Retraction notice to "Mechanistic insight into the bioactivity of prodigiosin-entrapped lipid nanoparticles against triple-negative breast, lung and colon cancer cell lines" [Heliyon 9 (2023) e16963].

[This retracts the article DOI: 10.1016/j.heliyon.2023.e16963.].

The Role of Bacteriophages in the Gut Microbiota: Implications for Human Health.

Bacteriophages (phages) are nano-sized viruses characterized by their inherent ability to live off bacteria. They utilize diverse mechanisms to absorb and gain entry into the bacterial cell wall via the release of viral genetic material, which uses the replication mechanisms of the host bacteria to produce and release daughter progeny virions that attack the surrounding host cells. They possess specific characteristics, including specificity for particular or closely related bacterial species. They have many applications, including as potential alternatives to antibiotics against multi-resistant bacterial pathogens and as control agents in bacteria-contaminated environments. They are ubiquitously abundant in nature and have diverse biota, including in the gut. Gut microbiota describes the community and interactions of microorganisms within the intestine. As with bacteria, parasitic bacteriophages constantly interact with the host bacterial cells within the gut system and have obvious implications for human health. However, it is imperative to understand these interactions as they open up possible applicable techniques to control gut-implicated bacterial diseases. Thus, this review aims to explore the interactions of bacteriophages with bacterial communities in the gut and their current and potential impacts on human health.

Mechanistic insight into the bioactivity of prodigiosin-entrapped lipid nanoparticles against triple-negative breast, lung and colon cancer cell lines.

This research investigates the potentials of prodigiosin(PG) derived from bacteria and its formulations against triple-negative breast (TNB), lung, and colon cancer cells. The PG was extracted from S. marcescens using continuous batch culture, characterized, and formulated into lyophilized parenteral nanoparticles (PNPs). The formulations were characterized with respect to entrapment efficiency (EE), DSC, FT-IR, TEM, and proton nuclear magnetic resonance (1H NMR) spectroscopy. In vitro drug release was evaluated in phosphate buffer (pH 7.4) while acute toxicity, hematological and histopathological studies were performed on rats. The in vitro cytotoxicity was evaluated against TNB (MCF-7), lung (A-549), and colon (HT-29) cancer cell lines. High EE (92.3 ± 12%) and drug release of up to 89.4% within 8 h were obtained. DSC thermograms of PG and PG-PNPs showed endothermic peaks indicating amorphous nature. The FT-IR spectrum of PG-PNPs revealed remarkable peaks of pure PG, indicating no strong chemical interaction between the drug and excipients. The TEM micrograph of the PG-PNPs showed nano-sized formulations (20-30 nm) whose particles were mostly lamellar and hexagonal structures. The 1H NMR result revealed the chemical structure of PG showing all assigned proton chemical shifts. Toxicity results of the PG and its formulation up to a concentration of 5000 mg/kg showed insignificant vacuolar changes of hepatocytes in the liver, with normal renal medulla and cortex in the kidney. The PG and PG-PNPs inhibited the growth of breast, lung, and colon cell lines. The nano-sized lipid formulation (PG-PNPs) showed potential in PG delivery and cancer treatments.

Overcoming Challenges in Pediatric Formulation with a Patient-Centric Design Approach: A Proof-of-Concept Study on the Design of an Oral Solution of a Bitter Drug.

Designing oral formulations for children is very challenging, especially considering their peculiarities and preferences. The choice of excipients, dosing volume and palatability are key issues of pediatric oral liquid medicines. The purpose of the present study is to develop an oral pediatric solution of a model bitter drug (ranitidine) following a patient centric design process which includes the definition of a target product profile (TPP). To conclude on the matching of the developed solution to TPP, its chemical and microbiological stability was analyzed over 30 days (stored at 4 °C and room temperature). Simulation of use was accomplished by removing a sample with a syringe every day. Taste masking was assessed by an electronic tongue. The developed formulation relied on a simple taste masking strategy consisting in a mixture of sweeteners (sodium saccharine and aspartame) and 0.1% sodium chloride, which allowed a higher bitterness masking effectiveness in comparison with simple syrup. The ranitidine solution was stable for 30 days stored at 4 °C. However, differences were noted between the stability protocols (unopened recipient and in-use stability) showing the contribution of the simulation of use to the formation of degradation products. Stock solution was subjected to acid and alkali hydrolysis, chemical oxidation, heat degradation and a photo degradation stability assessment. The developed pediatric solution matched the TPP in all dimensions, namely composition suitable for children, preparation and handling adapted to hospital pharmaceutical compounding and adequate stability and quality. According to the results, in-use stability protocols should be preferred in the stability evaluation of pediatric formulations.

Exploitation of capsule system for colon targeted drug delivery of biopolymer-based microparticles: in vivo and in vitro applications.

The current study was to improve and control aceclofenac delivery prepared as biopolymer-based microparticles for effective colon-targeted drug delivery using modified gelatin capsules (MGCs) at different time intervals developed in two batches (C1 and C2). Microparticles were formulated with extracted mucuna gum using liquid paraffin oil (AC.LPO) and soybean oil (AC.SO) and evaluated in vitro for physicochemical performance and in vivo in rats. Encapsulation efficiency ranges from 54.48 ± 0.21% to 82.83 ± 0.22% for AC.LPO and 52.64 ± 0.11% to 80.36 ± 0.22% for AC.SO. SEM showed oblong and irregular shapes with porous and cracked surfaces. DSC showed low enthalpy and a very broad endothermic peak depicting high amorphous property. Delayed drug release was observed in the upper gastrointestinal tract with sustained release depicted in the lower gastrointestinal tract (GIT) using 3 and 9-h batch C1 of MGCs. AC.SO exhibited significantly (p < 0.05) higher anti-inflammatory activity (86%) than AC.LPO (77%). Hence, aceclofenac colon delivery could be improved and controlled using biopolymer-based colon-targeted microparticles delivered with MGCs.

Nanogels as target drug delivery systems in cancer therapy: A review of the last decade.

Cancer is an important cause of morbidity and mortality worldwide, irrespective of the level of human development. Globally, it was estimated that there were 19.3 million new cases of cancer and almost 10 million deaths from cancer in 2020. The importance of prevention, early detection as well as effective cancer therapies cannot be over-emphasized. One of the important strategies in cancer therapy is targeted drug delivery to the specific tumor sites. Nanogels are among the several drug delivery systems (DDS) being explored as potential candidates for targeted drug delivery in cancer therapy. Nanogels, which are new generation, versatile DDS with the possession of dual characteristics of hydrogels and nanoparticles have shown great potential as targeted DDS in cancer therapy. Nanogels are hydrogels with a three-dimensional (3D) tunable porous structure and a particle size in the nanometre range, from 20 to 200 nm. They have been visualized as ideal DDS with enormous drug loading capacity, and high stability. Nanogels can be modified to achieve active targeting and enhance drug accumulation in disease sites. They can be designed to be stimulus-responsive, and react to internal or external stimuli such as pH, temperature, light, redox, thus resulting in the controlled release of loaded drug. This prevents drug accumulation in non-target tissues and minimizes the side effects of the drug. Drugs with severe adverse effects, short circulation half-life, and easy degradability by enzymes, such as anti-cancer drugs, and proteins, are suitable for delivery by chemically cross-linked or physically assembled nanogel systems. This systematic review summarizes the evolution of nanogels for targeted drug delivery for cancer therapy over the last decade. On-going clinical trials and recent applications of nanogels as targeted DDS for cancer therapy will be discussed in detail. The review will be concluded with discussions on safety and regulatory considerations as well as future research prospects of nanogel-targeted drug delivery for cancer therapy.

Biosurfactant Production Using Mutant Strains of Pseudomonas aeruginosa and Bacillus subtilis from Agro-industrial Wastes.

Purpose: Biosurfactants are applied in drug formulations to improve drug solubility and in some cases, treat diseases. This study is focused on generating, extracting, purifying and then characterizing biosurfactants from bacterial isolates of palm oil wastes and abattoir soil origins. Methods: Eight bacteria were isolated from the soil and sludge samples, out of which four (50%) were found to produce biosurfactants. Bacillus subtilis (37.5%) and Pseudomonas aeruginosa (50%) were isolated and identified from these samples using mineral salt medium, nutrient agar and Cetrimide agar. Mutant isolates of B. subtilis BS3 and P. aeruginosa PS2 were used to produce biosurfactants using mineral salt medium as enrichment medium and extraction was done using membrane filter. Results: The mutant strains B. subtilis BS3 and P. aeruginosa PS2 generated biosurfactants that displayed significant solubility and dissolution properties by enhancing the percentage solubility of piroxicam to 62.86 and 54.29% respectively, and achieved 51.71 and 48.71% dissolution of the drug in 0.1N HCl. Conclusion: From the results obtained, the produced biosurfactants could serve as a better alternative to conventional surfactants. Notably, the study indicated that the biosurfactant produced by mutant strain of B. subtilis produced more potent activities (surface tension reduction ability, high emulsification) than those of P. aeruginosa.

Formulation and evaluation of transdermal nanogel for delivery of artemether.

Artemether (ART) is second to artesunate in being the most widely used derivatives of artemisinin in combination therapy of malaria. Nanostructured lipid carrier (NLC) formulations were prepared following our previous report using optimized ART concentration of 0.25 g dissolved in 5% w/v mixture of solid (Gelucire 43/01 and Phospholipon 85G) and liquid (Transcutol) lipids at 90 °C. An aqueous surfactant phase at 90 °C was added (dropwise) under magnetic stirring (1000 rpm) for 5 min. The pre-emulsion was speedily homogenized at 28,000 rpm for 15 min and further probe sonicated at 60% amplitude (15 min). Resultant sample was cooled at room temperature and frozen at - 80 °C prior to lyophilization. The freeze-dried sample was used for solid-state characterization as well as in the formulation of transdermal nanogels using three polymers (Carbopol 971P, Poloxamer 407, and Prosopis africana peel powder) to embed the ART-NLC, using ethanol as a penetration enhancer. Transdermal ART-nanogels were characterized accordingly (physical examination, pH, drug content, rheology, spreadability, stability, particle size and morphology, skin irritation, in vitro and ex vivo skin permeation, and analysis of permeation data), P < 0.05. Results indicated that ART nanogels showed good encapsulation, drug release, pH-dependent swelling, stability, and tolerability. Overall, ART nanogels prepared from Poloxamer 407 showed the most desirable drug permeation, pH, swellability, spreadability, viscosity, and transdermal antiplasmodial properties superior to PAPP-ANG > C971P-ANG. A two-patch/week concurrent application of the studied nanogels could offer 100% cure of malaria as a lower-dose (50 mg ART) patient-friendly regimen devoid of the drug's many side effects.

Evaluation of the Properties of Encapsulated Stavudine Microparticulate Lipid-based Drug Delivery System in Immunocompromised Wistar Rats.

BACKGROUND: Lipid-based formulations have been confirmed to lower some side effects of drugs and can be tailor-made to offer sustained drug release of drugs with short half-life like stavudine. AIM: This study aimed to evaluate the immunomodulatory properties of stavudine-loaded solid lipid microparticles (SLMs) using immunocompromised Wistar rats. METHODS: The SLMs were formulated by the homogenization method. The optimized batches were used for further in vivo studies. The effect of formulation on the CD4 count and the haematological properties of immunocompromised Wistar rats were studied. RESULTS: The particle size range was 4 -8 µm, EE range was 85-93 % and maximum drug release was observed at 10 h. The CD4 cells increased from 115 ± 3.17 cell/mm3 at day zero to 495 ± 5.64 cell/mm3 at day 14 of treatment and 538 ± 6.31 cell/mm3 at day 21. The red blood cells increased from 2.64 ± 1.58 (x 106/mm3) at day zero to 6.96 ± 3.47 (x 106/mm3) at day 14 and 7.85 ± 3.64 (x 106/mm3) at day 21. PCV increased significantly (p < 0.05) to about 42-50 % at day 21 in the groups that received the SLMs formulations. White blood cells (WBC) also were 12 x 103/mm3, for SLM formulations, while the rats that received plain stavudine exhibited WBC of 9.6 x 103/mm3 at day 21. The histopathological studies revealed that oral stavudine-loaded SLMs had no significant damage to the kidney, liver, spleen and the brain of Wistar rats. CONCLUSION: The formulations exhibited significantly higher immunomodulatory properties than plain stavudine (p<0.05) and showed good properties for once daily oral administration and could be a better alternative to plain stavudine tablets for the management of patients living with HIV.

Anti-Inflammatory and Gastroprotective Properties of Aspirin - Entrapped Solid Lipid Microparticles.

BACKGROUND: Aspirin is a nonsteroidal anti-inflammatory drug that is very effective in the treatment of inflammation and other health conditions, however, it causes gastric irritation. Recently, researchers have developed patents (US9757529, 2019) of inhalable aspirin for rapid absorption and circumvention of gastric irritation. OBJECTIVE: The aim of this work was to formulate aspirin-loaded lipid based formulation in order to enhance oral bioavailability and inhibit gastric irritation. METHODS: This solid lipid microparticles loaded with aspirin (SLM) was formulated by a modified cold homogenization-solvent evaporation method. In vitro studies such as in vitro drug release, particle size, Encapsulation Efficiency (EE), micromeritic properties and loading capacity were carried out. Pharmacodynamics studies such as anti-inflammatory and ulcerative properties of the SLM were also carried out in Wistar rats. RESULTS: The results showed that aspirin entrapped SLM exhibited the highest EE of 72% and particle size range of 7.60 + 0.141µm to 20.25 + 0.070µm. Formulations had about 55% drug release at 6h in simulated intestinal fluid pH 6.8. The formulations had good flowability that could facilitate filling into hard gelatin capsule shells. The SLM exhibited 100% gastroprotection against aspirin-induced ulcers (p < 0.05). The percentage of anti-inflammatory activities also showed that aspirin-entrapped SLM had 78% oedema inhibition at 7h, while the reference had 68% inhibition at 7h. CONCLUSION: Aspirin-entrapped SLM showed good sustained-release properties, enhanced antiinflammatory properties and total gastric protection from aspirin-induced ulcers and could be used as once-daily oral aspirin.

Insulin-loaded mucoadhesive nanoparticles based on mucin-chitosan complexes for oral delivery and diabetes treatment.

In this study, insulin-loaded nanoparticles (NPs) were prepared via self-gelation method using chitosan and aqueous soluble snail mucin as natural polymers. Herein, mucins were ionically interacted with chitosan at different concentrations to obtained insulin-loaded NPs, labelled as A1 (1:1) (i.e., chitosan 2 % w/v + mucin 2 % w/v) and A2 (2:1) (chitosan 4 % w/v + mucin 2 % w/v), using poloxamer and poly vinyl alcohol as solid surfactant. Such formulation was selected to provide the necessary dynamics for the formation of the nanoparticles while maintaining the surface properties that will favor the encapsulation of insulin. Each system was characterized in terms of their particle size distribution, morphology, zeta potential, and polydispersity index. In vitro release of insulin was evaluated in acidic solution (pH 1.2) and phosphate buffer solution (pH 7.4), and the hypoglycaemic activity was evaluated in diabetes rats. The prepared insulin-loaded NPs displayed particles with relatively smooth surfaces and an average particle size of 479.6 and 504.1 nm for A1 and A2, respectively. Zeta potential and polydispersity index, ranged from 22.1 to 31.2 mV and 0.155-0.185, respectively. The encapsulating efficiency for the systems A1 and A2 were 88.6 and 92.5, respectively, and a self-sustained release of encapsulated insulin was observed for over a period of 8 h. In vivo studies revealed a pronounced hypoglycaemic effect in diabetic rats after peroral administration of the insulin-loaded NPs compared to the effect caused by free oral insulin solution. In addition, both the pharmacokinetic and toxicity results showed low plasma clearance of insulin and no signs of toxicity on the liver enzyme and cell viability, which suggested good biocompatibility of the NPs formulations. Overall, the formation of NPs of insulin with chitosan and snail mucin represents a potentially safe and promising approach to protect insulin and enhance its peroral delivery.

Preliminary studies on the formulation of immune stimulating complexes using saponin from Carica papaya leaves.

There have been several modifications in the use of immune stimulating complexes as adjuvants, such as the replacement of phospholipids with saponin content. Not much research has been done on the use of local alternatives. This actually instigated the use of a local alternative saponin source from Carica papaya leaves to formulate Iscomatrix adjuvant. The Iscomatrix samples used in this study were formulated using different methods (the rapid injection, the reversed rapid injection, the slow/dropwise injection and the reversed slow/dropwise injection methods). Furthermore, the quantity of the components was also varied. These formulated samples were compared with other adjuvants and analysed for their ability to induce antibody and cell mediated immune responses using animal model i.e. mice. The results showed that the Iscomatrix samples formulated, were able to induce significant humoral and antibody mediated immune response (ranging from 16.7 % - 38.88 %) and they also elicited cell mediated immune response (ranging from 8.33 % - 16.7 %) when compared to the models that were administered with antigen only. Further characterizations were made, such as pH, UV scanning, Scanning Electron Microscopy. The analysis revealed that the samples were slightly soluble in distilled water with a neutral pH ranging from 7.26 - 7.43. The UV analysis also indicated that they all had a close range of absorption peaks (between 266.8-269.37 nm). Saponin from Carica papaya leaves can be used to formulate Iscomatrix adjuvant capable of stimulating cell mediated and antibody mediated immune responses.

A new lipid-based oral delivery system of erythromycin for prolong sustain release activity.

Erythromycin-loaded solid lipid microparticles (SLM) based on solidified reverse micellar solution (SRMS) as an oral delivery formulation was studied. Hot homogenization technique was employed to prepare erythromycin stearate-loaded SLMs using blends of Softisan® 154 and Phospholipon® 90H or beeswax in the ratio of 1:2, and characterized in vitro. Antibacterial evaluation of the formulations was carried out by agar diffusion technique against some selected clinical isolates of bacterial. Preliminary pharmacokinetic study was performed after oral administration in male Albino rats. The results of matrix contain Softisan® 154 and phospholipon® 90H (1:2) showed that erythromycin-loaded SLM was smooth; particle size ranged from 10.3 ±â€¯11.24 µm to 18.1 ±â€¯10.11 µm and maximum encapsulation efficiency and loading capacity were 95.11 ±â€¯0.3% and 43.22 ±â€¯0.1 mg, respectively. While that of beeswax- containing matrix showed maximum particle size of 18.9 ±â€¯21.10 µm, maximum encapsulation efficiency of 89.01 ±â€¯0.11% and loading capacity of 39.02 ±â€¯0.12 mg. All the formulations had prolonged release and antibacterial activity. Significantly (p > 0.05), prolonged plasma erythromycin concentration was obtained in the optimized formulation (>14 h) compared with commercial sample of erythromycin tablet (10h). Erythromycin stearate-loaded SLMs formulation could serve as an alternative to conventional oral formulation of erythromycin.

Surface-modified mucoadhesive microgels as a controlled release system for miconazole nitrate to improve localized treatment of vulvovaginal candidiasis.

The use of conventional vaginal formulations of miconazole nitrate (MN) in the treatment of deep-seated VVC (vulvovaginal candidiasis) is limited by poor penetration capacity and low solubility of MN, short residence time and irritation at the application site. Surface-modified mucoadhesive microgels were developed to minimize local irritation, enhance penetration capacity and solubility and prolong localized vaginal delivery of MN for effective treatment of deep-seated VVC. Solid lipid microparticles (SLMs) were prepared from matrices consisting of hydrogenated palm oil (Softisan® 154, SF) and super-refined sunseed oil (SO) with or without polyethylene glycol (PEG)-4000, characterized for physicochemical performance and used to prepare mucoadhesive microgels (MMs) encapsulating MN, employing Polycarbophil as bioadhesive polymer. The MMs were evaluated for physicochemical performance and in vitro drug release in simulated vaginal fluid (pH=4.2), whereas mucoadhesive, rheological and stability tests, anticandidal efficacy in immunosuppressed estrogen-dependent female rats and vaginal tolerance test in rabbits were performed with optimized formulation. The amorphicity of 1:9 phytolipid blend (SO:SF) was increased in the presence of PEG-4000. The physicochemical properties of the SLMs and MMs indicated their suitability for vaginal drug delivery. Overall, MN-loaded PEGylated MMs exhibited significantly (p<0.05) more prolonged drug release than non-PEGylated MMs. Additionally, optimized PEGylated MMs was stable at 40±2°C over a period of 6months, viscoelastic, mucoadhesive, non-sensitizing, histopathologically safe and gave remarkably (p<0.05) higher reduction in Candida albicans load (86.06%) than Daktarin® (75.0%) and MN-loaded polymeric-hydrogel (47.74%) in treated rats in 12days. Thus, PEGylated MMs is promising for effective and convenient treatment of VVC.

Improved dissolution and anti-inflammatory activity of ibuprofen-polyethylene glycol 8000 solid dispersion systems.

BACKGROUND: The purpose of this study was to develop ibuprofen (IB)-polyethylene glycol (PEG) 8000 solid dispersions (SDs) and investigate them for in vitro dissolution and in vivo anti-inflammatory activity. MATERIALS AND METHODS: IB-PEG 8000 SDs were prepared by fusion method using varying combination ratios of IB and PEG 8000. Characterization based on surface morphology, particle size, absolute drug content, and Fourier transform infrared (FT-IR) spectroscopy was carried out on the SDs. The in vitro release of IB from the SDs was performed in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.4) without enzymes, whereas the anti-inflammatory activity was evaluated using egg albumin-induced rat paw edema model. RESULTS: Greenish brown, discrete, and irregularly shaped SDs of mean particle size range 113.5 ± 2.5-252.5 ± 1.9 µm, which were stable over 3 months, were obtained. The drug content of the SDs ranged from 73.4 ± 2.9 % to 83.5 ± 2.7%. Although the drug content increased with increased concentration of PEG 8000 in the SDs, the mean particle size decreased with increased concentration of PEG 8000 in the SDs. The FT-IR results indicate no strong chemical interaction of IB and PEG 8000 in the SDs. There was marked increase in the dissolution rate of IB from the SDs (P < 0.05) as compared to pure IB and physical mixture. The dissolution was better in SIF than in SGF. The increased dissolution rate of IB may be due to the formation of microcrystals, increased wettability and dispersibility in PEG 8000. The SDs showed good anti-inflammatory properties achieving up to 90% edema inhibition at 6 h while the pure sample of IB had 77% edema inhibition at 6 h. CONCLUSION: SDs based on IB-PEG 8000 is a good approach to enhance the dissolution rate and anti-inflammatory activity of IB, thus, encouraging further development of the SDs.

Investigation of novel solid lipid microparticles based on homolipids from Bos indicus for the delivery of gentamicin.

BACKGROUND: The aim of this study was to formulate solidified reverse micellar solution (SRMS)-based solid lipid microparticles (SLMs) using homolipids from tallow fat (Bos indicus) and evaluate its potential for enhanced delivery of gentamicin. MATERIALS AND METHODS: SLMs were formulated by melt-emulsification using SRMS (15% w/w Phospholipon(®) 90G in 35% w/w Bos indicus), polyethylene glycol 4000 (PEG) and gentamicin (1.0, 2.0, 3.0% w/w), and characterized with respect to size, morphology, encapsulation efficiency % and pH-dependent stability. The in vitro release of gentamicin from the SLMs was performed in phosphate buffer (pH 7.4) while bioevaluation was carried out using clinical isolates of Staphylococcus aureus and Escherichia coli. RESULTS: Results showed that the lipid matrix accommodated gentamicin in a concentration-dependent manner, and that stable and spherical SLMs with size range of 18.62 ± 1.24-20.59 ± 1.36 µm and 21.35 ± 1.57-50.62 ± 2.37 µm respectively for unloaded and drug-loaded formulations were obtained. The in vitro drug release studies revealed that SRMS-based SLMs could better be used to control the release of gentamicin than gentamicin injection. Results of sensitivity test revealed that the SLMs time-dependently and capacity-limitedly produced greater inhibition zone diameters (IZDs) than the standards, an indication of improved bioactivity against the test organisms, with greater IZDs against S. aureus than E. coli. Overall, SLMs containing 2% w/w SRMS, 3% w/w gentamicin and PEG 4000 entrapped the highest amount of drug, achieved complete drug release and gave highest IZD against the organisms within 420 min, while plain gentamicin gave the least. CONCLUSION: This research has shown that SLMs based on Bos indicus and P90G is a potential carrier system for dissolution and bioactivity enhancement of gentamicin.

The use of solid lipid nanoparticles for sustained drug release.

Novel solid lipid drug delivery systems such as solid lipid nanoparticles (SLN) have attracted wide and increasing attention in recent years. It has been sought as an interesting alternative drug delivery carrier system for bioactives for a variety of delivery routes. They show major advantages such as sustained release, improved bioavailability, improved drug incorporation and very wide application. This paper presents a discussion on the production protocols of SLN, lyophilization of SLN and delivery of SLN across the blood-brain barrier. Special attention was also paid to entrapment and release of drugs from SLN and strategies to enhance drug entrapment in SLN for sustained release. Analytical methods for the characterization of SLN were also discussed. Various routes of administration of SLN were presented as well as a consideration of the ethical issues and future prospects in the production and use of SLN for sustained release of bioactives.

Formulation, in vitro and in vivo evaluation of halofantrine-loaded solid lipid microparticles.

CONTEXT: Formulation, characterization, in vitro and in vivo evaluation of halofantrine-loaded solid lipid microparticles (SLMs). OBJECTIVE: The objective of the study was to formulate and evaluate halofantrine-loaded SLMs. MATERIALS AND METHODS: Formulations of halofantrine-loaded SLMs were prepared by hot homogenization and thereafter lyophilized and characterized using particle size, pH stability, loading capacity (LC) and encapsulation efficiency (EE). In vitro release of halofantrine (Hf) from the optimized SLMs was performed in SIF and SGF. In vivo study using Peter's Four day suppressive protocol in mice and the mice thereafter subjected to histological studies in kidney and liver. RESULTS: Results obtained indicated that EE of 76.32% and 61.43% were obtained for the SLMs containing 7% and 3% of Hf respectively. The SLMs loaded with 3% of Hf had the highest yield of 73.33%. Time-dependent pH stability analysis showed little variations in pH ranging from 3.49 ± 0.04 to 4.03 ± 0.05. DISCUSSION: The SLMs showed pH-dependent release profile; in SIF (43.5% of the drug for each of H2 and H3) compared with SGF (13 and 18% for H2 and H3 respectively) after 8 h. The optimized SLMs formulation and Halfan® produced a percentage reduction in parasitemia of 72.96% and 85.71% respectively. The histological studies revealed that the SLMs formulations have no harmful effects on the kidney and liver. CONCLUSION: SLMs formulations might be an alternative for patients with parasitemia as there were no harmful effects on vital organs of the mice.

Formulation, characterization and anti-malarial activity of homolipid-based artemether microparticles.

The anti-malarial activity of artemether is dependent on its bioavailability. The purpose of the research is to improve the solubility, bioavailability and therapeutic efficacy of lipophilic artemether using homolipid-based microparticles. Irvingia fat was extracted from Irvingia gabonensis var. excelsa (Irvingia wombolu), and its lipid matrices (LM) with Phospholipon(®) 90G (P90G) were characterized by differential scanning calorimetry (DSC) and wide angle X-ray diffraction (WAXD). Solid lipid microparticles were formulated, characterized, filled and compressed into capsules and tablets, respectively, and drug release studied. In vivo anti-plasmodial activity of artemether SLMs was evaluated in mice. The crystallinity of the phyto-lipid reduced in the presence of P90G, which was integrated into the irvingia fat crystal lattice. SLM dispersions with 3:1 irvingia fat/P90G composition showed higher diffusion and permeability through dialysis membrane while lower proportion of P90G (9:1 LM) favored increased dissolution rate of artemether from capsules (p<0.05). Significant increase (p<0.05) in % plasmodial growth inhibition and reduced parasitemia were observed in mice administered with the SLM dispersions compared with the controls. Therefore, SLMs prepared with composite mixtures of a homolipid and P90G could be used to improve the solubility, dissolution, permeability, bioavailability and anti-malarial efficacy of artemether.

Solid lipid micro-dispersions (SLMs) based on PEGylated solidified reverse micellar solutions (SRMS): a novel carrier system for gentamicin.

The purpose of this study was to formulate and evaluate novel PEGylated solidified reverse micellar solutions (SRMS)-based solid lipid microparticles (SLMs) for improved delivery of gentamicin. Lipid matrix (SRMS) [consisting of 15% w/w Phospholipon® 90G (P90G) in 35% w/w dika wax (Irvingia gabonensis) was formulated and characterized by differential scanning calorimetry (DSC). SLMs were formulated by melt-emulsification using the SRMS, PEG 4000 and gentamicin (1.0, 2.0, 3.0% w/w), and their physicochemical as well as pharmacokinetic parameters determined. In vitro permeation of gentamicin from the SLMs through artificial membrane (0.22 µm pore size) was carried out using Franz's cell and phosphate-buffered saline (PBS, pH 7.4) as acceptor medium, while bioevaluation was performed using clinical isolates of Pseudomonas aeruginosa and Staphylococcus aureus. Stable and irregularly-shaped gentamicin-loaded SLMs of size range 34.49 ± 2.56 to 53.52 ± 3.09 µm were obtained. The SLMs showed sustained drug permeation and exhibited time-dependent and capacity-limited bioactivity. Overall, SLMs containing 2% w/w SRMS, 3% w/w gentamicin and PEG 4000 entrapped the highest amount of drug, gave highest IZD against the test organisms and highest permeation flux (5.239 µg/cm(2).min) and permeation coefficient (1.781 × 10(-6)cm/min) within 420 min, while pure gentamicin gave the least. Preliminary in vivo pharmacokinetic studies also showed an AUC-24 of 1507 µg/h/ml for the optimized formulation, while that of oral drug solution was 678 µg/h/ml. This showed a 2.2-fold increase in the systemic bioavailability of gentamicin from the optimized formulation. PEGylated SRMS-based SLMs prepared with heterolipid from Irvingia gabonensis would likely offer a reliable delivery system for gentamicin.