Editorial Feature

Bioactive-Loaded Nanotechnology Applications for Drug Discovery

A variety of naturally occurring bioactive plants for the treatment of many diseases exist, and these plants have been widely used for millennia around the world due to their small side effects and significant health benefits.

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Plants have been used for medicine and nourishment since the dawn of society. Despite the various benefits, pharmaceutical companies are often hesitant to fund natural product-based drug development and instead focus on the synthetic compound library for innovative drug development.

Natural products and phytoconstituents, on the other hand, have been extracted and screened for their advantages in basic health issues such as diabetes, cancer, microbial diseases, heart disease, and inflammatory conditions due to their unique benefits—which include reduced toxicity, low cost, fewer side effects, and superior health benefits.

Plant-based medicines have some drawbacks, such as low lipid solubility, instability, and the need for a well-validated method for ingredient extraction and purification. Furthermore, manufacturers must overcome these restrictions and ensure that the product is stable enough for patients to consume safely.

Newer improved drug delivery systems (DDS) for plant-based therapies have been designed to eliminate these constraints. Liposomes, phytosomes, ethosomes, transferosomes, nanostructured lipid carriers (NLCs), cubosomes, solid lipid nanoparticles (SLNs), hexosomes, microspheres, nanoparticles, and nanoemulsions are all examples of these.

Medicinal regulators have recently approved the first nanoparticle-based compositions containing lipid systems such as liposomes and micelles. Inorganic nanoparticles, such as magnetic and gold nanoparticles, were present in both formulations.

The physicochemical features of drug molecules determine the selection of nano-based formulations for drug administration at a specific place. Nanoscience has been increasingly popular in recent years for incorporating natural bioactives into nanoparticles.

The majority of the materials utilized are environmentally benign, biodegradable, bioadhesive, and of natural origin, providing a wide range of benefits as well as a unique size for the nano-formulations.

The biochemical and biophysical features of target drugs have largely determined the usage of a suitable medication and nano-DDS. Nonetheless, some drawbacks, such as toxicity, could not be overlooked in light of the advantages. The lack of knowledge about the toxicity and harmfulness of nanostructures is the primary source of concern, and more extensive investigations are unquestionably required to determine their maximal safety performance.

The current review paper published in the journal Pharmaceutics aims to describe natural products based on nano-DDSs, the widespread use of natural nanomedicines in various diseases, and various preparation techniques.

Discussion

Nanoscale materials have been created due to technological advancements over the last two decades, resulting in smaller particle sizes and larger surface areas. Nanoparticles are tiny particles that range in size from 1 to 1000 nm. The term “nano” is simple to define, yet it covers a variety of applications (Figure 1), including several nano-based systems comprised of diverse types of nanocarriers (Figure 2).

Applications of nanomedicines

Figure 1. Applications of nanomedicines. Image Credit: Kumari, et al., 2022

Illustrating various types of nano-formulations

Figure 2. Illustrating various types of nano-formulations. Image Credit: Kumari, et al., 2022

The SLN colloidal medication system, which has particle sizes ranging from 50 to 1000 nm, was developed in the early 1990s. These are emulsifiers that aid in the water stability of a melted solid lipid dispersion. Many processes have been proposed for the manufacture of SLNs (Figure 3), the most common of which being high-pressure homogenization (HPH) and micro-emulsification.

Another study found that “triptolide-loaded SLN” diminished myeloperoxidase (MPO) and glutathione (GSH) activities and functioned as an anti-inflammatory and antioxidant product, resulting in better solubility, reduced toxicity, and lowered GI irritation, as well as ignoring higher local drug concentration and gradual release of drugs. Table 1 contains more examples.

Methods of preparation of solid lipid nanoparticles (SLNs).

Figure 3. Methods of preparation of solid lipid nanoparticles (SLNs). Image Credit: Kumari, et al., 2022

Table 1. SLN encapsulating natural bioactive. Source: Kumari, et al., 2022

SLNs Loaded with Natural Bioactive Plant Source Limitations of
Free Drugs		 Advantages of Loaded Drug Molecules References
Triptolide incorporated SLN Tripterygium wilfordii Hook F Poor water solubility and high toxicity, Improved solubility, hyperemia, reduced toxicity, irritation to GIT, etc. [33]
Puerarin-loaded
SLN		 Pueraria lobata (wild) Howe Poor water solubility and low oral bioavailability 3-folds increase in absorption and bioavailability improved tissue concentration in targeted organs (heart and brain) [31,32]
Noscapine PEG conjugated SLN Papaveraceae family Shorter half-life, less efficacy to glioblastoma cells Improved biological half-life, and anticancer efficacy in glioblastoma in vitro and in Swiss male albino mice induced with brain cancer. [34]
Tetrandrine-loaded SLN Stephania tetrandra 
S. Moore		 Lesser bioavailability and drug release Improved bioavailability, in vitro drug release, cellular uptake into human lens epithelial cell line (SRA 01/04) [35]
Cantharidin-loaded SLN Mylabris phalerata pallas or mylabris cicchorii linnaeus Lesser bioavailability and drug release Sustained drug release without a burst effect, improved bioavailability when administered orally in rats induced with gastric mucus membrane irritation. [36]
Hydroxycitric acid-loaded SLN Garcinia
cambogia		 Low bioavailability Increased bioavailability tested on Wistar rat, anti-obesity medication [37]
Ginkgo biloba leaf extract-loaded SLN Ginkgo
biloba		 Low bioavailability Improved oral bioavailability at a 5 mg/kg dose, causing blood coagulation at higher doses i.e., 50 mg/kg. [38]
Aloe vera-loaded SLNs Aloe vera Cause irritation to the skin on multiple uses in some cases Incorporated into sunscreen cream, SPF was found to be as per the marketed formulation. [39]
Zataria multiflora essential oil (ZMEO) containing SLN Zataria
multiflora		 Mosquito repellant properties at higher doses Improved mosquito repellent activities, three times increase in protection time of nano-formulation compared to non-formulated essential oil [40]
Witepsol-loaded SLNs Cocoa butter Lower
stability		 Suitable vehicle for herbal extracts, higher stability, and proper release profile in the intestine. [41]

 

Due to their improved regulated drug release, improved drug loading capability, stability, and low drug loss after encapsulation, NLCs beat SLNs.

Several studies looked at the method to entrap bioactives in NLC by changing water solubilities, managing drug release, extending circulation time, co-delivery, drug delivery methods, and improving gastrointestinal absorption and oral bioavailability. In Figure 4, different techniques for preparing NLCs are listed.

Methods of preparation of nanostructured lipid carriers (NLCs).

Figure 4. Methods of preparation of nanostructured lipid carriers (NLCs). Image Credit: Kumari, et al., 2022

Table 2. NLCs incorporated bioactives. Source: Kumari, et al., 2022

Drug-Loaded NLCs Plant Source Limitations of Free Drugs Advantages of Loaded Drug Molecules over Conventional Systems Reference
Cardamom essential oil-loaded NLCs Elettaria
cardamom		 Low antimicrobial activities Protect antimicrobial activity of the plant extract, used as food supplement [46]
Thymoquinone-loaded NLCs Nigella
sativa		 Low bioavailability Enhanced bioavailability and oral drug delivery, antioxidant potential, improved liver biomarkers affected with PCM induced hepatotoxicity [47]
Citral-loaded
NLCs		 Cymbopogon citratus Low
solubility		 Improved water solubility and sustained drug release [48]
β-Elemene incorporated NLCs Nigella damascena L. Low bioavailability and anticancer efficacy Improved bioavailability in male wistar rats and anti-tumor efficacy in H22 hepatoma induced in Kunming mice, reduced venous irritation after i.v., injection in New Zealand white rabbits. [49]
Zerumbone-loaded NLCs Zingiber zerumbet
 L. Smith		 Low
solubility		 Improved water solubility, bioavailability, and sustained drug release with enhanced anticancer activities both in vitro and in vivo. [50,51]
Baicalin-loaded NLCs Scutellaria baicalensis Low solubility and bioavailability Improved sustained drug release and antidiabetic effect of baicalin [52]
Berberine incorporated NLCs Coptis
chinensis		 Low bioavailability Enhanced anti-inflammatory potential of the berberine, improved ulcerative colitis symptoms. [53]
Curcumin-loaded NLCs Curcuma
longa		 Low solubility and bioavailability Improving impressions of DR5 proteins, enhanced caspase 8 and caspase 3 activities, enhanced apoptosis in hepatocellular carcinoma [54]
Hesperidin and clarithromycin-loaded NLCs Flavanone
glycoside		 Low bioavailability Improved sustained and controlled drug release that can be used to increase the rate of H. pylori eradication. [55]
Diosgenin and Glycyrrhiza glabra extract-loaded NLCs Dioscorea deltoideaGlycyrrhiza glabra Possessed lessened anti-inflammatory properties Inhibition of pro-inflammatory cytokines, TNF-α, IL, and enhanced anti-inflammatory properties [56]
Cinnamaldehyde-loaded (NLC) Cinnamomum ceylanicum Low bioavailability and shelf life Total bacteria and fungi count in the treated CA-loaded NLC samples was about 3.5 log CFU/g less than the control. CA-loaded NLC can extend the shelf life of date fruit without any undesirable impacts on sensory attributes. [57]
Ursolic acid-loaded NLCs Pentacyclic terpene acid Low
solubility		 Animals infected with Leishmania (Leishmania) infantum and treated with UA-NLC showed lower parasitism than the infected controls, Increased protective immune response, spleen and liver preservation, and the normalization of hepatic and renal functions. [58]
Naringenin (NGN) incorporated NLCs Citrus fruits and tomato Poor water solubility Elevated drug release rate in simulated intestinal solutions in vitro, improved transepithelial transport in MDCK cells, improved oral absorption in mice, enhanced inhibitory effects of NGN on MCD diet-induced mouse NAFLD. [59]

 

Two approaches for producing nanocrystals have been established: a top-down approach and a bottom-up approach. Precipitation, high gravity-controlled precipitation technology, sono-crystallization, limited impinging liquid jet precipitation method, and multi-inlet vortex mixing procedures are all examples of top-down procedures (Figure 5).

The bottom-up technique, on the other hand, incorporates the use of high-pressure homogenization in grinding activities.

The polymer’s swelling and mucoadhesion properties allowed for continuous drug release, resulting in improved inhalation efficacy. Table 3 contains other examples.

Methods of preparation of nanocrystal

Figure 5. Methods of preparation of nanocrystal. Image Credit: Kumari, et al., 2022

Table 3. NLCs incorporated bioactives. Source: Kumari, et al., 2022

Nanocrystals of
Herbal Compounds		 Plant Source Limitations of Free Drugs Results and Outcomes of Loaded Formulations References
Rutin incorporated
nanocrystals (RNs)		 Buckwheat, eucalyptus Poor water solubility Improved water solubility and bioavailability, RNs showed 100 times more cytotoxic effect on HN5 cells, decreased expressions of Bcl-2 mRNA [64]
Cellulose nanocrystals isolated from Amla pomace Phyllanthus emblica Free drugs do not possess this property Cellulose nanocrystals help in converting food industry waste into valuable products, and act as a low-cost precursor for various nanoformulations [65]
Curcumin (CUR) and beclomethasone dipropionate (BDP) nanocrystals Curcuma longa Poor water solubility and bioavailability Improved water solubility and bioavailability, therapeutic efficacy, improved lung delivery of active molecule, improved asthmatic conditions [66]
Silymarin nanocrystals Silybum Marianum Low
solubility		 Improved drug dissolution profile, sustained drug release [67]
Ethanol extract from Ficus glomerata nanocrystals Ficus glomerata Lesser biological properties Showed comparable activities against Aedes aegypti, Culex quinquefasciatus, and Anopheles stephensi to the conventional neem oil-based nanoemulsion and repellent properties are more effective than commercial formulation. [68]
Puerarin Pueraria lobata Low bioavailability Enhanced oral bioavailability and upgraded brain accumulation for the treatment of Parkinson’s disease (PD) [69]
Resveratrol
nanocrystals		 Natural polyphenol Low water solubility Improved water solubility and dermal patches preparation for treatments of acne and skin diseases [70]

 

Nano-emulsions (NE) are non-homogeneous, transparent colloidal dispersion systems with a size of 100 nm that are both optically and thermodynamically stable. These are made up of water and oil, with co-surfactant and surfactant added later.

Figure 6 depicts various NE preparation methods as well as the structure of nanoemulsions. These are concentrated in the lymphatic system, supplied through intramuscular and subcutaneous routes, due to their increased interior membrane permeability.

More illustrations of NE application scenarios are shown in Table 4.

Methods of preparation of nanocrystal.

Figure 6. Methods of preparation of nanocrystal. Image Credit: Kumari, et al., 2022

Table 4. NLCs incorporated bioactives. Source: Kumari, et al., 2022

Herbal Nano-Emulsion Plant
Source		 Limitations of
Free Drugs		 Results and Outcomes of
Loaded Bioactive		 References
Hydroxy-safflor yellow A NE  Carthamus tinctorius Low absorption and bioavailability Enhanced systemic absorption and improved bioavailability. [77]
Oregano oil NE Origanum
vulgare		 Limited spectrum antibiotics Reduced and controlled growth of food-borne bacteria (L. monocytogenes, S. Typhimurium, and E. coli) on fresh lettuce. [71]
Elemene oil NE Curcuma
 species		 Low stability and bioavailability Improved stability and oral bioavailability in Sprague Dawley rats than a commercial elemene emulsion. [78]
Quercetin NE Many plant parts like nuts Low skin penetration cause skin irritation Increased cutaneous permeability reached the systemic circulation with lower skin retention. [79]
Basil oil NE Ocimum
basilicum		 Have lesser antibacterial activity Antibacterial activity against pure E. coli culture [80]
Nigella sativa L. NE Nigella
sativa L.		 Limited free radicle scavenging activity Enhanced and dose-dependent radical scavenging capacity in the DPPH assay (IC50 of about 47 µg/mL), reduced bioavailability of A2780 cancerous cells, NE showed pro-apoptotic, antioxidant, and anticancer effects. [81]
Linseed oil NE Linum usitatissimum
 seed		 Poorer stability and penetration through the skin membrane Improved stability and physicochemical properties for topical applications, suitable for atopic dermatitis evaluated through in vitro and in silico studies. [82]
Cumin tincture-loaded NE Cuminum
cyminum L.		 Limited free radicle scavenging activity and antibacterial properties Good and dose-dependent radical scavenging capacity, antioxidant, anti-angiogenic effect, antibacterial activity against S. aureus and K. pneumonia. [83]
Essential oil NE Alhagi
maurorum		 Limited bioavailability Enhanced antibacterial and antibiofilm activity, identified as antimicrobial agents against antibiotic-resistant bacteria. [84]
Nelumbo nucifera crude extracts. Nelumbo
nucifera		 Poorer
stability		 Enhanced stability and antimicrobial activities act as an alternative active ingredient for skin bacterial infection. [85]
Peppermint and rosemary essential oils NE Mentha piperita, Mint family Lamiaceae Dermal irritation and toxicity Reduced osteoarthritis pain via increasing antioxidant capacity and improving the histopathological features of the rats’ knee joint. [86]
Essential oil NE Thymus
vulgaris		 Limited antifungal properties Obtained as promising alternatives for the treatment of cutaneous mycoses, especially when the etiological agents are resistant to conventional antifungal drugs. [87]
Essential oil NE Myristica fragrans or Lavandula dentata Poorer
stability		 Improved physical and chemical stability in different temperature and storage conditions [88]

 

Due to its exceptional attribute of possessing phospholipid bilayers, liposomes can boost drug solubility, drug delivery, the bioavailability of the entrapped drug, uptake of the drug inside a cell, and drug distribution all through the body both in vivo and in vitro. Figure 7 shows the structure of liposomes as well as various liposome production methods.

The structure of liposomes and different methods of preparation of liposomes.

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Figure 7. The structure of liposomes and different methods of preparation of liposomes. Image Credit: Kumari, et al., 2022

To develop vaccines, nutraceuticals, and cosmetics, the ADME profiles of medications such as herbs, enzymes, and proteins can be adjusted suitably. Furthermore, unique characteristics such as environmental preservation of the entrapped drug molecule, severe primary destruction of loaded bioactive, cost-effectiveness, and fast therapy with minimal systemic morbidity boosted their utilization in bio-medicine formulations.

More herbal substances encapsulated in liposomes can be found in Table 5.

Table 5. Liposomes containing herbal bioactives. Source: Kumari, et al., 2022

Liposomes of Herbal Compounds Plant
Source		 Limitations of Free Drugs Results Reference
Baicalin-loaded
liposomes		 Root of Scutellaria baicalensis Georgi) Low water solubility and drug release Improved solubility, sustained release, enhanced drug concentration in brain tissue after i.v. administration in rats [95]
Polydatin-loaded
liposomes		 Root and rhizome of Polygonum cuspidatum Sieb Poorer solubility and bioavailability Enhanced oral bioavailability, improved solubility, and sustained release in vitro. [96]
Paclitaxel-loaded/PEGylated/
saturated PC-
based liposomes		 The bark of Taxus brevifolia or pacific yew Low solubility and bioavailability Improved bioavailability, solubility, biodistribution, and intracellular uptake. [97,98]
Naringenin-loaded
liposomes		 Immature orange fruit and the peels of grapefruits) Poorer solubility and bioavailability Improved stability, solubility, bioavailability, and tissue distribution the sustained release both in vivo and in vitro after oral administration. [99]
Sterols-loaded
liposomes		 Flammulina
velutipes		 Limited solubility and bioavailability Improved water solubility, oral bioavailability, and tissue distribution in liver tumor-bearing Kunming mice. [100]
Quercetin-loaded
liposomes		 Flavonoids Reduced solubility and bioavailability Improved water solubility, and oral bioavailability, used in wound healing [101]
Curcumin-loaded
liposomes		 Curcuma longa Low anticancer properties Anticancer and anti-inflammatory potential [102]
Curcumin-loaded
thiolated polymer-
coated liposomes		 Curcuma longa Low bioavailability The improved therapeutic index of curcumin, Aphthous ulcer [103]
Colchicine-loaded liposomes Colchicum autumnal, gloriosa superba extract Poorer drug release The anti-gout drug, improved drug transport [104]
Liposomal neem gel Azadirachta indica leaves Limited antibacterial spectrum Enhanced anti-bacterial activities [105]
Capsaicin liposomes Genus capsicum Low bioavailability Enhanced bioavailability, treating neuropathic pain [106]
Brucine liposomes Nux vomica Low bioavailability and showed side effects Reduced side effects of brucine like violent seizures [107]
Guggul liposomes Commiphora
Mukul.		 Low bioavailability Improved anti-inflammatory properties. [108]
Asparagus racemosus liposomes Asparagus racemosus Low bioavailability Improved anti-inflammatory properties. [109]
Polygonum aviculare L. herba (PAH) extract entrapped liposomes quercetin-entrapped liposomes Polygonum aviculare 
L.Quercetin		 Low cell viability Moderately efficient on cell viability while quercetin-loaded liposomes showed increased cell viability and provide better endothelial protection compared to free quercetin and PAH-loaded liposomes [110]

 

Phytosomes are lipid-compatible molecular aggregates that encase pharmacologically active and water-soluble phytochemicals in phospholipids, increasing solubility and bioavailability. Due to their large molecular size, hydrophilic phytochemicals like polyphenols and flavonoids have reduced absorption in the body, making absorption through biological membranes challenging. Phytosomes have helped to overcome these limitations.

The active material in liposomes is dissolved in the medium contained in the membrane layers, but the active material in phytosomes is an integral part of the membrane (Figure 8).

The structure of phytosomes and different methods of the preparation of liposomes.

Figure 8. The structure of phytosomes and different methods of the preparation of liposomes. Image Credit: Kumari, et al., 2022

Table 6. Phytosomes containing herbal medicines. Source: Kumari, et al., 2022

Phytosome Plant
Source		 Limitations of Free Drugs Results and
Outcomes		 Reference
Epigallocatechin gallate-loaded phytosome Camellia sinensis Low stability and bioavailability Improved solubility and bioavailability. Physicochemical stability through organoleptic, water content, and physicochemical properties at various temperatures [114]
Rutin-loaded phytosome Citrus
fruits		 Low stability and poor drug release Improved solubility, stability, releasing dynamics and bioavailability in vitro, good antioxidant agent [115]
Soybean seed Phytosome-based thermogel Glycine max L. Low drug absorption and solubility Improved absorption, instability, insolubility, and fast releasing. A clear reduction in body weight, adipose tissue weight, studied in vivo. [116]
Gingerol-loaded phytosome Zingiber officinale Poor stability and drug absorption Improved stability, oral absorption, bioavailability, sustained release, showing potent antioxidant, antibacterial (against Staphylococcus aureus and E. coli), and anti-inflammatory activities in vitro. [117]
Butea monosperma flower extract-loaded phytosome Butea monosperma Poor water solubility and bioavailability Improved solubility, bioavailability, stability, and release dissolution pattern and showed significant free radical scavenging activity in vitro using the DPPH model. [118]
Swertia perennis L.-loaded phytosome Swertia perennis L. Poor drug release profile. Improved entrapment efficiency and in vitro drug release of embedded phytomedicine. [119]
Aloe Vera extract-loaded phytosome Aloe Vera Limited anticancer activity Inhibitory effect on the growth of the MCF-7 cancer cell line, enhanced oral delivery of aloe vera, making its use in cancer therapy. [120]
Morinda lucida extract-loaded phytosome Morinda lucida Limited antimicrobial activities In vivo, anti-plasmodium studies confirmed a higher anti-malarial effect comparable/similar to the standard drug (artesunate). [121]
Aqueous extract of stem bark and lecithin of Tecomella undulata-loaded phytosome Tecomella undulata Poor drug release profile and bioavailability Good entrapment efficiency and drug release in nano sizes (up to 90%), improved bioavailability without resorting to any pharmacological adjuvant or structural modification of the ingredients. [122]

 

As a result, PEGlycated liposomes were found to be the most effective ex vivo transdermal drug delivery technique, effectively decreasing paw edema in the rat model. Table 7 contains other examples.

Table 7. Ethosomes incorporated with herbal medicines. Source: Kumari, et al., 2022

Herbal Drug-Loaded Ethosomes Plant
Source		 Limitations of Free Drugs Results and
Outcomes		 References
Apigenin-loaded ethosomes From many fruits and vegetables such as chamomile Low bioavailability The strong anti-inflammatory activity caused by ultraviolet B light exposure after topical application [125]
Berberis aristata extract-loaded ethosomal gel Berberis
aristata		 Lesser drug penetration and bioavailability Enhanced permeation profile and transdermal delivery of the extract provide a better approach for dermatological disorders [126]
Cryptotanshinone-loaded ethosomal gel Salvia
miltiorrhiza		 Lesser drug penetration and bioavailability Enhanced transdermal flux, skin permeation, and deposition on pigskin in vitro. Improved anti-acne activity with reduced skin irritation in the ear of rabbit model associated with ethosomal gel. [127]
Colchicine trans ethosomal gel From dried corns and seeds of plants of the genus Colchicum Poor stability, solubility drug release bioavailability Improved stability, solubility, sustained release, bioavailability, and skin diffusion in vitro.Enhanced drug accretion, tissue biodistribution, and skin permeation in an ex vivo using Sprague Dawley rats’ back skin [123]
Piperine-loaded ethosomes Piper nigrum Lesser drug penetration and bioavailability Ethosomal cream showed higher deposition in skin layers, non-toxic to HaCat cell lines, and novel drug carrier for management of atopic dermatitis. [128]
Achillea millefolium L.-loaded ethosomes Achillea millefolium L. Limited free radical scavenging activities and drug release Enhanced free radical scavenging activities by about 88%, improved drug release by about 79.8% [129]
Sambucus nigra L. Extract-loaded ethosomes Sambucus
nigra L.		 Cause skin irritation Possessed collagenase inhibition activity, excellent skin compatibility, recognized as a potent cosmeceutical ingredient [130]

 

Sonication, thin-film hydration, micro fluidization, multiple-membrane extrusion, remote loading, reverse-phase evaporation technique, and bubble method are some of the preparation techniques displayed in Figure 9.

Schematic diagram of (a) the methods of preparations of niosomes and (b) the joint process stages in these methods.

Figure 9. Schematic diagram of (a) the methods of preparations of niosomes and (b) the joint process stages in these methods. Image Credit: Kumari, et al., 2022

Table 8. Niosomes loaded with herbal bioactive. Source: Kumari, et al., 2022

Herbal Medicine-Loaded Niosomes Plant
Source		 Limitations of Free Drugs Results and
Outcomes		 References
Permacoce hispida-loaded niosome Permacoce hispida- Poor stability and bioavailability Improved stability, bioavailability, sustained release, and permeability in vitro. Enhanced anti-tuberculosis in vitro. [136]
Embelin-loaded niosome Embelia ribes Burm. Poor stability and bioavailability Improved stability, bioavailability, sustained release, and biocompatibility in vitro. Upgraded streptozotocin-induced diabetes in Albino Wistar rats with potential antioxidant activity. [137]
Lawsone-loaded niosome Persian Henna, Lawsonia inermis Poor stability and bioavailability Improved stability, bioavailability, sustained release, and in vitro permeability. Significantly improved the antitumor activity in MCF-7 cells in vitro. [138]
Rosemarinic acid-loaded niosome Rosmarinus officinalis Limited drug release and drug stability Improved sustained delivery of Niosomal gel of rosmarinic acid to bacteria (Propionibacterium acne and Staphylococcus aureus) infected cells in vitro (anti-acne vulgaris). Improved delivery of naturally occurring antimicrobial and anti-inflammatory agents, in deeper tissues of skin in vivo using Swiss albino mice. [139]
Nerium oleander -loaded niosome Nerium
oleander		 Limited antioxidant activity and bioavailability Improved cell effectiveness and tolerability of active substances. Improved in vitro cytotoxicity toward cervical and alveolar cancer cells (HeLa and A549) using MTT assay. Displayed potential antioxidant activity in vitro using DPPH radical scavenging assay. [140]

 

Two techniques have been developed for the manufacture of cubosomes: top-down and bottom-up (Figure 10). Cubosomes have successfully encapsulated somatostatin, indomethacin, insulin, rifampicin, and other drugs.

Instances of cubosomes integrating herbal bioactives are described in Table 9.

Schematic diagram of (a) the methods of preparations of niosomes and (b) the joint process stages in these methods.

Figure 10. Schematic diagram of (a) the methods of preparations of niosomes and (b) the joint process stages in these methods. Image Credit: Kumari, et al., 2022

Table 9. Niosomes are loaded with herbal bioactive. Source: Kumari, et al., 2022

Herbal Medicine-
Loaded Cubosomes		 Plant
Sources		 Limitations of
Free Drugs		 Results and
Outcomes		 References
Piperine-loaded cubosomes Fruits of the piperaceae family Low stability Improved stability, hydrophobicity, the enhanced and cognitive effect of piperine, displayed anti-inflammatory, anti-apoptotic, and antioxidant effects. [146]
Curcumin-loaded cubosomes Curcuma longa L. Low stability Upgraded stability, production of nanosized vesicles, and enhanced anti-bacterial properties in topical drug delivery. [147]
Achyranthes bidentata-loaded cubosomes Polysaccharides Low stability and immunomodulatory effect Improved stability, immunomodulatory effect, and displayed fewer toxicities to splenic lymphocytes in vitro. [148]
Capsaicin incorporated cubosomes All plants of the capsicum family Cause skin
irritation		 Lowered skin irritation, enhanced stability under light and heat, sustained delivery for transdermal administration of capsaicin. [149]
Essential oil of Citrus trifoliata L. incorporated cubosomes Citrus trifoliata L. Limited insecticidal activities Enhanced insecticidal and fungicidal activities against Fusarium oxysporum, Spodoptera littoralis, and Fusarium solani. [150]

 

Nanotechnology has not only revolutionized medicine, but it has also improved the accuracy and precision with which numerous diseases are treated. It has long been regarded as a superior method for both medication delivery and drug release at the target site.

In addition, tumor killing by heating (hyperthermia), separation and purification of biological molecules and cells, MR imaging contrast enhancement, and phagokinetic investigations are some of the additional medical treatments for cancer diagnosis and therapy.

Nanotechnology allows for advanced therapies with less invasiveness and cost-effective diagnostic equipment that are quicker, lighter, and more sensitive.

The main source of concern is nanoformulation biocompatibility. The simplicity with which nanotechnology-based medicines have been made available at basic levels all across the world and the price of such therapies are the most important factors.

Like any new scientific technique, nanoscience and nanotechnology are the subjects of debate over their utility. 

Conclusion

To summarize, pharmaceutical nanotechnology is a rapidly developing branch of science that aims to improve medication stability, solubility, absorption, and bioavailability in inadequately water-soluble and bioavailable pharmaceuticals. Nanotechnology-based solutions also improve the targeted and sustained administration of the entrapped material, resulting in effective treatment potency with fewer adverse effects.

Journal Reference:

Kumari, S., Goyal, A., Gürer, E. S., Yapar, E. A., Garg, M., Sood, M., Sindhu, R. K. (2022) Bioactive Loaded Novel Nano-Formulations for Targeted Drug Delivery and Their Therapeutic Potential. Pharmaceutics, 14(5), p. 1091. Available online: https://www.mdpi.com/1999-4923/14/5/1091/htm.

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Megan Craig

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Megan Craig

Megan graduated from The University of Manchester with a B.Sc. in Genetics, and decided to pursue an M.Sc. in Science and Health Communication due to her passion for learning about and sharing scientific innovations. During her time at AZoNetwork, Megan has interviewed key Thought Leaders across several scientific, medical and engineering sectors and attended prominent exhibitions worldwide.

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