Potential enhancement of metformin hydrochloride in solidified reverse micellar solution-based PEGylated lipid nanoparticles targeting therapeutic efficacy in diabetes treatment.

Metformin hydrochloride (MH) is a widely used oral biguanide antihyperglycemic (antidiabetic) drug with poor bioavailability which necessitates the development of novel drug delivery systems such as PEGylated solid lipid nanoparticles for improving its therapeutic activity. The aim of this study was to formulate, characterize and evaluate in vitro and in vivo pharmacodynamic properties of metformin-loaded PEGylated solid lipid nanoparticles (PEG-SLN) for improved delivery of MH. The lipid matrices (non-PEGylated lipid matrix and PEGylated lipid matrices) used in the formulation of both non-PEGylated (J0) and PEGylated SLNs (J10, J20, J40) were prepared by fusion using beeswax and Phospholipon ® 90H at 7:3 ratio with or without polyethylene glycol (PEG) 4000 (0, 10, 20 and 40% w/w), respectively. Representative lipid matrices (LM and PEG-LM) were loaded with MH by fusion and then characterized by differential scanning calorimetry (DSC) and Fourier transform infrared (FT-IR) spectroscopy. The PEG-SLNs were prepared by high shear hot homogenization using the lipid matrices (5% w/w), drug (MH) (1.0% w/w), sorbitol (4% w/w) (cryoprotectant), Tween ® 80 (2% w/w) (surfactant) and distilled water (q.s to 100% w/w) (vehicle). The non-PEGylated and PEGylated SLNs (J0, J10, J20, J40)) were characterized with respect to encapsulation efficiency (EE%), loading capacity (LC), morphology by scanning electron microscopy (SEM), mean particle size (Zav) and polydispersity indices (PDI) by photon correlation spectroscopy (PCS), compatibility by FT-IR spectroscopy and in vitro drug release in biorelevant medium. Thereafter, in vivo antidiabetic study was carried out in alloxanized rats' model and compared with controls (pure sample of MH and commercial MH- Glucophage®)). Solid state characterizations indicated the amorphous nature of MH in the drug loaded-lipid matrices. The PEG-SLNs were mostly smooth and spherical nanoformulations with Zav and PDI of 350.00 nm and 0.54, respectively, for non-PEGylated SLNs, and in the range of 386.80-783.10 nm and 0.592 to 0.752, respectively, for PEGylated SLNs. The highest EE% and LC were noted in batch J20 and were 99.28% and 16.57, respectively. There was no strong chemical interaction between the drug and excipients used in the preparation of the formulations. The PEGylated SLN (batch J40) exhibited the highest percentage drug released (60%) at 8 h. The PEGylated SLNs showed greater hyperglycemic control than the marketed formulation (Glucophage ®) after 24 h. This study has shown that metformin-loaded PEGylated solid lipid nanoparticles could be employed as a potential approach to improve the delivery of MH in oral diabetic management, thus encouraging further development of the formulations.

Enhanced circulation longevity and pharmacodynamics of metformin from surface-modified nanostructured lipid carriers based on solidified reverse micellar solutions.

Metformin hydrochloride (MTH) has been associated with poor/incomplete absorption (50-60%), low bioavailability, short half-life (0.4-0.5 h), high dosage and dose-related side effects. To overcome these barriers and improve oral bioavailability and efficacy of MTH, surface-modified nanostructured lipid carriers (NLCs) were developed. Lipid matrices composed of rational blends of beeswax and Phospholipon® 90H (as solid lipids) and Capryol-PGE 860 (as liquid lipid) were prepared by fusion, and the resultant lipid matrices were PEGylated to give 10, 20 and 40% PEGylated lipid matrices. MTH-loaded non-PEGylated and PEGylated NLCs were prepared via high-shear hot homogenization and characterized regarding particle properties and physicochemical performance. The encapsulation efficiencies (EE%) and loading capacities (LC) of the MTH-loaded NLCs were determined while the in vitro drug release was evaluated in phosphate buffered saline (PBS, pH 7.4). Antidiabetic and pharmacokinetics properties of the NLCs were ascertained in an alloxan-induced diabetic rats model after oral administration. The MTH-loaded NLCs were nanomeric (particle size: 184.8-882.50 nm) with low polydispersity index (0.368-0.687) and zeta potential (26.5-34.2 mV), irregular shape, amorphous nature with reduced crystallinity. The EE% and LC were >90 % and 16%, respectively. The formulations showed >65 % release over 12 h in a greater sustained manner than marketed MTH formulation (Glucophage®) as well as enhanced pharmacokinetics properties and sustained blood glucose lowering effect, even at reduced doses with PEGylated NLCs than Glucophage®. Thus, PEGylated NLC is a promising approach for improved delivery and oral bioavailability of MTH thus encouraging further development of the formulation.

Recent and advanced nano-technological strategies for COVID-19 vaccine development.

The outbreak of the COVID-19 pandemic in 2019 has been one of the greatest challenges modern medicine and science has ever faced. It has affected millions of people around the world and altered human life and activities as we once knew. The high prevalence as well as an extended period of incubations which usually does not present with symptoms have played a formidable role in the transmission and infection of millions. A lot of research has been carried out on developing suitable treatment and effective preventive measures for the control of the pandemic. Preventive strategies which include social distancing, use of masks, washing of hands, and contact tracing have been effective in slowing the spread of the virus; however, the infectious nature of the SARS-COV-2 has made these strategies unable to eradicate its spread. In addition, the continuous increase in the number of cases and death, as well as the appearance of several variants of the virus, has necessitated the development of effective and safe vaccines in a bid to ensure that human activities can return to normalcy. Nanotechnology has been of great benefit in the design of vaccines as nano-sized materials have been known to aid the safe and effective delivery of antigens as well as serve as suitable adjuvants to potentiate responses to vaccines. There are only four vaccine candidates currently approved for use in humans while many other candidates are at various levels of development. This review seeks to provide updated information on the current nano-technological strategies employed in the development of COVID-19 vaccines.

Development of lipid-based microsuspensions for improved ophthalmic delivery of gentamicin sulphate.

Aim: Anterior eye segment disorders are treated with eye drops and ointments, which have low ocular bioavailability necessitating the need for improved alternatives. Lipid microsuspension of gentamicin sulphate was developed for the treatment of susceptible eye diseases. Materials & methods: Lipid microsuspensions encapsulating gentamicin sulphate were produced by hot homogenization and evaluated. Ex vivo permeation and ocular irritancy tests were also conducted. Results & conclusion: Stable microsuspensions with high entrapment efficiency and satisfactory osmolarities were obtained. Release studies achieved 49-88% in vitro release at 12 h with sustained permeability of gentamicin compared with conventional gentamicin eye drop (Evril®). No irritation was observed following Draize's test. The microsuspensions have great potential as ocular delivery system of gentamicin sulphate.

Improved antimalarial activity of caprol-based nanostructured lipid carriers encapsulating artemether-lumefantrine for oral administration.

BACKGROUND: Artemether and lumefantrine display low aqueous solubility leading to poor release profile; hence the need for the use of lipid-based systems to improve their oral bioavailability so as to improve their therapeutic efficacy. AIM AND OBJECTIVE: The objective of this work was to utilize potentials of nanostructured lipid carriers (NLCs) for improvement of the oral bioavailability of artemether and lumefantrine combination and to evaluate its efficacy in the treatment of malaria. This study reports a method of formulation, characterization and evaluation of the therapeutic efficacies of caprol-based NLC delivery systems with artemether and lumefantrine. METHOD: The artemether-lumefantrine co-loaded NLCs were prepared using the lipid matrix (5% w/w) (containing beeswax and Phospholipon® 90H and Caprol-PGE 860), artemether (0.1%w/w) and lumefantrine (0.6%w/w), sorbitol (4%w/w), Tween® 80(2%w/w as surfactant) and distilled water (q.s to 100%) by high shear homogenization and evaluated for physicochemical performance. The in vivo antimalarial activities of the NLC were tested in chloroquine-sensitive strains of Plasmodium berghei (NK-65) using Peter´s 4-day suppressive protocol in mice and compared with controls. Histopathological studies were also carried out on major organs implicated in malaria. RESULTS: The NLC showed fairly polydispersed nano-sized formulation (z-average:188.6 nm; polydispersity index, PDI=0.462) with no major interaction occurring between the components while the in vivo study showed a gradual but sustained drug release from the NLC compared with that seen with chloroquine sulphate and Coartem®. Results of histopathological investigations also revealed more organ damage with the untreated groups than groups treated with the formulations. CONCLUSION: This study has shown the potential of caprol-based NLCs for significant improvement in oral bioavailability and hence antimalarial activity of poorly soluble artemether and lumefantrine. Importantly, this would improve patient compliance due to decrease in dosing frequency as a sustained release formulation.

Novel Intravaginal Drug Delivery System Based on Molecularly PEGylated Lipid Matrices for Improved Antifungal Activity of Miconazole Nitrate.

The aim of this study was to investigate the potential of microparticles based on biocompatible phytolipids [Softisan® 154 (SF) (hydrogenated palm oil) and super-refined sunseed oil (SO)] and polyethylene glycol- (PEG-) 4000 to improve intravaginal delivery of miconazole nitrate (MN) for effective treatment of vulvovaginal candidiasis (VVC). Lipid matrices (LMs) consisting of rational blends of SF and SO with or without PEG-4000 were prepared by fusion and characterized and employed to formulate MN-loaded solid lipid microparticles (SLMs) by melt-homogenization. The SLMs were characterized for physicochemical properties, anticandidal activity, and stability. Spherical discrete microparticles with good physicochemical properties and mean diameters suitable for vaginal drug delivery were obtained. Formulations based on SO:SF (1:9) and containing highest concentrations of PEG-4000 (4 %w/w) and MN (3.0 %w/w) were stable and gave highest encapsulation efficiency (83.05-87.75%) and inhibition zone diameter (25.87±0.94-26.33±0.94 mm) and significantly (p<0.05) faster and more powerful fungicidal activity regarding killing rate constant values (7.10 x 10-3-1.09 x 10-2 min-1) than commercial topical solution of MN (Fungusol®) (8.00 x 10-3 min-1) and pure MN sample (5.160 x 10-3 min-1). This study has shown that MN-loaded SLMs based on molecularly PEGylated lipid matrices could provide a better option to deal with VVC.

Phospholipon 90H (P90H)-based PEGylated microscopic lipospheres delivery system for gentamicin: an antibiotic evaluation.

OBJECTIVE: To formulate gentamicin liposphere by solvent-melting method using lipids and polyethylene glycol 4 000 (PEG-4 000) for oral administration. METHODS: Gentamicin lipospheres were prepared by melt-emulsification using 30% w/w Phospholipon® 90H in Beeswax as the lipid matrix containing PEG-4 000. These lipospheres were characterized by evaluating on encapsulation efficiency, loading capacity, change in pH and the release profile. Antimicrobial activities were evaluated against Escherichia coli, Pseudomonas aeruginosa, Salmonella paratyphii and Staphylococcus aureus using the agar diffusion method. RESULTS: Photomicrographs revealed spherical particles within a micrometer range with minimal growth after 1 month. The release of gentamicin in vitro varied widely with the PEG-4 000 contents. Moreover, significant (P>0.05) amount of gentamicin was released in vivo from the formulation. The encapsulation and loading capacity were all high, indicating the ability of the lipids to take up the drug. The antimicrobial activities were very high especially against Pseudomonas compare to other test organisms. This strongly suggested that the formulation retain its bioactive characteristics. CONCLUSIONS: This study strongly suggest that the issue of gentamicin stability and poor absorption in oral formulation could be adequately addressed by tactical engineering of lipid drug delivery systems such as lipospheres.