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Cubosomes are lipid vesicles that are comparable to vesicular systems like liposomes. Cubosomes are created with certain amphiphilic lipids in the presence of a suitable stabiliser. Since its discovery and designation, self-assembled cubosomes as active drug delivery vehicles have drawn much attention and interest. Oral, ocular, transdermal, and chemotherapeutic are just a few of the drug delivery methods in which they are used. Cubosomes show tremendous potential in drug nanoformulations for cancer therapeutics because of their prospective advantages, which include high drug dispersal due to the structure of the cubic, large surface area, a relatively simple manufacturing process, biodegradability, ability to encapsulate hydrophobic, hydrophilic, and amphiphilic compounds, targeted and controlled release of bioactive agents, and biodegradability of lipids. The most typical technique of preparation is the simple emulsification of a monoglyceride with a polymer, followed by sonication and homogenisation. Top-down and bottom-up are two different sorts of preparation techniques. This review will critically analyse the composition, preparation techniques, drug encapsulation approaches, drug loading, release mechanism and applications relevant to cubosomes. Furthermore, the challenges faced in optimising various parameters to enhance the loading capacities and future potentialities are also addressed.

Numerous attempts to overcome the poor water solubility of cam ptothecin (CPT) by various nano drug delivery systems are described in various sources in the literature. However, the results of these approaches may be hampered by the incomplete separation of free CPT from the formulations, and this issue has not been investigated in detail. This study aimed to promote the solubility and continuous delivery of CPT by developing long-lasting liposomes using various weights (M.W. 2000 and 5000 Daltons) of the hydrophilic polymer polyethylene glycol (PEG). Conventional and PEGylated liposomes containing CPT were formulated via the lipid film hydration method (solvent evaporation) using a rotary flash evaporator after optimising various formulation parameters. The following physicochemical characteristics were investigated: surface morphology, particle size, encapsulation efficiency, in vitro release, and formulation stability. Different molecular weights of PEG were used to improve the encapsulation efficiency and particle size. The stealth liposomes prepared with PEG5000 were discrete in shape and with a higher encapsulation efficiency (83 ± 0.4%) and a prolonged rate of drug release (32.2% in 9 h) compared with conventional liposomes (64.8 ± 0.8% and 52.4%, respectively) and stealth liposomes containing PEG2000 (79.00 ± 0.4% and 45.3%, respectively). Furthermore, the stealth liposomes prepared with PEG5000 were highly stable at refrigeration temperature. Significant changes were observed using various pharmacokinetic parameters (mean residence time (MRT), half-life, elimination rate, volume of distribution, clearance, and area under the curve) of stealth liposomes containing PEG2000 and PEG5000 compared with conventional liposomes. The stealth liposomes prepared with PEG5000 showed promising results with a slow rate of release over a long period compared with conventional liposomes and liposomes prepared with PEG2000, with altered tissue distribution and pharmacokinetic parameters.

The present study was carried out to develop cisplatin-loaded chitosan nanoparticles (CCNP) and cisplatin-loaded chitosan nanoparticle surface linked to rituximab (mAbCCNP) as targeted delivery formulations. The two formulations (CCNP and mAbCCNP) exhibited significant physicochemical properties. The zetapotential (ZP) values of CCNP and mAbCCNP were 30.50 ± 5.64 and 26.90 ± 9.09 mV, respectively; while their particle sizes were 308.10 ± 1.10 and 349.40 ± 3.20 z.d.nm, respectively. The poly dispersity index (PDI) of CCNP was 0.257 ± 0.030 (66.6% PDI), while that of mAbCCNP was 0.444 ± 0.007 (57.60% PDI). Differential scanning calorimetry (DSC) revealed that CCNP had endothermic peaks at temperatures ranging from 135.50 to 157.69 °C. A sharp exothermic peak was observed at 95.79 °C, and an endothermic peak was observed at 166.60 °C. The XRD study on CCNP and mAbCCNP revealed distinct peaks at 2θ . Four peaks at 35.38°, 37.47°, 49.29°, and 59.94° corresponded to CCNP, while three distinct peaks at 36.6°, 49.12°, and 55.08° corresponded to mAbCCNP. The in vitro release of cisplatin from nanoparticles followed zero order kinetics in both CCNP and mAbCCNP. The profile for CCNP showed 43.80% release of cisplatin in 6 h (R 2  = 0.9322), indicating linearity of release with minimal deviation. However, the release profile of mAbCCNP showed 22.52% release in 4 h (R 2  = 0.9416), indicating linearity with sustained release. In vitro cytotoxicity studies on MCF-7 ATCC human breast cancer cell line showed that CCNP exerted good cytotoxicity, with IC 50 of 4.085 ± 0.065 µg/mL. However, mAbCCNP did not elicit any cytotoxic effect. At a dose of 4.00 µg/mL cisplatin induced early apoptosis and late apoptosis, chromatin condensation, while it produced secondary necrosis at a dose of 8.00 µg/mL. Potential delivery system for cisplatin CCNP and mAbCCNP were successfully formulated. The results indicated that CCNP was a more successful formulation than mAbCCNP due to lack of specificity of rituximab against MCF-7 ATCC human breast cancer cells.

Current research aimed to develop nanocubosomes co-loaded with dual anticancer drugs curcumin and temozolomide for effective colon cancer therapy. Drugs co-loaded nanocubosomal dispersion was prepared by modified emulsification method using glyceryl monooleate (GMO), pluronic F127 and bovine serum albumin (BSA) as a lipid phase, surfactant, and stabilizer, respectively. The resulting nanocubosomes were characterized by measuring hydrodynamic particle size, particle size distribution (PSD), drug loading capacity (DL), encapsulation efficiency (EE), colloidal stability and drug release profile. We also physiochemically characterized the nanocubosomes by transmission electron microscopy (TEM), Fourier transform infrared (FTIR), and x-rays diffraction (XRD) for their morphology, polymer drug interaction and its nature, respectively. Further, the in-vitro cell-uptake, mechanism of cell-uptake, in-vitro anti-tumor efficacy and apoptosis level were evaluated using HCT-116 colon cancer cells. The prepared nanocubosomes exhibited a small hydrodynamic particle size (PS of 150 ± 10 nm in diameter) with nearly cubic shape and appropriate polydispersity index (PDI), enhanced drug loading capacity (LC of 6.82 ± 2.03% (Cur) and 9.65 ± 1.53% (TMZ), high entrapment efficiency (EE of 67.43 ± 2.16% (Cur) and 75.55 ± 3.25% (TMZ), pH-triggered drug release profile and higher colloidal stability in various physiological medium. Moreover, the nanocubosomes showed higher cellular uptake, in-vitro cytotoxicity and apoptosis compared to free drugs, curcumin and temozolomide, most likely because its small particle size. In addition, BSA-stabilized nanocubosomes were actively taken by aggressive colon cancer cells that over-expressed the albumin receptors and utilized BSA as nutrient source for their growth. In short, this study provides a new and simple strategy to improve the efficacy and simultaneously overawed the adaptive treatment tolerance in colon cancer.

Drug delivery using oral route is the most popular, convenient, safest and least expensive approach. It includes oral transmucosal delivery of bioactive compounds as the mucosal cavity offers an intriguing approach for systemic drug distribution. Owing to the dense vascular architecture and high blood flow, oral mucosal layers are easily permeable and can be an ideal site for drug administration. Recently, the transmucosal route is being investigated for other therapeutic candidates such as vaccines for their efficient delivery. Vaccines have the potential to trigger immune reactions and can act as both prophylactic and therapeutic conduit to a variety of diseases. Administration of vaccines using transmucosal route offers multiple advantages, the most important one being the needle-free (non-invasive) delivery. Development of needle-free devices are the most recent and pioneering breakthrough in the delivery of drugs and vaccines, enabling patients to avoid needles, reducing anxiety, pain and fear as well as improving compliance. Oral, nasal and aerosol vaccination is a novel immunization approach that utilizes a nanocarrier to administer the vaccine. Nanocarriers improve the bioavailability and serve as adjuvants to elicit a stronger immune response, resulting in increased effectiveness of vaccination. Drugs and vaccines with lower penetration abilities can also be delivered transmucosally while maintaining their biological function. The development of micro/nanocarriers for transmucosal delivery of macromolecules, vaccines and other substances is currently drawing much attention and a number of studies were performed recently. This comprehensive review is aimed to summarize the most recent investigations on needle-free and non-invasive approaches for the delivery of vaccines using oral transmucosal route, their strengths and associated challenges. The oral transmucosal vaccine delivery by nanocarriers is the most upcoming advancement in efficient vaccine delivery and this review would help further research and trials in this field.

Essential oils (EOs) are known for their diverse bioactivities, including antioxidant, anti-inflammatory, antibacterial, antifungal, antiviral, skin-barrier repairing and anticancer, and therefore, hold profound potential to be used in cosmetic and skincare products. Owing to these properties, EOs have long been utilized to address a range of dermatological issues, from acne and inflammation to aging and dryness. However, problems associated with EOs beset their practical applications, which include high volatility, oxidation, hydrophobic nature, low bioavailability, skin irritation, chemical transformation and poor stability in air and light. A prospective of nanolipidic formulations, including the nanostructured lipid carriers (NLCs) and solid lipid nanoparticles (SLNs) system for improved skin delivery of these EOs highlights the possibility of their use in topical applications, which offer several advantages such as improved bioavailability and stability, lower toxicity and higher drug content. These nanoformulations protect the EOs from environmental degradation and improve their penetration into deeper skin layers, leading to prolonged therapeutic benefits. The delivery of bioactive agents using a conventional topical preparation exhibits low penetration, frequent applications, poor adherence and prolonged therapy duration, whereas the novel delivery system exhibits improved stability of the drug, enhanced skin penetration, enhanced retention and better therapeutic efficacy. This review provides a comprehensive compendium of information on EOs, which are widely used in skincare, along with their nanolipidic formulations for maximized skincare uses. The mechanism of action of EOs as skin bioactive agents, challenges associated with their use, advances in nanolipidic formulations and their market value as cosmetic skincare products are also explored.

Agarose (AG) is a naturally occurring biocompatible marine seaweed extract that is converted to hydrocolloid gel in hot water with notable gel strength. Currently, its mucoadhesion properties have not been fully explored. Therefore, the main aim of this study was to evaluate the mucoadhesive potential of AG binary dispersions in combination with Carbopol 934P (CP) as mucoadhesive gel preparations. The gels fabricated via homogenization were evaluated for ex vivo mucoadhesion, swelling index (SI), dissolution and stability studies. The mucoadhesive properties of AG were concentration dependent and it was improved by the addition of CP. Maximum mucoadhesive strength (MS) (27.03 g), mucoadhesive flow time (FT) (192.2 min), mucoadhesive time in volunteers (MT) (203.2 min) and SI (23.6% at 4 h) were observed with formulation F9. The mucoadhesive time investigated in volunteers (MT) was influenced by AG concentration and was greater than corresponding FT values. Formulations containing 0.3%, w/v AG (F3 and F9) were able to sustain the release (~99%) for both drugs till 3 h. The optimized formulation (F9) did not evoke any inflammation, irritation or pain in the buccal cavity of healthy volunteers and was also stable up to 6 months. Therefore, AG could be considered a natural and potential polymer with profound mucoadhesive properties to deliver drugs through the mucosal route.

The goal of an antiviral agent research is to find an antiviral drug that reduces viral growth without harming healthy cells. Transformations of the virus, new viral strain developments, the resistance of viral pathogens, and side effects are the current challenges in terms of discovering antiviral drugs. The time has come and it is now essential to discover a natural antiviral agent that has the potential to destroy viruses without causing resistance or other unintended side effects. The pharmacological potency of thymoquinone (TQ) against different communicable and non-communicable diseases has been proven by various studies, and TQ is considered to be a safe antiviral substitute. Adjunctive immunomodulatory effects in addition to the antiviral potency of TQ makes it a major compound against viral infection through modulating the production of nitric oxide and reactive oxygen species, decreasing the cytokine storm, and inhibiting endothelial dysfunction. Nevertheless, TQ’s low oral bioavailability, short half-life, poor water solubility, and conventional formulation are barriers to achieving its optimal pharmacologic benefits. Nano-formulation proposes numerous ways to overcome these obstacles through a small particle size, a big surface area, and a variety of surface modifications. Nano-based pharmaceutical innovations to combat viral infections using TQ are a promising approach to treating surmounting viral infections.

The present study aimed to develop a local dental nanoemulgel formulation of Nigella sativa oil (NSO) for the treatment of periodontal diseases. NSO purchased from a local market was characterized using a GC–MS technique. A nanoemulsion containing NSO was prepared and incorporated into a methylcellulose gel base to develop the nanoemulgel formulation. The developed formulation was optimized using a Box–Behnken statistical design (quadratic model) with 17 runs. The effects of independent factors, such as water, oil, and polymer concentrations, were studied on two dependent responses, pH and viscosity. The optimized formulation was further evaluated for droplet size, drug release, stability, and antimicrobial efficacy. The developed formulation had a pH of 7.37, viscosity of 2343 cp, and droplet size of 342 ± 36.6 nm. Sustained release of the drug from the gel for up to 8 h was observed, which followed Higuchi release kinetics with non-Fickian diffusion. The developed nanoemulgel formulation showed improved antimicrobial activity compared to the plain NSO. Given the increasing emergence of periodontal diseases and antimicrobial resistance, an effective formulation based on a natural antibacterial agent is warranted as a dental therapeutic agent.

The purpose of this study was to develop a novel nano antibacterial formulation of dextran sulfate sodium polymer. The dextran sulfate sodium (DSS) nanoparticles were formulated with gelation technique. The nanoparticles exhibited significant physicochemical and effective antibacterial properties, with zeta potential of − 35.2 mV, particle size of 69.3 z d nm, polydispersity index of 0.6, and percentage polydispersity of 77.8. The DSS nanoparticles were stable up to 102 °C. Differential scanning calorimetry revealed an endothermic peak at 165.77 °C in 12.46 min, while XRD analysis at 2 θ depicted various peaks at 21.56°, 33.37°, 38.73°, 47.17°, 52.96°, and 58.42°, indicating discrete nanoparticle formation. Antibacterial studies showed that the DSS nanoparticles were effective against Gram-positive and Gram-negative bacteria. The minimum inhibitory concentrations of DSS nanoparticles for Bacillus subtilis ( B. subtilis ), Staphylococcus aureus ( S. aureus ), Streptococcus pyogenes ( S. pyogenes ), Escherichia coli ( E. coli ), Pseudomonas aeruginosa ( P. aeruginosa ), Klebsiella pneumoniae ( K. pneumoniae ) and Proteus vulgaris ( P. vulgaris ) were 150, 200, 250, 150, 200, 250, 250 µg/mL, respectively . The antibacterial effects of DSS nanoparticles were in the order E. coli (26 ± 1.2 mm) at 150 µg/mL >  S. pyogenes (24.6 ± 0.8 mm) at 250 µg/mL >  B. subtilis (23.5 ± 2 mm) at 150 µg/mL >  K. pneumoniae (22 ± 2 mm) at 250 µg/mL >  P. aeruginosa (21.8 ± 1 mm) at 200 µg/mL >  S. aureus (20.8 ± 1 mm) at 200 µg/mL >  P. vulgaris (20.5 ± 0.9 mm) at 250 µg/mL. These results demonstrate the antibacterial potency of DSS injectable nanoparticles.