Table 6 Various in situ gel systems

Moxifloxacin hydrochloride

Methylcellulose, carbopol 934P, poloxamer 407, gellan gum

A formulation containing gellan gum 0.245% w/v, poloxamer 407 19.072% w/v shows gelling time 102 s, temperature 36 °C and drug release 98% at 9 h

[17]

Ornidazole and doxycycline hyclate

Chitosan-vanillin cross-linked polymer, pluronic F127 (P127) and pluronic F68 (P68)

In the treatment of periodontal pocket infection microspheres loaded in situ gel (MLIG) implant gives various desired properties in one system including biodegradability, biocompatibility, stability, syringebility, mucoadhesivity, prolonged release, patients compliant, and cost-effective.

[16]

Levofloxacin (LVF) and metronidazole (MZ)

Poloxamer 407, chitosan

A combination of chitosan 1.5% w/v and poloxamer 407 gives mucoadhesive, thermoresponsive, and controlled release of drugs up to 48 h.

[74]

Simvastatin

Poloxamer 407, methylcellulose

A combination of 25% poloxamer 407 and 5% methylcellulose gives thermoresponsive injectable gel at body temperature. It also gives a controlled release of drug up to 10 days.

[75]

Curcumin

Pluronic F127 (30% w/v), carbopol P934 (1% w/v)

1% w/v of carbopol P934 and 30% w/v of pluronic F127 give double response (pH sensitive and thermoresponsive) in one system.

[76]

Levofloxacin and metronidazole

Chitosan

In the periodontal disease treatment, chitosan is effective as well as is a good carrier for drug delivery.

[77]

Articaine hydrochloride

Pluronic F-127, HPMC K-100/carbopol 934P

A combination of articaine hydrochloride (4% w/w), pluronic F-127 (20% w/w), and hydroxyl propyl methyl cellulose (0.1% w/w) gives prolonged analgesia or local anesthesia, thermoresponsive, and sustained release of drug respectively.

[15]

Doxycycline hyclate

Bleached shellac, agarose, hexane, glyceryl monostearate, dimethyl sulfoxide, N-methyl pyrrolidone, 2-pyrrolidone

All in situ gel gives their solvent release more than 7 days with release rate order DMSO > NMP > PYR. Among these solvents, PYR is best because drug release is effectively retarded from in situ gel and in situ microparticle due to the high viscosity of bleached shellac in PYR.

[78]

Doxycycline hyclate

Glyceryl monostearate, dimethyl sulfoxide, N-methyl pyrrolidone, 2-pyrrolidone

Thermal degradation of the polymer could delay, due to their high intermolecular strength. In situ microparticles of glyceryl monostearate with DMSO give delayed thermal degradation.

[79]

Doxycycline hyclate

Bleached shellac, dimethyl sulfoxide, N-methyl pyrrolidone, 2-pyrrolidone

By dissolving of bleached shellac in dimethyl sulfoxide, NMP, PYR, and in a eutectic mixture, in situ forming gels can be prepared. The result was as follows: viscosity, eutectic mixture > PYR > DMSO > NMP and velocity of gel formation, DMSO > NMP > PYR > eutectic mixture. Slow exchange of solvent and highest degradation was the problems with the PYR solvent. Preparation of eutectic mixture cannot be given by needles due to their high apparent viscosity.

[80]

Doxycycline hyclate

Eudragid RS, N-methyl pyrrolidone, clove oil

The addition of clove oil retarded the solvent exchange and prolonged the release of doxycycline hyclate from Eudragid RS in situ gel. When the amount of Eudragid RS was increased then the transformation of liquid to gel was more rapid during in vitro testing.

[57]

Chlorhexidinedihydrochloride

PLGA, HPMC, N-methyl pyrrolidone

Loss of formulation accidentally from gingival pockets can be reduced in comparison with available commercial products in the market.

[63]

Metronidazole

Glycerol monooleate, N-methyl pyrrolidone

In the treatment of CP (chronic periodontitis), reduced side effects and enhanced bioavailability achieved by using the intra pocket system of lyotropic liquid crystal.

[81]

Doxycycline hyclate

Bleached shellac, N-methyl pyrrolidone, dimethyl sulfoxide, 2-pyrrolidone, glyceryl monostearate

P. gingivalis, S. aureus, and S. mutans are effectively inhibited by doxycycline hyclate-loaded bleached shellac in situ microparticles. And it gives sustained drug release for a period of 40 days in vitro with a Fickian diffusion mechanism.

[82]

Doxycycline

α-methoxy-ω-amino-poly (ethylene glycol), N, N, dimethylformamide (DMF)

Mineralized doxycycline nanoparticles manufactured with block copolymer that provides drug release with pH sensitivity. Template mineralized with calcium carbonate. At normal pH of gingival drug release from nanoparticles retarded due to mineral structure, but in acidic pH of gingiva which occurs due to bacterial biofilm provides controlled release of antibiotics.

[83]

Curcumin

Polyethylene glycol (PEG) 400, sodium lauryl sulfate (SLS), tri-ethanol amine (TEA), pluronic 127, carbopol P 934, propylene glycol (PG)

1% w/v of carbopol P 934 and 30% w/v of pluronic F127 give a double response (pH sensitive and thermoresponsive) in one system. The formulation which contains 2% curcumin gives the most accepted results related to pH, gelling temperature, and controlled release of drugs for long periods.

[76]

Secnidazole, serratiopeptidase

Alginate/HPMC, propylene glycol

In situ gel system formulated by using alginate with hydroxyl propyl methyl cellulose and secnidazole-serratiopeptidase, which provides controlled release of drugs for more than 10 h

[84]

Metronidazole

Gellan gum, thioglycolic acid

Esterification of gellan gum with thioglycolic acid provides thiol conjugation. Conjugation of gellan-thioglycolic acid characterized by decreased sensitivity of gellan gum to cation-activated gelation. And mucoadhesive property increased due to thiolation.

[85]

Doxycycline HCL

Sodium alginate, HPMC, mannuronic acid, guluronic acid, human serum with calcium

The formulation consists of alginate and HPMC with the function of gel former and viscosity enhancer respectively. A similar composition to GCF, that is serum, provides sol-gel phase transformation upon mixing. The formulation provides sustained drug release over a period of 12 days.

[86]

–

Carboxymethyl chitosan (CMCS), chitosan, glycidyl methacrylate dimethyl sulfoxide (DMSO)

Developed a system with biodegradable polymer and photo-initiator: visible light lamp (420–480 nm). The gelation time of formulation decreased by photo-initiator.

[87]

–

PEG possessing sulfanyl groups at both ends (SHPEG-SH), methanol and chloromethyl styrene (CMS)

Saita et al. successfully developed a redox injectable gel and applied it to the rat associated with periodontitis. And the result was sustained release of drug from the gel, oxidative damage reduced in periodontal area, and gingival blood flow recovery, which was due to ROS scavenging activity of redox injectable gel in the periodontal area. Additionally, P. gingivalis inhibited by RIG and bone loss prevented.

[88]