across EpiDerm for ETHO2GR. ETHO2R suspension showed maximized permeation flux (169.58 µg/cm2/h) and diffusion rate (0.293 mg/cm2/h1/2), suggesting the rapid internalization of vesicles with cultured skin cells at low viscosity. A similar observation was revealed using rat skin, wherein the permeation flux (182.42 µg/cm2/h), permeation coefficient (0.3 × 10−2 cm/h), and diffusion rate (0.315 mg/cm2/h1/2) of ETHO2R were relatively higher than ELP3R and ELP3GR. Relative small size (128 nm), low viscosity, ethanol-mediated ultra-deformability, high drug entrapment (98%), and elasticity (63.2) are associated with ETHO2R to provide remarkable permeation behavior across the three barriers. The value of TEWL for ETHO2R (21.9 g/m2h) was 3.71 times higher than untreated control (5.9 g/m2h), indicating ethanol-mediated maximized surficial skin lipid perturbation at 3 h of application, whereas the respective ETHO2GR-treated rat skin had TEWL value (18.6 g/m2h) slightly lower than ETHO2R due to gel-based hydration into the skin. SEL, CLSM, and AFM provided a mechanistic perspective of ETHO2R and ELP3R-mediated permeation across rat skin and carrier-mediated visualization (skin–vesicle interaction). AFM provided detailed nanoscale surface roughness topographical parameters of treated and untreated rat skin as supportive data to SEM and CLSM. Thus, ethosomes ETHO2R and respective gel assisted maximum permeation of ACV across rat skin and cultured human EpiDerm to control cutaneous herpes infection and herpes keratitis.

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Qbd based and Box-Behnken design assisted Oral delivery of stable lactone (active) form of Topotecan as PLGA nanoformulation: Cytotoxicity, pharmacokinetic, in vitro, and ex vivo gut permeation studies

Cited by 7 publications

References 21 publications

In silico and in vitro assessment of an optimized QbD-guided myoinositol and metformin-loaded mucus-penetrating particle-based gel for the amelioration of PCOS

In silico and in vitro assessment of an optimized QbD-guided myoinositol and metformin-loaded mucus-penetrating particle-based gel for the amelioration of PCOS

GastroPlus- and HSPiP-Oriented Predictive Parameters as the Basis of Valproic Acid-Loaded Mucoadhesive Cationic Nanoemulsion Gel for Improved Nose-to-Brain Delivery to Control Convulsion in Humans

Mechanistic of Vesicular Ethosomes and Elastic Liposomes on Permeation Profiles of Acyclovir across Artificial Membrane, Human Cultured EpiDerm, and Rat Skin: In Vitro-Ex Vivo Study

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