Table 1.
Brief presentation of lipid-based formulations investigated for encapsulation and delivery of anti-TB drugs.
| Vehicles | Composition | Drug Molecules | System Specificity and Functionality | Reference |
|---|---|---|---|---|
| Liposomes | Phosphatidylcholine, cholesterol | Isoniazid, pyrazinamide, rifampicin, ethionamide, streptomycin | Attempt for multiple drug encapsulation in liposomes; co-encapsulation of isoniazid and pyrazinamide was successful whereas rifampicin, ethionamide, and streptomycin was not substantial | [72] |
| Egg phosphatidylcholine, cholesterol, maleylated bovine serum albumin, O-steroyl amylopectin/dicetylphosphate | Rifampicin | Enhanced drug concentration in alveolar macrophages, a higher clearance rate of M. smegmatis in the rat macrophage, improved efficiency with aerosol formulation | [73] | |
| Phosphatidylcholine, cholesterol | Rifampicin Isoniazid |
Sustained drug release in alveolar macrophages by pulmonary administration to guinea pigs | [74] | |
| Egg yolk phosphatidylcholine type XI-E, dipalmitoylphosphatidylcholine, cholesterol | Rifampicin Isoniazid |
Co-loading increased the encapsulation and extended the release of both drugs | [75] | |
| Dipalmitoyl phosphatidylcholine (DPPC) | Isoniazid | Deep lung deposition (27%), effective delivery of isoniazid, lung surfactant mimic action | [76] | |
| Soybean phosphatidylcholine, cholesterol, mannitol | Isoniazid | Proliposomes with attractive flowability, powder performance, and promising biological effect | [77] | |
| Soy phosphatidylcholine/hydrogenated derivative, cholesterol, oleic acid | Rifampicin | Good cellular uptake and less toxicity towards alveolar epithelium for the formulation without oleic acid | [78] | |
| Hydrogenated soy phosphatidylcholine, cholesterol | Rifampetine | Antimicrobial efficacy without cytotoxicity in A549 cells | [79] | |
| Phospholipid (Lipoid S-75), sulfphobutyl ether P-cyclodextrin, vitamin C | Rifampicin | Good flowability, aerodynamic diameter for pulmonary delivery, good in vitro antitubercular activity | [80] | |
| Soy lecithin, cholesterol | Rifampicin | Controlled and sustained release behavior, better pharmacokinetic profile | [81] | |
| 4-aminophenyl-a-D mannopyranoside as a macrophage-targeting agent. Cholesteryl hemisuccinate (CHEMS) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) | Isoniazid Ciprofloxacin |
pH stimuli release optimal at macrophage acidic conditions, high alveolar macrophage uptake, and pulmonary delivery of drug achieved | [82] | |
| Hydrogenated phosphatidylcholine from soybean, cholesterol, α-tocopherol, and folate-MPEG2000-DSPE | Rifampicin Ofloxacin |
Efficient antimicrobial activity in vitro and in murine models, enhanced pharmacokinetic profiles, macrophage-targeting activity, and particulates endowed with radiolabeling properties for visualization | [83] | |
| D-erythro-sphingosine-1-phosphate (S1P); lysobisphosphatidic acid (LBPA) or arachidonic acid, L-α-phosphatidylserine | Phosphatidic acid Phosphatidylinositol 3-phosphate Phosphatidylinositol 5-phosphate |
Increased intracellular death of Mycobacteria BCG and Pseudomonas aeruginosa by phagosome acidification and ROS generation | [84] | |
| Crude soybean lecithin and cholesterol | Isoniazid | Crude soybean lecithin liposomes exhibited much higher encapsulation efficiency for isoniazid than purified soybean lecithin liposomes, introducing the crude product for cost-effective drug encapsulation | [85] | |
| Dimethyldioctadecylammonium (DDA), monophosphoryl lipid A (MPLA), trehalose 6,6′-dibehenate (TDB) | DNA vaccine | Slow and prolonged release of DNA, enhanced and persistent protection against TB, increased storage stability of the vaccine | [86] | |
| Crude soybean lecithin and cholesterol | Isonicotinic acid (4-hydroxy-benzylidene)-hydrazide | Crude soybean lecithin liposomes showed high encapsulation efficiency for hydrazone–drug conjugates and controlled release of isoniazid at different pH | [87] | |
| Crude soybean lecithin | Isoniazid-grafted zinc phthalocyanine | The conjugation of chemotherapeutics to phthalocyanines as a potential strategy for liposomal controlled release was successfully established | [87] | |
| Dipalmitoylphosphatidylcholine, cholesterol | Zinc phthalocyanine | Inactivation of sensible and multidrug-resistant strains of M. tuberculosis by photodynamic activity | [88] | |
| Crude soybean lecithin | Inclusion complexes of cyclodextrin with isoniazid-grafted zinc phthalocyanine | The use of cyclodextrin complexation to facilitate liposomal encapsulation of hydrophobic compounds under organic, solvent-free conditions was introduced | [9] | |
| Crude soybean lecithin | Rifampicin Isoniazid |
The feasibility of using crude soybean lecithin for preparation of combination products for liposomal dual delivery was demonstrated | [89] | |
| Crude soybean lecithin | Rifampicin and isoniazid-grafted zinc phthalocyanine |
The prepared liposomes demonstrated pH-dependent controlled dual delivery of the two drugs, good biocompatibility, and marked uptake by the lung fibroblasts and epithelial cells | [90] | |
| Niosomes | Span® 85, cholesterol | Rifampicin | Good distribution with lung affinity of approximately 65% due to the controlled size of particles | [91] |
| Span® 60, cholesterol | Isoniazid | Low accumulation of drugs in visceral organs (lung, kidney, spleen) | [92] | |
| Span® 60/85, cholesterol, dicetyl phosphate/stearyl amine | Pyrazinamide | Improved drug efficacy in guinea pigs infected with M. tuberculosis | [93] | |
| Span® 20/60, cholesterol, di-cetylphosphate | Isoniazid | Prolonged delivery in treated sites and high macrophage uptake of negatively charged particles | [94] | |
| Triton X 100, polyethylene glycol (PEG) 2000, Span® 80 | Rifampicin Isoniazid Pyrazinamide |
Stability and compatibility of drugs in niosomes, release of rifampicin and isoniazid by a Fickian mechanism, and a non-Fickian release observed for pyrazinamide | [95] | |
| Tyloxapol, PEG 2000 | Rifampicin Isoniazid Pyrazinamide |
Stability of the formulation, isoniazid released by a Fickian diffusion, rifampicin and pyrazinamide by a non-Fickian mechanism | [96] | |
| Span® 60/85, cholesterol, dicetyl phosphate/stearyl amine | Ethambutol | Good stability for neutral and positively charged niosomes | [97] | |
| Solid lipid nanoparticles | Stearic acid | Rifampicin Isoniazid Pyrazinamide |
Good aerodynamic size for broncho-alveolar delivery, bioavailability, greater activity in M. tuberculosis infected guinea pigs, and no hepatotoxicity induced | [98] |
| Cetyl palmitate, Tween® 80/Poloxamer 188 | Rifampin | Improved antitubercular activity and sustained release of rifampin | [99] | |
| Stearic acid, sodium taurocholate | Rifampicin | Appropriate aerodynamic size for pulmonary delivery to alveolar epithelium, with good respirability fraction (>50%) and activity against Bacillus subtilis strains | [100,101] | |
| Glyceryl dibehenate/glyceryl tristearate, Tween® 80 | Rifabutin | The macrophage uptake of 46% for nanoparticles made with glyceryl dibehenate and low cytotoxicity effect on lung cell lines | [102] | |
| Cetyl palmitate, chitosan | Rifampicin | Higher in vitro mucoadhesive properties and permeability in alveolar epithelial cells | [103] | |
| Comptitol, Tween ® 80 |
Ethambutol | Biocompatible, non-toxic particles, dry powder inhaler suitable for pulmonary delivery | [104] | |
| Nanostructured lipid carriers | Polyoxyethylene 40 stearate, caprylic/capric triglyceride, and polyoxyl 40 hydrogenated castor oil, Poloxamer 407, cetyltrimethylammonium bromide | Rifampicin | Improved uptake of drug in alveolar macrophages | [105] |
| Precirol®ATO 5, polysorbate 60, miglyol-812, mannose | Rifampicin | Efficient uptake by bone-marrow-derived macrophages and decrease in the intracellular growth of the mycobacteria | [57] | |
| Lipoid S-75, Tween 80, Poloxamer 188, Precirol® ATO-5, glyceryl distearate, squalene |
Rifampicin | Enhancement of pharmacokinetic parameters and improvement of drug bioavailability | [106] | |
| Emulsions | Oleic acid, phosphate buffer, Tween 80, ethanol | Rifampicin | Controlled release of rifampicin achieved | [107] |
| Oleic acid, phosphate buffer, Tween 80, ethanol | Isoniazid | Stable formulation, isoniazid release by a non-Fickian release mechanism | [107] | |
| Ethyl oleate, Brij 96, Butanol | Rifampicin Isoniazid Pyrazinamide |
Isoniazid and rifampicin located at the interface toward oil side, pyrazinamide remained in free water Isoniazid and pyrazinamide released by Fickian mechanism and rifampicin exhibited anomalous release |
[108,109] | |
| Capmul MCM C8, Labrasol, Cremophor-EL | Rifampicin | Intestinal permeation of rifampicin facilitated, improved pharmacokinetic profile | [110] |