An Available Strategy for Nasal Brain Transport of Nanocomposite Based on PAMAM Dendrimers via In Situ Gel

Kulkarni

2020

J. Drug Delivery Ther.

Nasal delivery is an alternative to oral or parenteral administration due to certain limitations such as absorption of the drug, drug targeting to particular organs can cause a problem for administration through oral route. The nasal route has also been successfully used for bypassing the blood-brain barrier and afterword delivering drug molecules to the central nervous system. Also, lag time related to oral drug delivery is reduces by this route and offers noninvasiveness, self-medication, patient comfort, and patient compliance. Extend drug delivery can be attained by different new dosage forms like in situ gel. In situ formulations are drug delivery systems. The in-situ gelling system is a process in which the solution forms of a gel before administration in the body, but once administrated, it undergoes gelation in-situ, to form a gel. In situ gelling system becomes very popular nowadays because of their several advantages over conventional drug delivery systems like a sustained and prolonged release of a drug, reduced Frequency of administration, improved patient compliance and comfort. Approaches towards the various formulation of in-situ gel concerning temperature, pH, and physicochemical conditions. The in situ gel-forming polymeric formulations offer several advantages like sustained and prolonged action reduced Frequency of administration, in comparison to conventional drug delivery systems. From a manufacturing point of view, the production of such systems is less complex and thus lowers the investment and manufacturing cost. Various evaluation parameters are considered during the preparation of In-Situ gel. Keywords: Nasal Drug Delivery, In Situ gel, gelation, polymers, etc

“…The final gel quantity was weighed accurately and recorded as W. All measurements were taken at 34°C and tested in triplicate. (13) Water holding capacity = × 100%.…”

Section: ) Critical Ionic Concentration (Cic)mentioning

confidence: 99%

Nasal In Situ Gel: Novel Approach for Nasal Drug Delivery

Kulkarni

2020

J. Drug Delivery Ther.

Pharmaceutical Development and Technology

“…Sodium citrate sequesters free calcium ions, forming complexed calcium form that is then liberated via complex dissociation in the physiological conditions in the buccal cavity, in order to promote instantaneous gelation of gellan gum (Miyazaki et al 1999;Nagarwal and Pandit 2008). From a prolonged delivery perspective, blending gellan gum and HPMC; a semisynthetic cellulose polymer is well-demonstrated in literature in order to conceivably enhance gel structure and strength, augment viscosity and mucoadhesion and retard drug release (Harish et al 2009;Xie et al 2019).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…After cooling to below 40°C, 0.1% of calcium chloride was added into the sol (Harish et al 2009). Freeze-drying A c c e p t e d M a n u s c r i p t of the in situ gel was performed (freeze drying under vacuum for 48h using Chirst, alpha 1-2LD plus, Germany), in order to conduct in vitro characterization tests, namely, morphologic analysis, DSC and FT-IR (Kesavan et al 2010;Xie et al 2019) .…”

Section: Preparation Of Plain In Situ Gelmentioning

confidence: 99%

In situcomposite ion-triggered gellan gum gel incorporating amino methacrylate copolymer microparticles: a therapeutic modality for buccal applicability

Elmowafy

Cespi

Bonacucina

et al. 2019

The aim of the current investigation is to delineate the buccal applicability of an in situ composite gel containing aceclofenac (AC) amino methacrylate copolymer microparticles (MPs), surmounting limitations of oral existing conventional therapy. AC Eudragit RL100 MPs were fabricated and statistically optimized using 2 2 4 1 factorial design. Better buccal applicability and enhanced localization were achieved by combining the optimum MPs with in situ ion-activated gellan gum gel. The crosslinking and gelation of in situ gel were investigated by morphological and solid state characterizations. Suitability for buccal delivery and in vivo therapeutic efficacy in inflammation model of rats were also assessed. Results showed that the best performing formula displayed particle size (PS) of 51.00 µm and high entrapment efficiency (EE%) of 94.73%. MPs were successfully entrapped inside the gel network of the composite system. Gelation tendency, pH, shear-thinning properties and mucoadhesivity of the prepared in situ composite gel guaranteed its buccal suitability. Sustained AC release features and promising in vitro anti-arthritic response were also demonstrated. Moreover, consistent and prolonged in vivo anti-inflammatory effect was achieved, relative to standard AC. Taken together; this study proves the potential of in situ composite gel as an appropriate therapeutic proposal for AC buccal delivery.

“…Although several types of dendrimers have been synthesized and investigated, Poly (amidoamine) (PAMAM) dendrimers were the most widely investigated and commercialized ones. PAMAM dendrimers are highly branched, dendritic, nano-sized polymeric composites with ethylenediamine as the nuclear structure (7). The surface of PAMAM contains plenty of amino groups, which not only provides numerous positive charges but can also be used for functional modification.…”

Section: Introductionmentioning

confidence: 99%

Are PAMAM dendrimers safe for ocular applications? -- Toxicological evaluation in ocular cells and intraocular tissues

Chen

Tang

Wen

et al. 2020

Preprint

Backgrounds: The human eye is a sophisticated and sensitive sensory organ. Due to its dynamic and static barriers, efficient drug therapy for eye diseases is problematic. Polymeric delivery systems have been rapidly developed to overcome this problem, where polymeric dendrimers have received much attention for their unique structures. However, there is insufficient research on whether dendrimer nanomaterials could be used in ophthalmology. Poly (amidoamine) (PAMAM) is a kind of commercialized and extensively used dendrimer. Herein the ocular cytotoxicity and biosafety of PAMAM dendrimers were deeply evaluated by conducting in vitro and in vivo experiments on ocular systems. The effects of generation (G4.0, G5.0, and G6.0) and concentration on cell metabolism, apoptosis, and oxidative damage were carried out. Ocular irritation and intravitreal injection effects were also measured. Results: The results showed that the cytotoxicity of PAMAM increased with increasing generation number. PAMAM at a concentration that below 50 μg/mL was less harmful to the ocular tissues, whereas it caused apparent damage when above 50 μg/mL in the investigated situation. Moreover, singlet oxygen generation was detected in the cells after 50 μg/mL (and above) PAMAM treatment. The in vivo results show that there is no macroscopic structural change observed from fundus and histopathological section images, whereas it shows more functional impairment according to optical coherence tomography (OCT) and electroretinogram (ERG) when treated by 100 μg/mL PAMAM. Conclusion: Overall, a higher concentration of PAMAM, such as above 50 μg/mL, may cause ocular functional damage. The concentrations that are (or lower than) 50 μg/mL showed good biocompatibility and biosafety in human ocular cells and tissues.