Drug-loaded sickle cells programmed ex vivo for delayed hemolysis target hypoxic tumor microvessels and augment tumor drug delivery

Background and Objectives: To develop electro-sensitive transdermal drug delivery systems (ETDDS) using polyacrylamide-grafted-pectin (PAAm-g-PCT) copolymer hydrogel for rivastigmine delivery. Methods: Free radical polymerization and alkaline hydrolysis technique was employed to synthesize PAAm-g-PCT copolymer hydrogel. The PAAm-g-PCT copolymeric hydrogel was used as a reservoir and cross-linked blend films of PCT and poly(vinyl alcohol) as rate-controlling membranes (RCMs) to prepare ETDDS. Results: The pH of the hydrogel reservoir was found to be in the range of 6.81 to 6.93 and drug content was 89.05 to 96.29%. The thickness of RCMs was in the range of 51 to 99 μ and RCMs showed permeability behavior against water vapors. There was a reduction in the water vapor transmission rate as the glutaraldehyde (GA) concentration was increased. The drug permeation rate from the ETDDS was enhanced under the influence of electric stimulus against the absence of an electric stimulus. The increase in flux by 1.5 fold was recorded with applied electric stimulus. The reduction in drug permeability observed when the concentration of GA was increased. Whereas, the permeability of the drug was augmented as an electric current was changed from 2 to 8 mA. The pulsatile drug release under “on– off” cycle of electric stimulus witnessed a faster drug release under ‘on’ condition and it was slow under ‘off’ condition. The alteration in skin composition after electrical stimulation was confirmed through histopathology studies. Conclusion: The PAAm-g-PCT copolymer hydrogel is a useful carrier for transdermal drug delivery activated by an electric signal to provide on-demand release of rivastigmine.

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Development and Evaluation of Docetaxel-Phospholipid Complex Loaded Self-Microemulsifying Drug Delivery System: Optimization and In Vitro/Ex Vivo Studies

Pharmaceutics ◽

10.3390/pharmaceutics12060544 ◽

2020 ◽

Vol 12 (6) ◽

pp. 544

Author(s):

Miao Wang ◽

Sung-Kyun You ◽

Hong-Ki Lee ◽

Min-Gu Han ◽

Hyeon-Min Lee ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Anticancer Agents ◽

Lipid Membrane ◽

Ex Vivo ◽

System Optimization ◽

Raw Material ◽

Phospholipid Complex ◽

Low Solubility

Docetaxel (DTX) has clinical efficacy in the treatment of breast cancer, but it is difficult to develop a product for oral administration, due to low solubility and permeability. This study focused on preparing a self-microemulsifying drug delivery system (SME) loaded with DTX-phospholipid complex (DTX@PLC), to improve the dissolution and gastrointestinal (GI) permeability of DTX. A dual technique combining the phospholipid complexation and SME formulation described as improving upon the disadvantages of DTX has been proposed. We hypothesized that the complexation of DTX with phospholipids can improve the lipophilicity of DTX, thereby increasing the affinity of the drug to the cell lipid membrane, and simultaneously improving permeability through the GI barrier. Meanwhile, DTX@PLC-loaded SME (DTX@PLC-SME) increases the dissolution and surface area of DTX by forming a microemulsion in the intestinal fluid, providing sufficient opportunity for the drug to contact the GI membrane. First, we prepared DTX@PLC-SME by combining dual technologies, which are advantages for oral absorption. Next, we optimized DTX@PLC-SME with nanosized droplets (117.1 nm), low precipitation (8.9%), and high solubility (33.0 mg/g), which formed a homogeneous microemulsion in the aqueous phase. Dissolution and cellular uptake studies demonstrated that DTX@PLC-SME showed 5.6-fold higher dissolution and 2.3-fold higher DTX uptake in Caco-2 cells than raw material. In addition, an ex vivo gut sac study confirmed that DTX@PLC-SME improved GI permeability of DTX by 2.6-fold compared to raw material. These results suggested that DTX@PLC-SME can significantly overcome the disadvantages of anticancer agents, such as low solubility and permeability.

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Harnessing Extracellular Matrix Biology for Tumor Drug Delivery

Journal of Personalized Medicine ◽

10.3390/jpm11020088 ◽

2021 ◽

Vol 11 (2) ◽

pp. 88

Author(s):

Nithya Subrahmanyam ◽

Hamidreza Ghandehari

Keyword(s):

Drug Delivery ◽

Extracellular Matrix ◽

Cancer Progression ◽

Active Role ◽

Reciprocal Relationship ◽

Design Parameters ◽

Cancer Etiology ◽

Cell Life ◽

Tumor Drug Delivery ◽

Signaling Interactions

The extracellular matrix (ECM) plays an active role in cell life through a tightly controlled reciprocal relationship maintained by several fibrous proteins, enzymes, receptors, and other components. It is also highly involved in cancer progression. Because of its role in cancer etiology, the ECM holds opportunities for cancer therapy on several fronts. There are targets in the tumor-associated ECM at the level of signaling molecules, enzyme expression, protein structure, receptor interactions, and others. In particular, the ECM is implicated in invasiveness of tumors through its signaling interactions with cells. By capitalizing on the biology of the tumor microenvironment and the opportunities it presents for intervention, the ECM has been investigated as a therapeutic target, to facilitate drug delivery, and as a prognostic or diagnostic marker for tumor progression and therapeutic intervention. This review summarizes the tumor ECM biology as it relates to drug delivery with emphasis on design parameters targeting the ECM.

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Polymer-Based Smart Drug Delivery Systems for Skin Application and Demonstration of Stimuli-Responsiveness

Polymers ◽

10.3390/polym13081285 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1285

Author(s):

Louise Van Gheluwe ◽

Igor Chourpa ◽

Coline Gaigne ◽

Emilie Munnier

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Ex Vivo ◽

Delivery Systems ◽

Stimuli Responsive ◽

Stimuli Responsive Polymers ◽

Smart Drug ◽

Smart Drug Delivery

Progress in recent years in the field of stimuli-responsive polymers, whose properties change depending on the intensity of a signal, permitted an increase in smart drug delivery systems (SDDS). SDDS have attracted the attention of the scientific community because they can help meet two current challenges of the pharmaceutical industry: targeted drug delivery and personalized medicine. Controlled release of the active ingredient can be achieved through various stimuli, among which are temperature, pH, redox potential or even enzymes. SDDS, hitherto explored mainly in oncology, are now developed in the fields of dermatology and cosmetics. They are mostly hydrogels or nanosystems, and the most-used stimuli are pH and temperature. This review offers an overview of polymer-based SDDS developed to trigger the release of active ingredients intended to treat skin conditions or pathologies. The methods used to attest to stimuli-responsiveness in vitro, ex vivo and in vivo are discussed.

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CHEMICAL MODIFICATION, CHARACTERIZATION AND EVALUATION OF MUCOADHESIVE POTENTIALITY OF ASSAM BORA RICE STARCH

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i9.20108 ◽

2017 ◽

Vol 9 (9) ◽

pp. 132 ◽

Cited By ~ 1

Author(s):

Abdul Baquee Ahmed ◽

Iman Bhaduri

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Sustained Release ◽

Chemical Modification ◽

Ex Vivo ◽

Rice Starch ◽

Modified Starch ◽

Native Starch ◽

Ft Ir

Objective: The objective of the present study was to chemical modification, characterization and evaluation of mucoadhesive potentiality of Assam bora rice starch as potential excipients in the sustained release drug delivery system. Methods: The starch was isolated from Assam bora rice and esterified using thioglycolic acid and characterized by Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC) and Nuclear magnetic resonance (NMR). The 10% w/v gel formulation based on modified bora rice starch loaded with irinotecan (0.6%) was prepared and evaluated for various rheological properties, ex-vivo mucoadhesion using goat intestine and in vitro drug release study in phosphate buffer pH 6.8.Results: The chemical modification was confirmed by FT-IR and NMR studies with the presence of the peak at 2626.74 cm-1 and a singlet at 2.51 respectively due to–SH group. Ex-vivo mucoadhesion studies showed 6.6 fold increases in mucoadhesion of the modified starch with compared to native starch (46.3±6.79g for native starch; 308.7±95.31g for modified starch). In vitro study showed 89.12±0.84 % of drug release after 6 h in phosphate buffer pH 6.8 and the release kinetics followed Non-Fickian diffusion.Conclusion: The modified Assam bora rice starch enhanced a mucoadhesive property of the native starch and thus, can be explored in future as a potential excipient for the sustained release mucoadhesive drug delivery system.

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Development of Piperine-Loaded Solid Self-Nanoemulsifying Drug Delivery System: Optimization, In-Vitro, Ex-Vivo, and In-Vivo Evaluation

Nanomaterials ◽

10.3390/nano11112920 ◽

2021 ◽

Vol 11 (11) ◽

pp. 2920

Author(s):

Ameeduzzafar Zafar ◽

Syed Sarim Imam ◽

Nabil K. Alruwaili ◽

Omar Awad Alsaidan ◽

Mohammed H. Elkomy ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Oral Delivery ◽

Ex Vivo ◽

In Vitro Release ◽

System Optimization ◽

Globule Size

Hypertension is a cardiovascular disease that needs long-term medication. Oral delivery is the most common route for the administration of drugs. The present research is to develop piperine self-nanoemulsifying drug delivery system (PE-SNEDDS) using glyceryl monolinoleate (GML), poloxamer 188, and transcutol HP as oil, surfactant, and co-surfactant, respectively. The formulation was optimized by three-factor, three-level Box-Behnken design. PE-SNEDDs were characterized for globule size, emulsification time, stability, in-vitro release, and ex-vivo intestinal permeation study. The optimized PE-SNEDDS (OF3) showed the globule size of 70.34 ± 3.27 nm, percentage transmittance of 99.02 ± 2.02%, and emulsification time of 53 ± 2 s Finally, the formulation OF3 was transformed into solid PE-SNEDDS (S-PE-SNEDDS) using avicel PH-101 as adsorbent. The reconstituted SOF3 showed a globule size of 73.56 ± 3.54 nm, PDI of 0.35 ± 0.03, and zeta potential of −28.12 ± 2.54 mV. SEM image exhibited the PE-SNEDDS completely adsorbed on avicel. Thermal analysis showed the drug was solubilized in oil, surfactant, and co-surfactant. S-PE-SNEDDS formulation showed a more significant (p < 0.05) release (97.87 ± 4.89% in 1 h) than pure PE (27.87 ± 2.65% in 1 h). It also exhibited better antimicrobial activity against S. aureus and P. aeruginosa and antioxidant activity as compared to PE dispersion. The in vivo activity in rats exhibited better (p < 0.05) antihypertensive activity as well as 4.92-fold higher relative bioavailability than pure PE dispersion. Finally, from the results it can be concluded that S-PE-SNEDDS might be a better approach for the oral delivery to improve the absorption and therapeutic activity.

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Multifunctional exosome-mimetics for targeted anti-glioblastoma therapy by manipulating protein corona

Journal of Nanobiotechnology ◽

10.1186/s12951-021-01153-3 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Jun-Yong Wu ◽

Yong-Jiang Li ◽

Jiemin Wang ◽

Xiong-Bin Hu ◽

Si Huang ◽

...

Keyword(s):

Drug Delivery ◽

Serum Proteins ◽

Protein Corona ◽

Significant Inhibition ◽

Brain Drug Delivery ◽

New Strategy ◽

Penetration Ability ◽

Tumor Drug Delivery ◽

Targeting Ability ◽

Tumor Area

AbstractTargeted drug delivery to the glioblastoma (GBM) overcoming blood–brain barrier (BBB) has been challenging. Exosomes are promising vehicles for brain tumor drug delivery, but the production and purification hinder its application for nanomedicine. Besides, the formation of protein corona (PC) may affect the behaviour of nanocarriers. Here, multifunctional exosomes-mimetics (EM) are developed and decorated with angiopep-2 (Ang) for enhancing GBM drug delivery by manipulating PC. Docetaxel (DTX)-loaded EM with Ang modification (DTX@Ang-EM) show less absorption of serum proteins and phagocytosis by macrophages. Ang-EM show enhanced BBB penetration ability and targeting ability to the GBM. Ang-EM-mediated delivery increase the concentration of DTX in the tumor area. The multifunctional DTX@Ang-EM exhibits significant inhibition effects on orthotopic GBM growth with reduced side effects of the chemotherapeutic. Findings from this study indicate that the developed DTX@Ang-EM provide a new strategy for targeted brain drug delivery and GBM therapy. Graphical abstract

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