Table 3 Pharmacokinetic study of invasomes

1.

Dragicevic-Curic et al. developed the temoporfin (hydrophobic drug) loaded invasomes using a ratio of limonene, citral, and cineole as a penetration enhancer and tested the in vitro permeation of temoporfin into abdominal human skin using Franz diffusion cells.

Invasomes containing 1% (w/v) cineole showed the highest skin penetration enhancement of temoporfin. Also, it gives exorbitant amounts of temoporfin the SC and deeper skin layers.

[15]

2.

Yet another study showed the temoporfin (hydrophobic drug) invasomes efficacy for topical application onto the skin of mice bearing the subcutaneously implanted human colorectal tumor HT29.

The results showed a benefit above the previously reported delivery of temoporfin systems for delivering anticancer drugs more efficiently to the subcutaneous layer of skin.

[33]

3.

In this study, isotretinoin-loaded invasomal gel was developed to achieve targeted delivery of drugs to the pilosebaceous follicular unit.

The developed gel formulation exhibited a biphasic ex vivo permeation behavior (fast permeation and zero-order) and after 2 h the permeation slowed down without altering the order of permeation. Also, it showed the penetration of invasomes to the deep dermal region of the skin for pilosebaceous targeting.

[27]

4.

Chen et al. accomplished ferulic acid-loaded invasomes for efficient delivery to the targeted skin part and compared with other vesicular systems.

Tween 80-based invasomes showed improved permeation profiles and enhanced skin deposition of ferulic acid.

[42]

5.

In 2013, Prasanthi et al. developed the finasteride-loaded invasomal vesicle for transdermal delivery using the iontophoretic technique.

The optimized invasomal formulation enhanced permeation rate, flux, bioavailability, and half-life using the iontophoretic technique.

[30]

6.

Kamran et al. reported the olmesartan-loaded novel nano-invasome using b-citronellene as a permeation enhancer to increases the bioavailability and biological half-life of a drug.

The confocal laser microscopy of rat skin revealed the drug was eventually distributed and permeated deep into the skin. It showed 1.15 times improvement in bioavailability concerning the control olmesartan formulation in Wistar rats.

[40]

7.

In 2014, Lakshmi et al. developed the curcumin-loaded cyclodextrin and hydroxypropyl β-cyclodextrin complex and incorporated it into invasome and then formulate the hydroxypropyl cellulose gel as a transdermal formulation and observed for ex vivo skin permeation studies using rat abdominal skin.

Invasomal preparation exhibited an enhanced permeation rate (8.11 times) as compared with the control. In vivo diffusion studies showed the high cumulative drug permeation rate, steady-state transdermal flux as compared with the control formulation.

[43]

8.

In 2018, El-Nabarawi et al. investigated the dapsone-loaded invasome using unique types of terpene through thin-film hydration and tested for the ability to in vivo delivery of the dapsone through the skin using Wistar rats.

The in vivo skin deposition amount of dapsone was increased (4.11 mcg/cm2) as compared with alcoholic drug solution (1.71 μg/cm2). Interestingly AUC of dapsone-loaded invasomes was nearly 2-fold greater than dapsone solution

[36]

9.

In this study, the nanosized avanafil-loaded invasomes is used to increase the transdermal delivery of drug and consequently bioavailability of avanafil.

The results of the invasomal film showed enhanced ex vivo permeation with an enhancement factor of 2.514. Also, a 4-fold increase in relative bioavailability compared with the raw avanafil film.

[39]

10.

Tolterodine tartrate–loaded invasomes were prepared using different terpene, soya lecithin, ethanol, and tested for transdermal penetrations.

The iontophoretic drug transport showed that the permeability of tolterodine tartrate released from invasomes was higher compared with that of free drug proving the additive effect of invasomes and iontophoresis. Also, invasome formulation containing limonene showed high penetration because of its lipophilicity and low boiling point.

[12, 41]

11.

In 2017, Qadri et al. developed the isradipine-loaded invasome using Phospholipon® 90G, b-citronellene (terpene), and ethanol by conventional thin-layer evaporation technique and tested transdermal flux, bioavailability, etc.

It showed an enhanced permeation of isradipine invasomes to the deeper layers of the rat skin. It was found more effective, and it reduces the 20% blood pressure by improved permeation through Wistar rat skin.

[26]

12.

Ultra-flexible invasomes for transdermal delivery of capsaicin loaded has been designed using Comperlan® KD and d-limonene as a potential penetration enhancer.

The skin permeation study showed that invasomes exhibited significantly higher permeation as compared with the conventional liposomes and 0.15% capsaicin in ethanolic solution (commercial product).

[37]

13.

The phenylethyl resorcinol-loaded invasomes have been designed by Amnuaikit et al. for topical delivery of phenyl ethyl resorcinol.

It showed efficiency to deliver phenylethyl resorcinol into the deep skin in both quantity and effectiveness.

[38]

14.

Anastrozole was loaded into invasomes and formulate the invasomal gel using sodium carboxymethyl cellulose for effective transdermal delivery of the anticancer drug in the treatment of breast cancer.

Ex vivo permeation study showed an enhancement of transdermal flux and the skin deposition of the drug (73%) have been studied on male Wistar rat skin. Also, prepared invasomal gel showed first-order kinetics behavior with Higuchi model-dependent kinetics.

[34]

15.

The hydrophilic model drug-loaded invasomal formulations have been designed and tested for skin permeation and penetration using microneedles based device (Dermaroller®) with different needle lengths.

Interestingly, it has been observed the skin perforation with the Dermarollers® enhanced drug (carboxyfluorescein and mannitol) penetration and permeation for both developed invasomal formulations as compared with aqueous drug solutions.

[32]

16.

Verma et al. developed the lipophilic drug (cyclosporine A) loaded invasomes to enhance the penetration of cyclosporine A.

Interestingly, it revealed an in vitro study on human skin, the invasomes provided a significantly higher amount of cyclosporine A in the deeper layers of human skin (feasible epidermis and dermis).

[12]

17.

Shah et al. developed and compared the ability of drug-loaded vesicular systems (cationic LeciPlex, invasomes, and conventional liposome) to deliver the drugs deep into the skin.

The ex vivo study showed the invasomes increased the delivery of azelaic acid at the site of inflammation of acne as compared with other vesicular systems, which resulted in the fast therapeutic action.

[25]

18.

In 2009, Mura and co-authors developed the minoxidil-loaded invasomes using soya lecithin, and different penetration enhancer to achieve efficient (trans) dermal delivery.

In vitro diffusion through newborn pig skin showed the developed invasomes achieved the significant improvement of minoxidil deposition in the skin and consequently improving cutaneous drug bioavailability.

[35]