Emerging Trends in Bilosomes as Therapeutic Drug Delivery Systems
Abstract
:1. Introduction
2. Methodology
3. Bilosomes: Structural Aspects
3.1. Lipids as a Component of Bilosomes
3.2. Non-Ionic Surfactant as a Component of Bilosomes
3.3. Bile Salts as a Component of Bilosomes
4. Bilosomes as Nanocarrier Drug Delivery System for Treating Various Disorders
4.1. Bilosomes as Drug Delivery System for Brain Disorders
4.2. Bilosomes as an Ocular Drug Delivery System
4.3. Bilosomes for Delivery of Oral Vaccines
4.4. Bilosomes for Delivery of Proteins and Peptides
4.5. Bilosomes as Transdermal Drug Delivery System
No. | Drug | Formulation | Therapeutic Problem | Study Outcomes | Ref. |
---|---|---|---|---|---|
1 | Diacerin (DCN) | Bilosomes | Poorly bioavailable (35–56%) osteoarthritic drug with gastrointestinal side effects on oral administration | Bilosomes were found to be superior than niosomes and pure suspension for enhancing DCN flow through the skin | [11] |
2 | Olmesartan medoxomil (OLM) | PEGylated bilosomes | Poor oral bioavailability of 26% which limits its therapeutic efficacy | Higher OLM deposition in rat’s skin from bilosomal formulation compared to transethosomes and OLM suspension was found as per in vivo skin deposition studies | [24] |
3 | Tizanidine HCL (TZN) | Bilosomes | Poor bioavailability | Enhanced transdermal permeation compared to plain drug | [64] |
4 | Terbutaline sulfate (TBN) | TBN chitosan-coated bilosomes (TBN-CTS-BLS) | Poor oral bioavailability due to hepatic first-pass metabolism | 2.33-fold increase in TBN bioavailability and t1/2 was increased to 6.21 ± 0.24 h when using the optimized TBN-CTS-BLS formulation compared to the oral TBN solution in the rat model | [65] |
5 | Lornoxicam | Bilosomes | Poor aqueous solubility and rapid clearance, GIT toxicity | In vivo pharmacodynamic activity in male rats and mice model demonstrated enhanced anti-inflammatory and antinociceptive activity compared to that of the oral marketed product | [66] |
6 | Dapsone (DPS) | Bilosomes | Low solubility and toxicity through oral administration | Ex vivo deposition study of optimized DPS-loaded bilosomes showed 170.57 ± 55.12 μg/mL DPS retention compared to 120.24 ± 10.7 μg/mL from DPS alcoholic solution | [68] |
7 | Sildenafil citrate (SC) | Nanobilosomes | Poor bioavailability | In vivo study in Sprague Dawley rats revealed 2-folds increase in intromission frequency and intromission ratio compared to untreated group | [69] |
8 | Teroconazole (TCZ) | Highly deformable bilosomes (HBs) | Poor permeability | In vivo studies showed improvement in terconazole skin deposition compared to typical bilosomal formulation and TCZ suspension | [70] |
9 | Diclofenac sodium (DNa) | Bilosomal gel | Gastrointestinal side effects on oral administration | Ex vivo permeation studies of optimized formulation showed a 2.5-fold increase in skin permeability than DNa solution, In vivo studies in paw edema rat model also revealed significant suppression of inflammatory mediators and reduction in paw edema | [71] |
10 | Metformin HCL | Bilosomes | Adverse effects | Permeation flux was found to be enhanced (198.79–431.91 ng cm −2 h−1) in comparison to the plain drug (154.26 ng cm −2 h−1). | [72] |
11 | Miconaole nitrate (MN) | Chitosan–carbopol bilosomal gel | Poor water solubility | Enhanced antifungal activity compared to pure drug against Candida albicans and Aspergillus niger | [73] |
12 | Simvastatin (SMV) | Bilosomal gel | Poor bioavailability due to water insolubility and hepatic first-pass effect. | 3-fold increase in SMV transdermal flux from SMV-loaded bilosomal gel compared to plain drug suspension. Bioavailability of SMV-BS gel was also found to be ~2-fold and ~3-fold higher than those of oral SMV suspension and SMV gel, respectively | [74] |
13 | Dronedarone hydrochloride (DRN) | Bilosomal nanogel | Poor bioavailability | Bilosomal gel demonstrated enhanced release (57.0 ± 8.68% of DRN compared to only 13.3 ± 1.2% released from drug suspension after 12 h) and enhanced skin permeation | [75] |
4.6. Bilosomes as Cancer Drug Delivery System
No. | Drug | Formulation | Therapeutic Problem | Study Outcomes | Ref. |
---|---|---|---|---|---|
1 | Cisplatin | Cytostatic bile acid incorporated liposomes | Cisplatin resistance in cancer cell lines | Enhanced ability of anticancer drug to be taken up by cancer cell due to the presence of cytostatic bile acids. | [77] |
2 | Silymarin | Dextrose-modified bilosomes | Poor bioavailability and low solubility | Dextrose bilosomes loaded with silymarin were tested in vivo for treating Diethyl nitrosamine (DEN)-induced hepatic malignancy. The mice had longer lifespans and less tumor load, suggesting more therapeutic potential. | [78] |
3 | Lead acrylamide molecules | Lead acrylamide molecules utilizing 4e-charged PEGylated bilosomes | Poor bioavailability and low solubility | Cytotoxicity testing showed that compounds 4e and 5d were effective against MCF-7 cells. After integration into the nano-PEGylated bilosomal system, the drug’s cytotoxic activity was increased. | [79] |
4 | Icariin and Melittin | Icariin-loaded bilosomes-melittin (ICA-BM) | Poor bioavailability and low solubility | ICA-BM showed a lower IC50 than blank-BM and ICA-pure. ICA-BM formulation increased icariin’s effectiveness against malignant pancreatic cells. | [80] |
5 | Luteolin | PEGylated bilosomes (LL-BLs) | Poor bioavailability and low solubility | LL-BLs showed greater cell viability than the pure drug on MDA-MB-231 and MCF-7 breast cancer cell lines. It was found that the IC50 values for MCF-7 and MDA-MB-231 cancer cells were 390 M and 510 M, respectively. | [82] |
6 | Sulfated polysaccharide–protein complexes | Bilosomes | Poor bioavailability and low solubility | Substantial decrease in serum α-fetoprotein, endoglin, lipocalin-2, and heat shock protein 70 levels. The photomicrographs of rat liver tissue slices showed a focal area of pleomorphic hepatocytes that had deteriorated, together with fine fibrosis emanating from the portal region. | [83] |
7 | Curcumin (CUR) analogue 3,5-bis(4-bromobenzylidene)-1-propanoylpiperidin-4-one | Nano-bilosomes | Poor bioavailability and permeability | Antitumor selectivity index of CUR analogue-loaded bilosomes recorded 420.55 against liver cancer cells when compared to a CUR suspension. | [85] |
8 | Apigenin | Chitosan-coated bilosomes | Poor bioavailability and low solubility | Antimicrobial and cell viability analyses demonstrated better outcomes with regard to inhibition and cell line assessment against two MCF-7 breast cancer and A549 lung cancer cell lines. | [87] |
9 | Pitvaststin | Bilosomes | Poor bioavailability | Improvement in the cytotoxicity of HepG2 spheroids, which was 44 times greater than that of pitavastatin (PIT) solution. | [88] |
10 | Quercetin | Chitosan-coated quercetin-bilosomes | Low bioavailability | 1.61-fold higher cytotoxicity of surface-modified chitosan-coated quercetin-bilosomes against MFC7 and 1.44-fold higher cytotoxicity against MDA-MB-231 than pure quercetin. | [89] |
11 | Psoralidin (Ps) | Chitosan-coated bilosomes | Water insoluble, dose-dependent toxicity | Apoptotic and necrotic potential of the developed formulation was evaluated in human breast cancer cell lines (MCF-7) and human lung adenocarcinoma cell lines (A549), in which a significant increase in the percentages of the apoptotic and necrotic cells was found compared to the control and free Ps. | [91] |
12 | Doxorubicin (DOX) | Bilosomes | High dose-related toxicity | Formulation showed improved DOX cytotoxicity against breast cancer cells (MCF-7) and the reduced IC50 value from 13.3 μM to 0.1 μM. A 4.5–6 and 1.8–2.5-fold increase in drug absorption from jejuno-ileum and colon was demonstrated. | [18] |
4.7. Bilosomes for Delivery of Herbal Drugs
No | Drug | Formulation | Therapeutic Problem | Outcome of Study | Ref. |
---|---|---|---|---|---|
1 | Silymarin | Bilosomes | Poor water solubility and stability | Ex vivo intestinal uptake study revealed the superiority of bilosomes compared to liposomes for strong hepatoprotective effect | [12] |
2 | Berberine (BER) and curcumin (CUR) | Bilosomes | Poor bioavailability and biodistribution | In vivo pharmacokinetic evaluation of bilosomal formulation in mice model showed improved and synchronized oral bioabsorption of both BER and CUR | [15] |
3 | Apigenin (AG) | Bilosomes | Poor bioavailability and low solubility | In vivo permeation and pharmacokinetic studies showed that the free AG-dispersion had a 4.49 times higher flux and a 4.67 folds higher AUC0–t | [95] |
4 | Piperine | Bilosomes | Poor bioavailability and low solubility | Piperine-loaded bilosomes had higher oral bioavailability than piperine suspension. Additionally, the optimized formula’s antiviral activity and safety margin were much higher than those of the drug suspension | [96] |
5 | Berberine (BER) | Chitosan-coated bilosomal gel | Poor bioavailability and low solubility | In comparison to the BER solution, formulation showed greater stability and sustained release of BER. In vivo study, formulation significantly reduced blood sugar, with a maximum drop of 41%, compared to BER-blood SOL’s sugar reduction of only 19% | [16] |
6 | Resveratrol (RSV) | Nanobilosomes | Poor bioavailability | Caco-2 cell lines study showed 4.7 fold increase in cellular uptake compared to RSV dispersion | [100] |
5. Conclusions and Future Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Kaurav, H.; Tripathi, M.; Kaur, S.D.; Bansal, A.; Kapoor, D.N.; Sheth, S. Emerging Trends in Bilosomes as Therapeutic Drug Delivery Systems. Pharmaceutics 2024, 16, 697. https://doi.org/10.3390/pharmaceutics16060697
Kaurav H, Tripathi M, Kaur SD, Bansal A, Kapoor DN, Sheth S. Emerging Trends in Bilosomes as Therapeutic Drug Delivery Systems. Pharmaceutics. 2024; 16(6):697. https://doi.org/10.3390/pharmaceutics16060697
Chicago/Turabian StyleKaurav, Hemlata, Meenakshi Tripathi, Simran Deep Kaur, Amit Bansal, Deepak N. Kapoor, and Sandeep Sheth. 2024. "Emerging Trends in Bilosomes as Therapeutic Drug Delivery Systems" Pharmaceutics 16, no. 6: 697. https://doi.org/10.3390/pharmaceutics16060697
APA StyleKaurav, H., Tripathi, M., Kaur, S. D., Bansal, A., Kapoor, D. N., & Sheth, S. (2024). Emerging Trends in Bilosomes as Therapeutic Drug Delivery Systems. Pharmaceutics, 16(6), 697. https://doi.org/10.3390/pharmaceutics16060697