Release Of Rifampicin Research Articles

Enhanced eradication of intracellular and biofilm-residing methicillin-resistant Staphylococcus aureus (MRSA) reservoirs with hybrid nanoparticles delivering rifampicin.

Osteomyelitis carries a high risk of recurrence even after extended, aggressive antibiotic therapy. One of the key challenges is to eradicate the reservoirs of methicillin-resistant Staphylococcus aureus (MRSA) inside the host bone cells and their biofilms. Our goal is to develop rifampicin loaded lipid-polymer hybrid nanocarriers (Rf-LPN) and evaluate if they can achieve enhanced rifampicin delivery to eradicate these intracellular and biofilm-residing MRSA. After optimization of the composition, Rf-LPN demonstrated size around 110nm in diameter that remained stable in serum-supplemented medium, drug payload up to 11.7% and sustained rifampicin release for 2weeks. When comparing Rf-LPN with free rifampicin, moderate but significant (p<0.05) improvement of the activities against three osteomyelitis-causing bacteria (USA300-0114, CDC-587, RP-62A) in planktonic form were observed. In comparison, the enhancements in the activities against the biofilms and intracellular MRSA by Rf-LPN were even more substantial. The MBEC50 values against USA300-0114, CDC-587, and RP-62A were 42 vs 155, 70 vs 388, and 265ng/ml vs over 400ng/ml, respectively, and up to 18.5-fold reduction in the intracellular MRSA counts in osteoblasts was obtained. Confocal microscope images confirmed extensive accumulation of Rf-LPN inside the biofilm matrix and MRSA-infected osteoblasts. Overall, in this proof-of-concept study we have developed and validated the strategy to exploit the nanoparticle-cell and nanoparticle-biofilm interactions with a new rifampicin nanoformulation for prevention of osteomyelitis recurrence and chronicity caused by the elusive MRSA.

Formulation and Bioequivalence Testing of Fixed-Dose Combination Orally Disintegrating Tablets for the Treatment of Tuberculosis in the Paediatric Population

Tuberculosis (TB) is believed to affect around 10 million people worldwide. Treatment for TB includes isoniazid and rifampicin, with fixed-dose combination (FDC) recommended for improved patient compliance. Similarly, orally disintegrating tablets (ODTs) are an increasingly popular dosage form that aid compliance since they do not require swallowing. In this study ODTs of isoniazid and rifampicin, either as discrete or FDC doses, were formulated and bioequivalence between single and combination doses compared using in vitro and in silico approaches. Dissolution profiles were compared using FDA advised difference (f1) and similarity (f2) testing in biorelevant media. Rifampicin release from FDCs decreased by approximately 15% in fed-state media (failed f1 and f2), which was attributed to enhanced rifampicin degradation in the presence of isoniazid at lower pH. Apparent permeability (Papp) values derived from Caco-2 transport studies were included alongside dissolution results into a physiologically based pharmacokinetic (PBPK) model, to simulate in vivo bioavailability in healthy subjects. Models showed no difference in bioavailability between formulations or dosing (fasted or fed) state, despite the failures in dissolution-based bioequivalence testing, highlighting shortcomings in f1 and f2 assessment and the strength of PBPK models.

Self assembly and hydrogelation of N-terminal modified tetrapeptide for sustained release and synergistic action of antibacterial drugs against methicillin resistant S. aureus

Self assembly is a ubiquitous process of complex bio-molecules to perform various biological functions. This bottom-up approach applies in engineering of various nanostructures in different technological and biomedical applications. Here we report design and synthesis of phenolic acid conjugated tetra peptides which self assembled in uniform nanofibrils upon dissolution in aqueous solutions at physiological pH and formed stiff and transparent hydrogel. Gel inversion assay, HR-TEM, FT-IR, CD spectroscopy and rheometric analysis characterized the developed hydrogel (HG-2). This gel exhibits characteristics of thixotropy and injectability. Structure-gelation relationship studies of peptide revealed the importance of π-π interactions in self assembly and hydrogelation. Further, this hydrogel used for entrapment and sustained release of antibiotics, rifampicin and ciprofloxacin at physiological pH and temperature for 5 days. The hydrogelator peptide has shown moderate antibacterial activity alone, whereas in combination with rifampicin and ciprofloxacin showed a remarkable synergistic antibacterial activity against clinically relevant multidrug resistant methicillin resistant S. aureus (MRSA). Interestingly, this hydrogel neither cause significant damage to hRBCsnor to human keratinocyte up to hydrogelation concentrations tested by haemolytic and MTT assay. These characteristics of present peptide hold future promising soft materials for treatment of infections and drug delivery applications.

Preparation and evaluation of alginate nanoparticles prepared by green method for drug delivery applications

Nanosized natural polymers have attained considerable attention in drug delivery applications due to their high encapsulation efficiency, non-toxic nature, sustained and targeted drug delivery. Here we have synthesized Rifampicin loaded alginate nanoparticles by green method. Physicochemical characterization of the nanoparticles was assessed using Transmission electron microscopy, Fourier transform infrared spectroscopy, Dynamic light scattering and X-ray diffraction technique. The swelling and in vitro drug release showed that the framework experiences pH-dependent swelling and release of Rifampicin. Rifampicin has lower release in acid medium and higher release in intestinal condition. Moreover, in view of the drug release results, the release kinetics and transport mechanisms were investigated and discussed. In vitro cytotoxicity assay demonstrated that the nanoparticles were non-toxic in nature. The acute oral toxicity study of the synthesized nanoparticles was done in Wistar albino rats. No systemic toxicity was observed after oral administration of nanoparticles. The present study demonstrated the potential of using alginate nanoparticles synthesized by a green method for drug delivery applications.

Versatile poly(vinyl alcohol)/clay physical hydrogels with tailorable structure as potential candidates for wound healing applications.

Physical poly(vinyl alcohol) (PVA) hydrogels containing up to 3% Laponite RD (LRD) were obtained by freezing/thawing method. The structure and the morphology of PVA/LRD hydrogels were evaluated by ATR-FTIR and SEM measurements, respectively. The morphological analysis of the hydrogels revealed the formation of clay agglomerates and large size aggregates at LRD concentrations above 2.5%. The rheological and mechanical properties of the PVA hydrogels in presence/absence of clay and their structural regeneration capacity after a large deformation were also investigated. The effect of LRD incorporation on the swelling behavior of the PVA hydrogels was discussed. The water vapor sorption capacity of PVA hydrogels decreases by clay addition. The analysis of in-vitro rifampicin release data indicated that the presence of a small amount of LRD into hydrogel affects the drug release mechanism. The antimicrobial activity of PVA hydrogels in presence/absence of LRD loaded with rifampicin against Staphylococcus aureus, Escherichia coli and Candida albicans was studied.

Influence of PEGylation on PLGA nanoparticle properties, hydrophobic drug release and interactions with human serum albumin.

To evaluate the impact of PEG content on poly(lactic-co-glycolic acid) (PLGA) NP physicochemical properties, hydrophobic drug release (rifampicin as a modeldrug) and human serum protein binding. Rifampicin loaded and unloaded nanoparticles with PEG content of 0-17% (w/w) were prepared by an emulsification-evaporation technique. Nanoparticles were characterized for size, zeta potential and morphology. PEGlyation was confirmed using proton nuclear magnetic resonance (1H NMR). Fluorescence spectroscopy and dynamic light scattering were used to determine nanoparticle-protein binding, binding constants and stability of nanoparticles in human serum, respectively. Drug loading and release were determined by UV-VIS spectroscopy and drug release data was mathematically modelled. A NP PEG content of 17% w/w significantly retarded release of rifampicin from PLGA NPs and altered kinetics of drug release. Stern-Volmer (Ksv) protein binding constants decreased upon PEG incorporation. A 2% w/w PEG was sufficient to significantly reduce protein binding extent to PLGA NPs and maintain particle size distributions. The ability to fine tune drug release and formation of protein corona around nanoparticles is crucial to formulation scientists. This study suggests that PLGA NPs with low PEG content might be suitable for extended circulation and rapid drug release and that higher PEG content retards hydrophobic drug release.

Mannosylated graphene oxide as macrophage-targeted delivery system for enhanced intracellular M.tuberculosis killing efficiency

Tuberculosis (TB), caused by M.tuberculosis (Mtb), has become a top killer among infectious diseases. Enhancing the ability of anti-TB drugs to kill intracellular Mtb in host cells remains a big challenge. Here, an innovative nano-system was developed to increase drug delivery and Mtb-killing efficacy in Mtb-infected macrophages. We employed mannose surface decoration to develop mannosylated and PEGylated graphene oxide (GO-PEG-MAN). Such nano-platform exhibited increased uptake by macrophages via mannose receptor-mediated endocytosis in vitro. Interestingly, drug-loaded GO-PEG-MAN was preferentially up-taken by mannose receptor-expressing mucosal CD14+ macrophages isolated from Mtb-infected rhesus macaques than drug-loaded GO-PEG. Consistently, the drug concentration was also significantly higher in macrophages than that in T and B cells expressing no or low mannose receptor, implicating a useful macrophage/mannose receptor-targeted drug-delivery system relevant to the in vivo settings. Concurrently, rifampicin-loaded GO-PEG-MAN (Rif@GO-PEG-MAN) significantly increased rifampicin uptake, inducing long-lasting higher concentration of rifampicin in macrophages. Such innovative Rif@GO-PEG-MAN could readily get into the lysosomes of the Mtb host cells, where rifampicin underwent an accelerated release in acidic lysosomic condition, leading to explosive rifampicin release after cell entry for more effective killing of intracellular Mtb. Most importantly, Rif@GO-PEG-MAN-enhanced intracellular rifampicin delivery and pharmacokinetics significantly increased the efficacy of rifampicin-driven killing of intracellular BCG and Mtb bacilli in infected macrophages both in vitro and ex vivo. Such innovative nanocarrier approach may potentially enhance anti-TB drug efficacy and reduce drug side effects.

In vitro controlled release of tuberculosis drugs by amphiphilic branched copolymer nanoparticles

Poly(lactic-co-glycolic acid) (PLGA)-poly ethylene glycol (PEG) based amphiphilic branched copolymer nanoparticles (NPs) have been developed for controlled release of tuberculosis (TB) drugs which include rifampicin (RIF), isoniazid (INH) and pyrazinamide (PYZ). The drug loading efficiency and the percentage drug content of polymer NPs increase by increasing the amount of PEG content in polymer NPs. The branched PLGA-PEG based copolymer NPs exhibit initial burst release followed by sustained release of RIF for 840 h, INH for 72 h, and PYZ for 720 h. The branched citrate-PEG-PLGA copolymer NPs can act as potential drug carriers when compared to their linear analogues.

Glucosamine/L-lactide copolymers as potential carriers for the development of a sustained rifampicin release system using Mycobacterium smegmatis as a tuberculosis model

The present study aims at developing a new, ultrafine particle-based efficient antibiotic delivery system for the treatment of tuberculosis. The carrier material to make the rifampicin (RIF)-loaded particles is a low molecular weight star-shaped polymer produced from glucosamine (core building unit) and L-lactide (GluN-LLA). Particles were made via electrohydrodynamic atomization. Prolonged release (for up to 14 days) of RIF from these particles is reported. Drug release data fits the Korsmeyer-Peppas equation, which suggests the occurrence of a modified diffusion-controlled RIF release mechanism in vitro and is also supported by differential scanning calorimetry and drug leaching tests. Cytotoxicity tests on Mycobacterium smegmatis showed that antibiotic-free GluN-LLA and polylactides (PLA) particles (reference materials) did not show any significant anti-bacterial activity. The minimum inhibitory concentration and minimum bactericidal concentration values obtained for RIF-loaded particles showed 2- to 4-fold improvements in the anti-bacterial activity relative to the free drug. Cytotoxicity tests on macrophages indicated that cell death correlates with an increase of particle concentration but is not significantly affected by material type or particle size. Confocal microscopy was used to track internalization and localization of particles in the macrophages. The uptake of GluN-LLA particles is higher than those of their PLA counterparts. In addition, after phagocytosis, the GluN-LLA particles stayed in the cytoplasm and showed favorable long-term drug release behavior, which facilitated the killing of intracellular bacteria when compared to free RIF. The present studies suggest that these drug carrier materials are potentially very attractive candidates for the development of high-payload, sustained-release antibiotic/resorbable polymer particle systems for treating bacterial lung infections.

Preparation, in vitro release and antibacterial activity evaluation of rifampicin and moxifloxacin-loaded poly(D,L-lactide-co-glycolide) microspheres

Osteomyelitis is difficult to treat because infective bone is poorly accessible for intravenously administering antibiotics and biofilm formation increases bacterial resistance. In this study, microspheres prepared using poly(lactide-co-glycolide) (PLGA) and embedded with moxifloxacin (MOX–PLGA microspheres) and rifampicin/moxifloxacin (RIF/MOX–PLGA microspheres) using the water-in-oil-in-water double emulsion solvent evaporation technique were used for local delivery. Shape of MOX–PLGA microspheres and RIF/MOX–PLGA microspheres were spherical, mean particle size of them were 20.52 μm and 16.62 μm, respectively. Encapsulation efficiency of the MOX-PLGA microspheres was 17.35% ± 2.42%. However, the encapsulation efficiency for MOX and RIF in RIF/MOX–PLGA microspheres was 33.25% ± 7.51% and 49.0% ± 11.25%, respectively. Moxifloxacin and rifampicin were released slowly from microspheres. Both microspheres can efficiently release antibiotics in vitro. Antibacterial and bacterial biofilm-inhibition properties of the released solution were investigated from RIF/MOX–PLGA, MOX–PLGA, and blank PLGA microspheres at varying time points in vitro. RIF/MOX–PLGA microspheres demonstrated the strongest antibacterial activity and bacterial biofilm-inhibition property than the other two microspheres (p < .05). This study suggests that the novel RIF/MOX–PLGA microspheres can be used as a promising carrier for osteomyelitis treatment.

Lipopolysaccharide Polyelectrolyte Complex for Oral Delivery of an Anti-tubercular Drug

Anti-tuberculosis drug delivery has remained a challenge due to inconsistent bioavailability and inadequate sustained-release properties leading to treatment failure. To resolve these drawbacks, a lipopolysaccharide polyelectrolyte complex (PEC) encapsulated with rifampicin (RIF) (as the model drug) was fabricated, using the solvent injection technique (SIT), with soy lecithin (SLCT), and low-molecular-weight chitosan (LWCT). The average particle size and surface charge of RIF-loaded PEC particulates was 151.6nm and + 33.0nm, respectively, with noted decreased particle size and surface charge following increase in SLCT-LWCT mass ratio. Encapsulation efficiency (%EE) and drug-loading capacity (%LC) was 64.25% and 5.84%, respectively. Increase in SLCT-LWCT mass ratio significantly increased %EE with a marginal reduction in %LC. In vitro release studies showed a sustained-release profile for the PEC particulate tablet over 24h (11.4% cumulative release) where the dominant release mechanism involved non-Fickian anomalous transport shifting towards super case II release as SLCT ratios increased (6.4% cumulative release). PEC-tablets prepared without SIT presented with rapid Fickian-diffusion-based drug release with up to 90% RIF release within 4h. Ex vivo permeability studies revealed that lipopolysaccharide PEComplexation significantly increased the permeability of RIF by ~ 2-fold within the 8-h study period. These results suggest successful encapsulation of RIF within a PEC structure while imparting increased amorphic regions, as indicated by x-ray diffraction, for potential benefits in improved drug dissolution, bioavailability, and dosing.

Nanotherapeutic provides dose sparing and improved antimicrobial activity against Brucella melitensis infections

New therapies are needed to treat chronic bacterial diseases and intracellular pathogens, in particular, are very difficult to manage. The use of nanotherapeutics represents an approach to exploit size and charge of biological membranes to overcome barriers for treatment of intracellular pathogens including Brucella melitensis. In this work, polyanhydride nanoparticles comprised of copolymers of sebacic acid, 1,6-bis(p-carboxyphenoxy)hexane, and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane were synthesized to encapsulate antimicrobial compounds doxycycline and rifampicin. The nanoparticles demonstrated sustained release of rifampicin for a week with the antimicrobial activity peaking at 72 h and lasting up to a week. Treatment of B. melitensis infected macrophages with rifampicin-containing nanoparticles rapidly eliminated viable intracellular bacteria following 48 h of treatment and pretreatment with the nano-formulations prevented intracellular infection in contrast to soluble drug controls. Treatment of infected BALB/c mice with a nanoparticle cocktail containing doxycycline and rifampicin for five days decreased bacterial burden by three log10 in the liver. Extended release of antibiotics was demonstrated in vivo by treating B. melitensis infected mice with the standard therapy of daily 0.5 mg doxycycline dose or single 0.5 mg doxycycline-encapsulated nanoparticles delivered once a week. After 3 weeks, bacterial counts in spleen and liver were statistically equal between animals treated with the weekly nano-formulation and daily soluble drug, representing a seven-fold dose sparing. Altogether, these results demonstrated that the use of nanotherapeutics was successful at increasing antimicrobial efficacy and improving in vivo activity through a combination of intracellular delivery, dose sparing, and extended release in treating chronic bacterial infections. This platform technology can also provide benefits for drug delivery against other chronic intracellular bacterial pathogens, including Mycobacterium and Burkholderia species, including treatments against antibiotic-resistant infections.

Structure and function of a novel chitin-uptake channel by marine Vibrio species

The present study aims at developing a new, ultrafine particle-based efficient antibiotic delivery system for the treatment of tuberculosis. The carrier material to make the rifampicin (RIF)-loaded particles is a low molecular weight star-shaped polymer produced from glucosamine (core building unit) and L-lactide (GluN-LLA). Particles were made via electrohydrodynamic atomization. Prolonged release (for up to 14 days) of RIF from these particles is reported. Drug release data fits the Korsmeyer-Peppas equation, which suggests the occurrence of a modified diffusion-controlled RIF release mechanism in vitro and is also supported by differential scanning calorimetry and drug leaching tests. Cytotoxicity tests on Mycobacterium smegmatis showed that antibiotic-free GluN-LLA and polylactides (PLA) particles (reference materials) did not show any significant anti-bacterial activity. The minimum inhibitory concentration and minimum bactericidal concentration values obtained for RIF-loaded particles showed 2- to 4-fold improvements in the anti-bacterial activity relative to the free drug. Cytotoxicity tests on macrophages indicated that cell death correlates with an increase of particle concentration but is not significantly affected by material type or particle size. Confocal microscopy was used to track internalization and localization of particles in the macrophages. The uptake of GluN-LLA particles is higher than those of their PLA counterparts. In addition, after phagocytosis, the GluN-LLA particles stayed in the cytoplasm and showed favorable long-term drug release behavior, which facilitated the killing of intracellular bacteria when compared to free RIF. The present studies suggest that these drug carrier materials are potentially very attractive candidates for the development of high-payload, sustained-release antibiotic/resorbable polymer particle systems for treating bacterial lung infections.

Sonolytically intercalated poly(anisidine-co-toluidine)/bentonite nanocomposites: pH responsive drug release characteristics

With a view to design a drug delivery vehicle for the sustained release of Rifampicin (RIF) – an anti-tuberculosis drug, the present work reports the synthesis of poly (o-anisidine-co-o-toluidine) (PAnis-co-POT) intercalated bentonite nanocomposites via ultrasound-assisted technique. Intercalation as well as copolymerization was confirmed by FT-IR, UV-visible, X-ray diffraction, (XRD). Loading of the copolymer in benotnite clay was confirmed by and thermogravimetric analysis (TGA). Rifampicin (RIF) drug was loaded into the nanocomposite and the release profiles were investigated in gastric (pH 1.2) and intestinal (pH 7.4) fluids. Release followed the zero order kinetics model. The nanocomposites were found to show the sustained release behavior and hold potential to be used as an effective anti-tuberculosis drug delivery vehicle.

Biocompatible Single-Chain Polymer Nanoparticles for Drug Delivery-A Dual Approach.

Single-chain polymer nanoparticles (SCNPs) are protein-inspired materials based on intramolecularly cross-linked polymer chains. We report here the development of SCNPs as uniquely sized nanocarriers that are capable of drug encapsulation independent of the polarity of the employed medium. Synthetic routes are presented for SCNP preparation in both organic and aqueous environments. Importantly, the SCNPs in organic media were successfully rendered water soluble, resulting in two complementary pathways toward water-soluble SCNPs with comparable resultant physicochemical characteristics. The solvatochromic dye Nile red was successfully encapsulated inside the SCNPs following both pathways, enabling probing of the SCNP interior. Moreover, the antibiotic rifampicin was encapsulated in organic medium, the loaded nanocarriers were rendered water soluble, and a controlled release of rifampicin was evidenced. The absence of discernible cytotoxic effects and promising cellular uptake behavior bode well for the application of SCNPs in controlled therapeutics delivery.

Development of Novel Octanoyl Chitosan Nanoparticles for Improved Rifampicin Pulmonary Delivery: Optimization by Factorial Design.

A novel hydrophobic chitosan derivative, octanoyl chitosan (OC) with improved organic solubility was synthesized, characterized, and employed for the preparation of rifampicin (Rif) encapsulated nanoparticle formulations for pulmonary delivery. OC was characterized to confirm acyl group substitution and cytotoxicity in A549 epithelial lung cells. OC nanoparticles were produced by the double emulsion solvent evaporation technique without cross-linking and characterized for particle size distribution, morphology, crystallinity, thermal stability, aerosol delivery, and drug release rate. OC was successfully synthesized with substitution degree of 44.05 ± 1.75%, and solubility in a range of organic solvents. Preliminary cytotoxicity studies of OC showed no effect on cell viability over a period of 24h on A549 cell lines. OC nanoparticles were optimized using a 32 full factorial design. An optimized batch of OC nanoparticles, smooth and spherical in morphology, had mean hydrodynamic diameter of 253 ± 19.06nm (PDI 0.323 ± 0.059) and entrapment efficiency of 64.86 ± 7.73% for rifampicin. Pulmonary deposition studies in a two-stage impinger following aerosolization of nanoparticles from a jet nebulizer gave a fine particle fraction of 43.27 ± 4.24%. In vitro release studies indicated sustained release (73.14 ± 3.17%) of rifampicin from OC nanoparticles over 72h, with particles demonstrating physical stability over 2months. In summary, the results confirmed the suitability of the developed systems for pulmonary delivery of drugs with excellent aerosolization properties and sustained-release characteristics.

Comparative study of oral lipid nanoparticle formulations (LNFs) for chemical stabilization of antitubercular drugs: physicochemical and cellular evaluation

Rifampicin (RIF) and Isoniazid (INH) are two major first-line antitubercular drugs (ATDs) that are typically administered orally, in combination. However, INH-catalysed degradation of RIF under acidic pH environment of the stomach is a major concern related to its oral delivery, and is dramatically accelerated upon further exposure to and interaction with INH. This interaction, in turn, triggers a direct decline in the available RIF dose below the sub-therapeutic level, thereby diminishing its therapeutic efficacy. We hypothesized that encapsulation of both these important ATDs into lipid nanoparticle formulations (LNFs) may help mitigate the acid hydrolysis of RIF, its subsequent interaction with INH and its eventual INH-mediated accelerated chemical degradation in the gastric environment. We further hypothesized that these LNFs would be capable of enhanced uptake and localization into intra-cellular compartments of lung macrophages, thereby potentially targeting the Tb pathogen in its in vivo niche. For this purpose, we evaluated two promising LNFs, viz., solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for encapsulating these ATDs. Here, we report on the design, development and comparative evaluation of SLN and NLC-based lipid formulations of both INH and RIF. Our strategy of nanoencapsulation substantially prolonged encapsulated RIF release and improved its chemical stability in presence of INH in a simulated gastric acidic environment. In vitro cell culture studies showed a well-quantifiable uptake of LNFs in a human alveolar macrophage cell line. Overall, these evaluations provided promising results for establishing the potential of both formulations for TB therapy.

Development of respirable rifampicin-loaded nano-lipomer composites by microemulsion-spray drying for pulmonary delivery

The purpose of this study was to develop respirable rifampicin (RIF) loaded nano-lipomer (lipid/polymer) composites for pulmonary delivery to increase the availability of drug at local site, and enhance the residence time of drug in the lungs and thereby improving the therapy. Rifampicin-loaded nano-lipid polymer (nano-lipomer) composites were prepared by a microemulsion-spray dry technique and were characterized for particle size, thermal stability, polymorphic transitions and chemical integrity. Furthermore, the lipomer were screened for their surface morphology and in vitro rifampicin release behavior in simulated lung fluid (artificial lysosomal fluid (ALF) at pH 4.5 and Gamble's solution at a pH of 7.4) represent different interstitial environment in the lung. The particle sizes of the lipomer were ranged between 382.5 ± 6.033 to 561.8 ± 4.965 nm with a narrow polydispersity index (0.315 ± 0.023 to 0.424 ± 0.033) and zeta potential (−32.5 ± 1.206 to −26.5 ± 1.211 mV). Rifampicin entrapment efficiency was between 61.25 ± 1.049 to 73.14 ± 1.048% and SEM images revealed well-separated, sphere-shaped and smooth surface lipomer. DSC and XRD analysis of lipomer corroborated that the formulations were in an amorphous state. New nano-lipomer formulated with different ratios of lipid and polymer exhibited a rapid dissolution by an initial burst release of RIF followed by a controlled release profile.

Interactions of mussel-inspired polymeric nanoparticles with gastric mucin: Implications for gastro-retentive drug delivery

Mussel-inspired polydopamine (pD) coatings have several unique characteristics such as durability, versatility, and robustness. In this study, we have designed pD-coated nanoparticles (NPs) of methoxy polyethylene glycol-b-poly(ε-caprolactone) (mPEG-PCL@pD) as prospective nanoscale mucoadhesive platforms for gastro-retentive drug delivery. Successful pD coating on the NPs was confirmed by Transmission Electron Microscopy and X-ray Photoelectron Spectroscopy. Mucoadhesion of pD-coated NPs was investigated in vitro using commercially available mucin under stomach lumen-mimetic conditions. Mucin-NP interactions were monitored by dynamic light scattering, which showed a significant change in particle size distribution of pD-coated NPs at mucin/NP ratios of 1:1, 1:2, and 1:4w/w. Turbidity measurements indicated the formation of large mucin-NP aggregates causing a significant increase in turbidity at mucin/NP ratios of 2:1 and 4:1w/w. pD-coated NPs exhibited a significantly higher mucin adsorption ability compared to uncoated NPs at mucin/NP ratios of 1:4, 1:2, and 1:1w/w. Zeta potential measurements demonstrated that mucin-pD-coated NP interactions were not electrostatic in nature. An ex vivo wash-off test conducted using excised sheep stomach revealed that 78% of pD-coated NPs remained attached to the mucosa after 8h of incubation, compared to only 33% of uncoated NPs. In vitro release of rifampicin, used as a model drug, showed a similar controlled release profile from both pD-coated and uncoated NPs. Our results serve to expand the versatility of mussel-inspired coatings to the design of mucoadhesive nanoscale vehicles for oral drug delivery.

Effectively Rifampicin loaded microspheres based on blends of high- and low-molecular-mass polylactic acid

Specific features of immobilization of Rifampicin drug by poly-D,L-lactic acid microparticles and the possibility of controlling the uniform Rifampicin release were studied.